Summary of the article: -Hypertension is one of the most common cardiovascular morbidities. Causes can be classified according to the onset either immediately post-transplant, early or late. -Immediately after the transplant may be due to induction IS drugs, rebound hypertension, hypervolemia or inadequate pain control. -Early onset may be due to steroids, renal artery stenosis or CNI’s. -Late onset may be due to chronic allograft dysfunction or failing native kidneys. Antihypertensive medications used: -Calcium channel blockers (dihydropyridine or non-dihydropyredine) -B-blockers -alpha 1 blocker -Diuretics -ACEI or ARBS Management of post-transplant hypertension in my center -The treatment of immediate post-transplant hypertension is done through nitroglycerin infusion, CCBs (dihydropyridine based-amlodipine), B blockers and diuretics in cases of hypervolemia/pulmonary congestion or edema. -The Use of non dihydropyredine in cases associated with low drug levels. -Alfa blockers are used in cases of associated with prostatic enlargement or as add on drug. -ACEI or ARBs in cases associated with proteinuria (diabetic nephropathy or on mTori or those with chronic allograft nephropathy with acceptable eGFR).
Wee Leng Gan
2 years ago
Hypertension is one of the most common comorbid among renal transplant recipient especially those with history of diabetes mellitus, hyperlipidemia, and obesity.
The pathogenesis of post-transplant hypertension is complex and is multifactorial. Post-transplant hypertension can be divided into immediate, early, and late post-transplant periods.
Volume overload from intravenous fluid administration is common during the immediate post-transplant period and commonly contributes to hypertension seen early after transplantation.
Immunosuppressive medications and donor kidneys are associated with post-transplant hypertension occurring at any time point after transplantation.
Transplant renal artery stenosis and obstructive sleep apnea (OSA) are recognized causes of resistant hypertension post-transplantation.
Blood pressure (BP) targets and management involve both non-pharmacologic and pharmacologic treatment ; preferably CCB , betablocker, diuretic avoid ACE/ ARB. and should be individualized. BP of <130/80 mmHg is a reasonable target. Similar to complete renal denervation in non-transplant patients, bilateral native nephrectomy s another treatment option for resistant post-transplant hypertension.
Further research needed for evidence for the pathogenesis of post-transplant HTN and guide clinicians on the appropriate BP measurement method, use of antihypertensive medications, surgical or procedural interventions, and establish BP targets for kidney transplant recipients.
Batool Butt
2 years ago
Kidney transplantation is the treatment of choice for advanced chronic kidney disease unless contraindicated .Cardiovascular morbidity and mortality remain high after transplantation. Major and important risk factor for CVD is Hypertension- one of the leading cause of CKD and accounts for about 24-90% post transplantation. Also associated with metabolic diseases, such as diabetes mellitus, hyperlipidemia, and obesity. Hypertension can be classified into persistent , Recovered hypertension ,persistent normotensive and Post transplant Hypertension. Target blood pressure should be <130/90mmHg in kidney transplant patients according to ACC/AHA guidelines. Post transplant hypertension is defined as elevated BP persistently with the use of antihypertensive medications after kidney transplantation. Post transplant hypertension can further be categorized based on time of presentation.
1) Immediate post transplantation can be because of Hypervolemia during the surgery, heavy doses of steroids,Rebound Hypertension and Inappropriate Pain Management
2) Early post-transplant hypertension can be due to drugs(CNIs, steroids)and TRAS.
3) Late post-transplant-due to Chronic Renal Allograft Dysfunction,Fibroblast Growth Factor (FGF) 23 and Obstructive Sleep Apnea BLOOD PRESSURE MANAGEMENT OF POST RENAL TRANSPLANT PATIENT.
Non-pharmacologic interventions are similar to other types of patients –adopt lifestyle changes like modification in diet, exercise at least five times a week , and stress reduction, and smoking cessation.
Pharmacological management of post renal transplant hypertension
1) Diuretics-loop diuretic( In case of volume overload with peripheral edema and pulmonary congestion)
Thiazide diuretic (CNIs salt sensitivity hypertension ),Mineralocorticoid receptor antagonist (anti-proteinuric effect and cardiovascular benefits )
2) Beta blocker-most common anti-hypertensive drugs-reduce sympathetic effect and decrease pro-inflammatory cytokines but cause masking of hypoglycemic symptoms
3) Calcium channel blocker- a preferred first line antihypertensive agent for kidney transplant recipients if no contraindication -act as a vasodilator to counter the vasoconstrictive effect of CNIs and prevent post-transplant acute tubular injury (ATI) or DGF.
4) ACEIs and ARBs-not to be used in early post transplant period as chances of hyperkalemia and worsening of graft function.it has additional effect in reducing proteinuria and cardiovascular benefit.
5) Alfa 1 antagonist-to be used along with other anti-hypertensives , not a potent drug.
6) Alpha 2 agonist-major side effect is rebound hypertension when abruptly stopped.
Surgical Management: in cases of resistant and refractory hypertension .Native nephrectomy ,Native renal sympathetic denervation, Catheter ablative sympathetic denervation How do you manage hypertension after kidney transplantation in your workplace?
Non-pharmacological management at our center is almost the same ,however pharmacological treatment includes-first line calcium channel blocker(amlodipine) followed by beta blocker (bisoprolol or labetolol),then alpha blocker or vasodilator like hydralazine .Loop diuretic are only given in cases of volume overload.In cases of hypertensive emergency-first line is labetolol and with angina symptoms nitrates.
Nazik Mahmoud
2 years ago
Post kidney transplant hypertension is a common medical problem ,it divided into three groups according to the time of diagnosis ;immediate ,early and late
the main cause of immediate is fluid overload and pretransplant hypertension
the early group risk factors had relation with drugs like CNI and predinsilone,the late presentation represents chronic allograft failure or renal artery stenosis
so the diagnosis could be office measurement or ambulatory 24 hr measurement
Mangment start by life style modifications,diet control and then pharmacological treatment,drugs used in mangment are calcium Chanel blockers,dirutics ,beta blockers
in our center we used same way of treatment
Amna Khalifa
2 years ago
Briefly summarise this article
Kidney transplant is best mode of RRT, it improves survival & quality of life.
With calcineurin inhibitors (CNI) in the 1980’s short-term renal allograft survival has greatly improved
Several immunological and non-immunological causes contribute to long-term renal and patient survival outcomes.
Similar to non-transplant patients, cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality in kidney transplant recipients (4). Hypertension (HTN) is a usual finding in this population and one of the most common risk factors for CVD (5).
review the pathogenesis of posttransplant HTN,
including transplant renal artery stenosis (TRAS)
and differing management options based on the etiology of hypertension in different clinical transplant recipient scenarios.
Determining when non-pharmacological interventions, including transplant renal artery angioplasty and/or stenting, bilateral native nephrectomy, and native renal denervation (RDN), are appropriate will also be discussed.
EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION
The greater incidence of post-transplant hypertension maybe related to the introduction of cyclosporine
A study in Spain looked at patients transplanted in three different years (1990 vs. 1994 vs. 1998) and noted a progressive increase in the incidence of post-transplant HTN with subsequent years for all those three periods. The number of antihypertensive medications required in more recent transplants also increased compared to patients who were transplanted earlier (9).
Overall prevalence of post-transplant HTN has ranged from 24 to 90% DEFINITION OF POST-TRANSPLANT HYPERTENSION
Post-kidney transplant HTN can be defined as a
1. persistently elevated BP or
2. normotension with use of antihypertensive medications after successful kidney transplantation
posttransplant HTN with different cutoff levels are reported as 140/90 or 145/95 or 150 /90 in different studies
In addition to the defining normal BP levels, the presence or absence of HTN during the pre-kidney transplant period may further categorize kidney transplant recipients into four groups:
1. persistent HTN, occurs in patients with HTN both in the pre- and posttransplant periods. Incidences 40%
2. recovered HTN, have HTN only during the pre- but not the post-transplant period. Incidences 28%.
3. persistent normotension, patients have no history of HTN preceding transplant and remain normotensive post-transplant. Incidences 13%.
4. post-transplant HTN. develops de novo HTN after kidney transplant incidences 19%.
In this review, post-kidney transplant HTN refers to persistent and post-transplant (de novo) HTN unless otherwise specified.
The European Society of Hypertension and the European Society of Cardiology guidelines defined isolated Systolic HTN in the general population as SBP ≥140 and DBP <90 mmHg (20). Similar to elderlies
Pathogenesis of isolated systolic HTN involves in both intrinsic alterations resulting from
1-normal aging process
2-development of modifiable risk factors leading to increased arterial stiffness . Diastolic HTN is defined as DBP of ≥90 mmHg, with a SBP 130 or DBP >80 mmHg .
A recent 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a target BP of <130/80 mmHg. More than this will be defining the hypertensive post kidney transplant. PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION
Identifying initial occurrence of post-transplant HTN can narrow the differential diagnosis for the etiology and can tailored therapy. 1-Immediate Post-transplant Period
During this time, post-transplant HTN is generally a result of external factors like transplant surgery, IV fluids, and high doses of steroids. Peri-transplant Hypervolemia
IV fluid given during surgery and in the immediate postoperative period can lead to hypervolemia, particularly in patients with delayed graft function (DGF). A single center cross-sectional study showed that the prevalence of hypervolemia measured by multifrequency bioimpedance analysis for extracellular fluid in stable kidney transplant recipients was 30%, and up to 5% had severe hypervolemia. This study showed that hypervolemia was significantly associated with elevated systolic, diastolic, and mean arterial pressures. Several indicators can be used to estimate volume status.
These include
· conventional measurements such as BP, heart rate, urine output, central venous pressure, and pulmonary artery pressure.
· non–conventional measurements such as intraoperative transesophageal echocardiography , non-invasive dynamic cardiac output technology, e.g., pulse contour analysis, pulse wave transit time, thoracic electrical bioimpedance/bioreactance, and carbon dioxide rebreathing technologies. These are not readily available. High-Dose Steroids
· Causing alterations in intrinsic pressor response leading to arterial vascular resistance
· Might be responsible for HTN during immediate post-transplant period.
Rebound Hypertension
Medications Such as B blockers and clonidine. Inappropriate Pain Management 2-Early Post-transplant Period
systolic HTN (≥140 mmHg) occurred at the mean duration of 26–50 weeks after kidney transplantation, while the baseline renal allograft function and stable dose of maintenance immunosuppressive medications are generally reached around 3–6 months post-transplant. Weight Gain
Between 6- and 12-months post-transplantation, weight gain commonly occurs, Obesity (BMI ≥ 30 kg/m2) after kidney transplantation is significantly associated with post-transplant HTN
Positive fluid intake from intra-and post-operative IV fluid is a common cause of weight gain, However, after regaining renal allograft function, urinary excretion of the fluid gain can mobilize sodium and water. This can partly help to control BP. Calcineurin Inhibitors
There are two main mechanism of CNI-induced post-transplant HTN resulting from interfering vascular tone and renal sodium transport handling.
· Renal vasoconstriction. mediated by endothelin rather than angiotensin 2.
· Renal vasodilation. Impaired vasodilation is a result of CNI induced reduction of nitric oxide, a vasodilator. CNIs inhibit inducible nitric oxide synthase in vascular smooth muscle cells
· Increased renal sodium transport handling Steroids Hypertensive Donor Kidney Transplant Renal Artery Stenosis (TRAS) 3-Late Post-transplant Period Chronic Renal Allograft Dysfunction Fibroblast Growth Factor (FGF) 23 Obstructive Sleep Apnea OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
Cardiovascular Outcomes-Related to Post-transplant Hypertension, During the post-transplant period, elevated BP is associated with poorer renal allograft and patient outcomes.
HTN is one of the most important risk factors for heart failure, particularly heart failure with preserved ejection fraction (HFpEF). Uncontrolled HTN after kidney transplantation leads to structural damage to both the renal allograft and heart eventually resulting in decreased renal and cardiac functions. BLOOD PRESSURE MANAGEMENT pharmacological and non pharmacological
Others include native nephrectomy
Native Sympathetic denervation and Catheter Ablative Renal Denervation
in our practice
we exclude dehydration or over hydration , then we initiate anti-hypertensives including ACE and calcium channel blockers
Fatima AlTaher
2 years ago
Definition of hypertension after kidney transplantation is still controverse , while ACC/AHA define HPN in general non transplantation population as systole >130 and diastole>80 mmhg and defind isolated systolic HPN as systole > 140 while diastole <90 which is common in elderly population mainly due to arterial stiffness while isolated diastolic HPN refers to diastole > 90 mmHg while systole is <140 that is more common in young ,obese patients with sedentary life , but in transplant population no definite cut off levelto define HPN but most investigators consider level >130/80 mmHg as HPN .
Posttransplantation HPN can be classified according to either A) onset time : it can be classified into 1) immediate onset : usually caused by volume overload, effect of induction IS , in adequate pain control, rebound HPN of the pre transplant HPN 2) early onset : wt gain , drug effect specially steroid and CNI . 3) late onset : usually it’s drug induced transplant nephropathy, transplant renal artery stenosis, increase fibroblast growth factor 23 , sympathetic over activity and native kidneys induced HPN or other causes. B) According to HPN status before transplantion, post transplantion HPN can be further devided into 1) Persistent HPN:
refers to HPN that excite pre and post transplant 2) recoverd HPN :
HPN present pre but not post transplant 3) persistent norm tension :
no HPN , neither pre nor post transplant 4) post transplant HPN :
dono vo HPN that start after transplantion and was not present pre transplant.
Drug effect specially steroid and CNI , Hypertensive donor , transplant artery stenosis Transplant renal artery stenosis (TRAS)
is a common vascular complications in kidney transplantion affecting 1-23% of patients and is responsible for upto 5% of cases of post transplant HPN. It’s caused by interaction between immunological and non immunological causes 2- Non immunological causes : vascular injury during transplant operation, presence of vascular disease in donor or recipient, atherosclerosis, CMV infection. 2- Immunological causes as
Immune complex mediated endothelial injury Clinical presentation of TRAS :
– unexplained deterioration of kidney function.
– generalized odema due to renal ischemia that activate RAS system Investigations
1- duppler US on renal vessels : non invasive, can diagnose presence and severity of TRAS , but it’s operator dependant
2- Renal artery CT : risk of contrast nephropathy is present.
3- MRA.
4- Carbon dioxide (CO2) angiography. Treatment of TRAS
1- pharmacological treatment: ACEI or ARBS + diuretics
2- Renal artery angioplasty and stent insertion.
3- surgical revascularization.
Out come of HPN after kidney transplantation
pre transplant HPN can affect patient and graft survival where lower diastolic BP is associated with better survival.
Post transplant HPN inversely affect graft and patient survival and increase associated CV risk Management of post transplantion HPN
1- non pharmacological measures ,: stop smoking , regular exercise, low salt diet .
2- Drug therapy including CCB , BB and diuretics Treatment of refractory post transplant HPN
1- Native nephrectomy
2- Bilateral renal sympathetic denervation .
B) Treatment of HPN in kidney recipient n my institution
1- In mild HPN : -During early post operative period :
Revise volume status , adequate pain control , psychological support and sometime we had to use low dose anyxolytic drugs.
-After longer time from transplantation
We start with revising patient diet specially salt intake, volume status and smoking and life style modification . If no improvement or HPN progressed to higher level ,we consider drug therapy starting with CaCB, BB and centrally acting drugs
Alyaa Ali
2 years ago
Epidemiology of post transplant hypertension
Prevelance is 24 to 90%.
Definition of post transplant HTN
Post transplant HTN is a persistent elevation of BP or normotension with use of antihypertensive medications after successful kidneytransplantation.
Post transplant HTN is persistent HTN or denovo post transplant HTN.
SBP > 140, DBP > 90 mmHg.
Pathogenesis of post transplant hypertension
1. Immediate post transplant period
Peri transplant hypervolemia
Induction immunosuppressive medications ( high dose steroids)
Rebound hypertension due to abrupt discontinuation of antihypertensive therapy in pre transplant BP medications to avoid early hypotension especially B blockers or clonidine.
Inadequate pain control.
2. Early post transplant
Weight gain
Calcineurin inhibitors
Steroids
Hypertensive donor kidney
Transplant renal artery stenosis
3. Late post transplant
Chronic renal allograft dysfunction
Obstructive sleep apnea
Fibroblast growth factor 23
Failed native nephrectomy
Sympathetic overactivity
Outcomes of HTN after kidney transplantation
Elevated BP is associated with poorer renal allograft and patient Outcomes.
HTN is one of the most important risk factors for heart failure,
especially heart failure with preserved ejection fraction.
Patients with LVH or HFpEF have increased morbidity and mortality and are at high risk for cardiac related events.
BP measurement
A 24 hours ABPM though the gold standard, is inconvenient and not widely utilized.
Home blood pressure monitoring
Office blood pressure recording
Blood pressure management
1. Lifestyle modifications as diet, exercise and stress reduction are required for all patients.
2. Pharmacological therapy
Choice of medications depending on patient’s characteristics, tolerability and medication side effects ( diuretics, CCB,BB, Renin angiotensin aldosterone system blockade , Alpha1 antagonists or Alpha 2 agonists).
3. Procedural or surgical interventions
Transplant renal artery stenosis: Transplant renal artery angioplasty +/- stenting.
Obstructive sleep apnea: CPAP
Failed native nephrectomy: bilateral native nephrectomy
Sympathetic overactivity: native renal denervation
Hinda Hassan
2 years ago
This is a review of post-transplant hypertension epidemiology, pathogenesis, specific etiologies. cardiovascular and survival outcomes, medications, guidelines and non-pharmacological interventions DEFINITION OF POST-TRANSPLANT HYPERTENSION:
Is a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation. the cut values are less than 140/90 in most of studies.
It is classified according to presence or absence of HTN during the pre-kidney transplant period into four groups: persistent HTN, recovered HTN, persistent normotension, and post-transplant HTN.
1- Persistent HTN occurs in patients with HTN both in the pre- and posttransplant periods,
2- recovered HTN have HTN only during the pre- but not the post-transplant period.
3- Persistent normotensive patients have no history of HTN preceding transplant and remain normotensive post-transplant.
4- Post-transplant HTN requires developing de novo HTN after kidney transplant.
Another entity is isolated forms of HTN both systolic and diastolic. The former is the most common phenotype of HTN in elderly patients and the latter occur in younger, sedentary individuals with a higher body mass index (BMI)
PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION:
Post-transplant hypertension can be divided into immediate, early, and late post-transplant periods. Each has different pathogeneses. 1- Immediate :
Peritransplant hypervolemia
Induction medications
Rebound HTN
Inadequate pain control 2- Early:
Weight gain
CNI
Steroid
Hypertensive donor kidney
Transplant renal artery stenosis 3- Late post-transplant
Chronic renal allograft dysfunction
Fibroblast growth factor 23
OSA
Failed native kidney
Sympathetic over activity OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION:
Several studies have demonstrated an association between post-transplant HTN and renal allograft failure. HTN can lead to heart failure with preserved ejection fraction and renal patients has increased tendancy of LVH. kidney transplant recipients with either of these have increased morbidity and mortality and are at high risk for cardiac-related events. Uncontrolled HTN after kidney transplantation leads to structural damage to both the renal allograft and heart eventually resulting in decreased renal and cardiac functions. BLOOD PRESSURE MEASUREMENT
Reliable BP measurement can be standardized with the following definitions:
-office blood pressure :the mean of three non-invasive BP measurements is referred to as
-home blood pressure monitoring :recording at least twice the daily average of two home blood pressure readings over a minimum of 4 days
-24h ambulatory blood pressure monitoring : requires wearing an electronic blood pressure measurement device to record and averages multiple readings over a 24h period BLOOD PRESSURE MANAGEMENT 1- Lifestyle modifications: Diet, Exercise and Stress reduction 2- Pharmacological therapy: Diuretics , Calcium channel blockers, Beta-blockers, RAS blockade ,Alpha1-antagonists andalpha2 agonists 3- Procedural or surgical interventions: Transplant renal artery angioplasty ± stenting , Continuous positive airway pressure , Bilateral native nephrectomy and Native renal denervation in Sudan, we depend mainly on office blood pressure measuring and we use medications according to international guidelines.
Dalia Ali
2 years ago
Introduction
Hypertension is one of the most common cardiovascular co-morbidities after successful kidney transplantation. It commonly occurs in patients with other metabolic diseases, such as diabetes mellitus, hyperlipidemia, and obesity. The pathogenesis of post-transplant hypertension is complex and is a result oftheinterplaybetween immunological and non-immunological factors. Post-transplant hypertension can be divided into immediate, early, and late post-transplant periods. This classification can help clinicians determine the etiology and provide the appropriate management for these complex patients. Volume overload from intravenous fluid administration is common during the immediate post-transplant period and commonly contributes to hypertension seen early after transplantation. Immunosuppressive medications and donor kidneys are associated with post-transplant hypertension occurring at any time point after transplantation.
This article will review the pathogenesis of posttransplant HTN, including transplant renal artery stenosis (TRAS) and diering management options based on the etiology of hypertension in dierent clinical transplant recipient scenarios. Determining when non-pharmacological interventions, including transplant renal artery angioplasty and/or stenting, bilateral native nephrectomy, and native renal denervation (RDN), are appropriate will also be discussed.
EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION
Depending on the definition and methods of blood pressure (BP) measurement utilized, the prevalence of post-transplant HTN has been widely reported, and it has generally increased over time. This greater incidence of post-transplant hypertension maybe related to the introduction of cyclosporine (CsA).A study in Spain looked at patients transplanted in three dierent years (1990 vs. 1994 vs. 1998) and noted a progressive increase in the incidence of post-transplant HTN with subsequent years for all those three periods. The number of antihypertensive medications required in more recent transplants also increased compared to patients who were transplanted earlier . Overall prevalence of post-transplant HTN has ranged from 24 to 90%
DEFINITION OF POST-TRANSPLANT HYPERTENSION
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation. However, the main question that remains is what is a normal BP level? Dierent studies have defined posttransplant HTN with dierent cutolevels for systolic and diastolic blood pressure (SBP and DBP) and dierent requirements for the use of antihypertensive medications.
Isolated forms of HTN both systolic and diastolic still occur after kidney transplantation. The European Society of Hypertension and the European Society of Cardiology guidelines defined isolated systolic HTN in the general population as SBP 140 and DBP <90 mmHg (20). This is the most common phenotype of HTN in elderly patients
PATHOGENESISOFPOST-TRANSPLANT HYPERTENSION -Immediate Post-transplant Period
During this time, post-transplant HTN is generally a result of external factors like transplant surgery, IV fluids, and high doses of steroids.
–Early Post-transplant Period
1-Weight Gain
2-Calcineurin Inhibitors
3-Steroids
4-Hypertensive Donor Kidney
5-Transplant Renal Artery Stenosis (TRAS)
–Late Post-transplant Period
Apart from the above-discussed factors contributing to HTN in the early post-transplant period, some factors may contribute to HTN in the late post-transplant period.
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
Pre-transplant BP is associated with renal allograft and patient survival outcomes after kidney transplantation. Very low pretransplant SBP (<110 mmHg) and DBP (<50 mmHg) are associated with a decrease in renal allograft loss. Specifically during dialysis lower pre- and post-dialysis DBP are associated with better patient survival post-transplantation
Cardiovascular Outcomes-Related to Post-transplant Hypertension
HTN is one of the most important risk factors for heart failure, particularly heart failure with preserved ejection fraction (HFpEF) (124). Kidney transplant recipients with left ventricular hypertrophy (LVH) or HFpEF have increased morbidity and mortality and are at high risk for cardiac-related events. Both pressure and volume overload contributed to LVH, which is further exacerbated by age, genetic factors, vascular hemodialysis access, dialysis vintage, diabetes, and blood pressure
BLOOD PRESSURE GUIDELINE FOR KIDNEY TRANSPLANT RECIPIENTS
BP targets have been a controversial topic not only in the nontransplant population but also in kidney transplant recipients. Several professional societies from different countries have created clinical practice guidelines with some similaritiesand differences . Until there is strong clinical outcome evidence in terms
of CV, patients, or renal allograft survival, BP targets should be individualized, taking into account immunologic and nonimmunologic factors that are contributing to HTN in each kidney transplant recipient.
CONCLUSIONS
HTN is a very common disease inCKD and ESRD and remains so after kidney transplantation. The pathogenesis ofpost-transplant HTN is complex. BP measurement is still the main barrier to accurately diagnose and follow-up in HTN management. A 24-h ABPM, though the gold standard, is inconvenient and not wildly utilized. The choice of antihypertensive medication requires the clinician to take transplant and immunological factors into the consideration. Management for OSA and interventions for resistant HTN, such as transplant renal artery angioplasty ± stenting, bilateral native nephrectomy, and native RDN, remain options for resistant HTN in selected kidney transplant recipients. There is no conclusive BP target for this population and therapy targets need to be individualized. Further research to develop a stronger body of evidence for the pathogenesis of post-transplant HTN and guide clinicians on the appropriate BP measurement method, use of antihypertensive medications, surgical or procedural interventions, and establish BP targets for kidney transplant recipients.
In our center
1-focus on modification of life styles
2-encourage for daily exercise
3-decease steroid dose if possible
4-if no benefits we use the pharmacological methods
Ahmed Omran
2 years ago
Hypertension is one of the major factor causing cardiovascular co-morbidities.
It is common that hypertension persists even following kidney transplantation in immediate and late post transplant period. Its prevalence has increased after the beginning of use of calcineurin inhibitors.
Post kidney transplant hypertension is divided into three main groups depending on the onset of hypertension ;immediate, early and late.
There are no consensus guidelines for defining post transplant hypertension but there are studies which have tried defining post transplant hypertension. Their range varies from SBP > 140-150 and DBP > 90-95 mm Hg.
Post transplant hypertension has also been classified further in 4 groups depending on presence or absence of pre transplant hypertension :persistent hypertension ,recovered hypertension ,persistent normal Bp, and post-transplant hypertension.
The pathogenesis of post transplant hypertension is different according to the time of occurrence of kidney transplant :early post transplant period has not been defined but on the basis of time of stable dose of maintenance immunosuppression it is considered to be between 24-52 weeks post transplantation.:
-Immediate post transplantation – hypervolemia, induction immunosuppression, rebound hypertension and inadequate pain control-
Early post transplantation – weight gain, CNI, steroids, hypertensive donor kidney and TRAS
-Late post transplantation – Chronic allograft dysfunction, FGF23, OSA, failed native kidneys and sympathetic overdrive.
The higher is the post transplant hypertension, the higher the chance of renal allograft failure. BPs as low as SBP<110 and DBP< 50 are associated with decreased renal allograft lost.
HTN management includes lifestyle modification, pharmacological therapy and surgical interventions ;native nephrectomy and renal sympathetic denervation.
This article explains post transplant hypertension in satisfactory depth and could be very informative and practical..
Asmaa Khudhur
2 years ago
1-Briefly summarise this article
Approach and Management of Hypertension After Kidney Transplantation
EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION
The prevalence of post-transplant HTN has been widely recorded and, depending on the criteria and techniques of blood pressure (BP) measurement used, it has generally risen over time. The introduction of cyclosporine (CsA) may have contributed to the higher frequency of post-transplant hypertension. From 24 to 90% of people had post-transplant HTN overall.
DEFINITION OF POST-TRANSPLANT HYPERTENSION
after kidney replacement After a successful kidney transplant, HTN is characterized by persistently increased blood pressure or normotension with antihypertensive drug use.
In addition to defining normal blood pressure levels, the presence or absence of HTN in the time before a kidney transplant may further divide kidney transplant recipients into four groups: post-transplant HTN, persistent HTN, recovered HTN, and persistent normotension.
Patients with persistent HTN experience HTN both before and after transplantation, whereas those with recovered HTN only experience HTN before transplantation and not after. Patients with persistent normotension have no history of HTN before transplant and continue to have normal blood pressure after transplant. After a kidney transplant, de novo HTN must occur in order to have post-transplant HTN.
After a kidney transplant, isolated forms of HTN, both systolic and diastolic, continue to exist.
A suitable definition of HTN in post-transplant recipients may be BP 130/80 mmHg.
PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION
common factors contributing to post-transplant hypertension during three different periods.
Immediate Post-transplant Period
peri-transplant hypervolemia.
Induction immunosuppressant medication
Rebound hypertension
Inadequate pain control.
Early Post-transplant Period
weight gain
Calcineurin inhibitors
Steroid
Hypertensive donor kidney
Transplant renal artery stenosis
Late Post-transplant Period
chronic renal allograft dysfunction
Fibroblast growth factor 23
Obstructive sleep apnea
Failed native kidneys
Sympathetic overactivity.
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION :
Pre-transplant blood pressure is linked to renal allograft and post-kidney transplant patient survival rates. Renal allograft loss is decreased by very low SBP (110 mmHg) and DBP (50 mmHg) levels prior to transplant. Lower pre- and post-dialysis DBP, in particular, is linked to improved patient survival after transplantation .
Elevated blood pressure is linked to worse renal allograft and patient outcomes in the post-transplant period. However, as was already mentioned, there are a number of renal allograft injuries that are linked to post-transplant HTN.
Cardiovascular Outcomes-Related to Post-transplant Hypertension:
One of the main risk factors for heart failure, especially heart failure with preserved ejection fraction (HFpEF), is high blood pressure (HTN) .Patients undergoing kidney transplantation who have LVH or HFpEF have a higher risk of morbidity and death as well as cardiac-related complications. Both pressure and volume overload played a role in LVH, which was made worse by age, genetics, vascular hemodialysis access, dialysis vintage, blood pressure, diabetes, and other conditions.
BLOOD PRESSURE MANAGEMENT
Non-pharmacological measures :
Non-pharmacologic interventions, such as diet, exercise, and stress reduction, should always be part of treatment of HTN.
Pharmacological measures:
Use of Antihypertensive Medications
Diuretics, Loop Diuretics, Thiazides,
Mineralocorticoid Receptor Antagonists
Beta-Blockers
Calcium Channel Blockers
Angiotensin-Converting Enzyme Inhibitors
(ACEI) and Angiotensin II Receptor
Blockers (ARB)
Alpha1-Antagonists
Alpha2 Agonists
OTHER MANAGEMENT FOR BLOOD PRESSURE
Native Nephrectomy
Native Renal Sympathetic Denervation
Surgical Renal Denervation by Bilateral
Native Nephrectomy
Catheter Ablative Renal Denervation
2-How do you manage hypertension after kidney transplantation in your workplace?
By changing lifestyle
Non-pharmacological measures and pharmacological measures.
Nasrin Esfandiar
2 years ago
Q1- Introduction: A very common and complex pathology after the transplantation is Hypertension which can be caused by a lot of nonimmunological and immunological factors that are collateral for transplantation. Transplant renal artery stenosis (TRAS), dyslipidemia, medication effects, in particular, CNI, metabolic syndrome, OSA, obesity, DM can cause high cardiovascular risk and effect the graft survival. Also, post-transplant hypertension, usually associated with chronic graft dysfunction, being classified as early, immediate and late after TX. The article goes through pathogenesis of hypertension post-transplantation, its causes, classification and the treatment options including interventional angioplasty and pharmacological or native kidney nephrectomy and renal denervation in the type of hypertension which shows resistance, based on the evidence available in the guideline. Definingpost-transplantation: The meaning and the prevalence Of HTN post-transplantation vary in different studies. However, target Bp has the condition of being less than 130/80 Persistent high blood pressure or normotensive with medications post-transplantation. Other classifications of hypertension include: persistent normotension, persistent HTN, recovered HTN, and post TX HTN, with aging isolated systolic HTN. In addition, common, Post-transplant HTN associated with increased CVS morbidity is in our list.
HTN after the transplantation: IVF peri-and postoperative time can cause Immediate post-transplant period, leading to induction immunosuppression medications such as steroids accompanied with increased sympathetic over activity, volume overload, deficient pain control also due to sympathetic overactivity, and rebound HTN especially those on BB.
Early post-transplantation: Between 24-52 weeks post-TX, having many factors involved:
immunosuppression therapy (CNI, STEROIDS), Weight gain, hypertensive kidney donor, transplant RAS CNI Induced HTN: Change of Vascular tone, with arteriolar vasoconstriction and reduced vasodilator Late post-transplantation: OSA, Sympathetic overactivity, Chronic allograft dysfunction, Failed native kidneys, FBGF23, RAS, renal artery stenosis Q2- Fluid management if overload, calcium channel blockers like dilthiazem and so on.
Jamila Elamouri
2 years ago
Briefly summarise this article
Hypertension (HTN) is a usual finding in transplant patients and one of the most common risk factors for CVD. After kidney transplantation, the most common cardio-vascular co-morbidities is hypertension. EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION
This greater incidence of post-transplant hypertension may be related to the introduction of cyclosporine (CsA). Overall prevalence of post-transplant HTN has ranged from 24 to 90%. The number of antihypertensive medications required in more recent transplants also increased compared to patients who were transplanted earlier. DEFINITION OF POST-TRANSPLANT HYPERTENSION
It is a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation. different studies defined HTN with different cutoff levels for systolic and diastolic blood pressure. In addition to definition of normal blood pressure, the presence or absent of HTN in the pre- and post-transplant period may further categorized in to four categories:
1- Persistent HTN: HTN present in both pre- and post-transplant periods.
2- Recovered HTN: HTN only during pre- but not the post-transplant period.
3- Persistent normotensive patients have no history of HTN before transplant and remain normotensive post-transplant.
4- Post-transplant HTN requires developing de novo HTN after kidney transplant.
HTN is defined isolated systolic HTN in the general population as SBP ≥140 and DBP <90 mmHg.
In elderly patients the systolic BP is usually increased while diastolic BP decrease. The pathogenesis involves both intrinsic alterations resulting from normal aging process accompanied by development of modifiable risk factors leading to increased arterial stiffness. While, diastolic HTN is defined as DBP of ≥90 mmHg, with a SBP <140 mmHg, and is more common in younger, sedentary individuals with a higher body mass index (BMI).
SPRINT demonstrated cardiovascular (CV) benefits of tighter BP control leading to new BP guidelines and re-defined HTN for the general population as systolic blood pressure (SBP) >130 or DBP >80 mmHg. But the definition of HTN in kidney transplant recipients remains controversial.
PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION
There is different pathogenesis in the development of HTN in transplant recipient.
Immediate Post-transplant Period:
HTN in this period is generally a result of external factors like transplant surgery, IV fluids, and high doses of steroids.
C- Late post-transplantation
· Chronic renal allograft dysfunction
· Fibroblast growth factor 23
· Obstructive sleep apnea
· Failed native kidney
· Sympathetic overactivity.
Calcineurin inhibitors and their role in HTN pathogenesis:
Ø Altered vascular tone
They cause both increase in vasoconstriction and impaired vasodilatation.
Ø Altered renal sodium transport handling:
Sympathetic nervous system activation with subsequent sodium retention. OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
Very low pretransplant SBP (<110 mmHg) and DBP (<50 mmHg) are associated with a decrease in renal allograft loss. In dialysis lower pre- and post-dialysis DBP are associated with better patient survival post-transplantation. During the post-transplant period, elevated BP is associated with poorer renal allograft and patient outcomes.
They found that patients with a SBP >140 mmHg at 1 year who were controlled to a SBP ≤140 mmHg at 3 years post-transplantation had improved renal allograft outcomes and reduced CV death compared to those with persistent SBP of >140 mmHg both at 1 and 3 years post-transplantation. Cardiovascular Outcomes-Related to Post-transplant Hypertension
Kidney transplant recipients with left ventricular hypertrophy (LVH) or HFpEF have increased morbidity and mortality and are at high risk for cardiac-related events.
Renal insufficiency is involved in the pathogenesis of HFpEF and causes salt-sensitive HTN. Importantly, a
vicious cycle of cardio-renal dysfunction can result from salt and volume overload. Uncontrolled HTN after kidney transplantation leads to structural damage to both the renal allograft and heart eventually resulting in decreased renal and cardiac function.
BLOOD PRESSURE MEASUREMENT
1- Office blood pressure (OBP)
2- Home blood pressure (HBPM) is a common utilized method of following BP
3- 24-h ABPM
There is good correlation between 24-h ABPM and HBPM than between 24-H ABPM and office blood pressure (OBP).
Elevated day and night SBP obtained from 24-h ABPM were associated with declining renal allograft function, and nighttime elevation is stronger association.
24-h ABPM associated more significantly with graft loss, cardiovascular event and death. Management:
Lifestyle modification regarding diet, exercise, decrease stress. PHARMACOLOGICAL MANAGEMENTS Use of Antihypertensive Medications
Study in Poland found that, Beta-blockers were the most common antihypertensive medication used in this cohort followed by calcium channel blockers. Uses of ACEI, diuretics, and alphablockers were about the same. ARB therapy was utilized least.
BLOOD PRESSURE CONTROL DURING PERI-TRANSPLANT PERIOD Antihypertensive Medications
Volume-overload is a major cause of HTN in CKD and ESRD patients. Volume-dependent HTN is managed with fluid removal during dialysis. Recipient who are about to undergo the transplant surgery are usually left with post-dialysis weight slightly above their established dry weight in an effort to avoid intra- and post-operative hypotension.
ACEI and ARB are generally held following a transplant. An alpha2 agonist like clonidine, however, may need to be continued during peritransplant period to avoid rebound HTN. Most transplant physician chose the antihypertensive medication according to their local common practice. But antihypertensive drugs should be individualized. Diuretics they are not used as first line anti-hypertensive drugs in transplant recipients. As they may cause volume depletion, electrolyte disturbances, and worsening renal allograft function. But they are indicated in special sitting as overload. Loop Diuretics:
Volume control rather than BP control is the indication for loop diuretics in kidney transplant recipients, especially in peri-operative period. During this period the recipient usually given IV fluid in large volume to keep urine output. Volume overload present with peripheral edema, pulmonary congestion, or HTN, diuretics are used to controlled this condition. loop diuretic use has been associated with increased risk
of UTI during the first 5 years after kidney transplantation, because there use depletes medullary NaCl
gradient, which is known to modulate the adaptive and innate immune response.
Furosemide is the most commonly used loop diuretic. It can be used to predict prognosis in AKI (furosemide stress test FST) in non-transplant patients.
Also, in transplant patient furosemide can provide prognostic value as the inadequate response, < 350 ml within 4 h, to a single IV furosemide dose of 1.5 mg/kg given 3 h after renal allograft anastomosis predict increased risk of DGF. The benefit nd risks of their used should be balanced according to patients need. Thiazides
They are used commonly in treatment of HTN in general population, but their used in transplant recipients are uncommon due to their metabolic side effects like hyperglycemia, hyperuricemia, hypercalcemia and hyponatremia.
Thiazides inhibit Na-Cl co-transporter, and may control CNI-induced HTN. Calcium channel blockers, due to their vasodilator effect, are commonly used antihypertensive drugs and are capable of counteract the systemic and renal vasoconstrictive effect of CNI via endothelin. But due to their side effects like peripheral edema and proterinuria, the thiazide are suitable alternative to them for BP control in these cases.
Also, thiazides are good in transplant recipient with hypomagnesemia, especially loop diuretic can worsen it as they can cause magnesium wasting.
CNI and loop diuretics act through the same pathway causing hypomagnesemia, so their combination can cause further urinary magnesium loss.
Thiazides, on the other hand, increase s. Mg when used with CNI. Although, long-term thiazide use may lead to Mg wasting when there is concomitant hypokalemia.
Thiazides may be considered for kidney transplant recipients with CNI-induced salt-sensitive HTN and hypomagnesemia. Mineralocorticoid Receptor Antagonists
They have CV benefits and antiproteinuric effect but are not commonly used in kidney transplant recipients, especially those with impaired renal allograft function. Hyperkalemia is a common side effect that can be worse with CNI-induced hyperkalemia.
One pilot study tests the anti-proteinuric effect of spironolactone, found improvement in the proteinuria by 50%, despite slight decrease in GFR 52 –to-48.
Eplenerone effect on serum potassium had been tested by a study, found slight increase in s. K which was not significant.
Mineralocorticoids are potentially reno-protective by blunting the renal vascular resistance induced by CNI therapy.
With some evidence for antiproteinuric effect and their established safety in transplant recipients even when in combination with ACEI or ARB, MCRA may be a new option for BP control in individual with CNI-induced HTN and proteinuria. beta-blockers
they have cardio-potective effect and survival advantage in general population, dialysis, and transplant recipients as well. Beta-blocker also have additive effect with ACEI and ARB with greater survival in recipients taking this combination. This action don through its effect on sympathetic nervous system as well, its anti-inflammatory effect by decreasing the cytokines which are atherosclerotic mediators. Calcium Channel Blockers
The vasodilatory effect of calcium channel blochers can counteract the vasoconstrictive effect of CNIs and improve BP control. They prevent post-transplant acute tubular injury (ATI) or DGF lower ischemic damage in the renal allograft and reduced CNI nephrotoxicity. Although calcium channel blockers provide better renal allograft function, several studies showed no difference in terms of BP control when using verapamil compared to enalapril or doxazosin. Given the available information, calcium channel blockers remain a preferred antihypertensive agent for kidney transplant recipients barring there are no specific indications for other antihypertensive agents or contraindications to calcium channel blocker therapy.
Dihydropyridine calcium channel blockers can compete with CNI for cytochrome P450 (CYP)3A4 isoenzyme, this leads to increase in both calcium channel blocker and CNI exposure levels. Non-dihydropyridine calcium channel blockers inhibit CYP3A4 isoenzyme and significantly increase CNI level. Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor Blockers (ARB)
ACEIs and ARBs are antihypertensive agents with known antiproteinuric effect. As they decrease GFR at start, it is advisable not use them early post-transplantation to not make confusion regarding graft function. They may be considered in transplant recipients, particularly those with LVH, congestive heart failure, and proteinuria. Alpha1-Antagonists (doxazosin)
They reduce BP by decreasing peripheral vasoconstriction. But they do not used as first line or as a single drug. Alpha1-antagonist may have a role as an adjunctive therapy rather than first line antihypertensive agent in transplant recipients. Alpha2 Agonists
They suppress central sympathetic activity. Specifically, activation of alpha2A receptors causes a sympatho-inhibitory effect and lowers BP. They decrease renal vascular resistance. Two of the oldest alpha2 agonists, methyldopa and clonidine, have long been used for BP control. when used as monotherapy, methyldopa is associated with antihypertensive tolerance, edema, and weight gain. Clonidine is also associated with weight gain and progressive resistance with continued use.
Rebound HTN is common after discontinuation of clonidine, and patients who are on clonidine prior to kidney transplant tend to have uncontrolled HTN resulting from this rebound phenomenon. Therefore, clonidine is rarely used as a single antihypertensive agent following kidney transplantation. OTHER MANAGEMENT FOR BLOOD PRESSURE Native Nephrectomy Native Renal Sympathetic Denervation Surgical Renal Denervation by Bilateral Native Nephrectomy Catheter Ablative Renal Denervation
How do you manage hypertension after kidney transplantation in your workplace?
calcium channel blocker with or with out Beta-blocker are the fist line therapy in general specially in early period.
Mohammed Sobair
2 years ago
Introduction:
Hypertension is common posttransplant. Risk increased in-patient with other risk factors.
Classified as early, immediate and late.
This review the pathogenesis of posttransplant HTN, including transplant renal artery stenosis (TRAS) and differing management options based on the etiology of hypertension. EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION:
Prevalence and incidence, increased overtime, especially with introduction of CNI.
Prevalence of post-transplant HTN has ranged from 24 to 90%. DEFINITION OF POST-TRANSPLANT HYPERTENSION:
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation.
The presence or absence of HTN during the pre-kidney transplant period may further categorize kidney transplant recipients into four groups:
Persistent HTN,
Recovered HTN,
Persistent normotension,
Post-transplant HTN.
Different studies have defined posttransplant HTN with different cutoff levels for systolic and diastolic blood pressure;
Budde et al. >150/90 or using antihypertensive medications except the single use of diuretics.
Malek-Hosseini et al. 145/95 or required antihypertensive medication.
Zeier et al. >140/90 mmHg or antihypertensive treatment.
Kasiske et al. ≥140/90 mmHg.
Campistol et al. SBP ≥140 and/or DSP ≥90 and/or treated with antihypertensive medications.
Until there is stronger evidence of an association between BP level and outcomes in kidney transplant recipients, a BP ≥130/80 mmHg may be a reasonable definition for HTN in this population. PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION:
Immediate Post-transplant Period:
Due to transplant surgery, IV fluids, and high doses of steroids.
Peri-transplant Hypervolemia:
IV fluid given during surgery and in the immediate postoperative period can lead to hypervolemia, particularly in patients with delayed graft function .In addition to CBI ,CAN ,TRAS .FGF23,OSA. OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION:
Poorer renal allograft and patient outcomes.
HTN is one of the most important risk factors for heart failure. Kidney transplant recipients with left ventricular hypertrophy (LVH).
Have increased morbidity and mortality and are at high risk for cardiac-related events. BLOOD PRESSURE MEASUREMENT:
HBPM in conjunction with OBP for our kidney transplant patients to minimize misclassification of HTN diagnosis, monitor possible white coat or masked HTN, and adjust antihypertensive medications. BLOOD PRESSURE MANAGEMENT Non-pharmacologic interventions:
Diet, exercise, and stress reduction. Pharmacological intervention remains the cornerstone of BP control in this population. Renal sympathetic denervation:
Of the native kidneys by either bilateral native nephrectomy or catheter, ablation is also treatment option for resistant HTN in this population.
Additionally, other interventions specific to certain etiologies of resistant HTN, such as transplant renal artery angioplasty ± stenting and treatment for OSA, should be implemented. Guideline for kidney transplant recipients from different scientific medical societies:
KDIGO 2012 (205) ≤130/80.
K/DOQI 2004 (206) ≤130/80
BRA 2011 (209) Clinic blood pressure ≤130/80 125/75 mmHg if urine protein/creatinine ratio (PCR) >50 or ACR>35) (2C) – RAS may be more effective in the minimization of proteinuria but – Used with caution in the first 3 months post-transplant.
CSN Work Group 2014 ≤140/90 regardless of the level of albuminuria ≤130/80 in kidney transplant recipients with Based on comorbidities including DM, stroke, CAD, CCB, recent MI, and CHF – RAS blockers should be avoided in the immediate post-transplantation.
KHA-CARI 2012 guideline (adaptation of the 2009 KDIGO) (212) ≤130/80 in adult – Tighter BP control with BP <125/75 in the patient with proteinuria >1 g/day – Suggests using CCB as the first line antihypertensive agent; however, this should be balance with the patients’ comorbidity and proteinuria. Closely monitor CNI level.
2017 ACC/AHA.
How do you manage hypertension after kidney transplantation in your workplace?
We use CCB in our practice ,late we add ACE or ARB after 3months.
Ahmed Fouad Omar
2 years ago
Summarize the article: Introduction:
Kidney transplantation is still the preferable modality of RRT for CKD patients. CVD is the leading cause of morbidity and mortality post kidney transplantation. HTN is the most common cardio vascular risk factors. It is associated with poor renal allograft and patient outcomes, the overall prevalence in the post-transplant period ranged from 24 to 90%.The pathogenesis is complex and may be related to immunological and non-immunological factors.
Definition and categories of post-transplant hypertension:
Persistently elevated BP ≥130/80 mmHg, or normo-tension with the use of Bp medications after successful kidney transplantation.
Categories:
1. Persistent HTN: both in pre- and post-transplant period (40%)
2. Recovered HTN: only during the pre- and not the post-transplant period (28%)
3. Normo-tension: no HTN pre-transplant, remain normotensive post-transplant(13%)
4. Post-transplant HTN: new HTN after kidney transplant (19%)
Risk factors for post-transplantation hypertension: In the immediate post-transplant period: Inadequate pain control, Hypervolemia, the use of induction immunosuppression and rebound hypertension.
In the early post-transplant period: weight gain, immunosuppressive medication(steroids and CNIs), TRAS.
In the late post-transplant period: chronic allograft nephropathy, sympathetic over activity, failed native kidneys and FGF-23 Blood pressure management options include: Non-pharmacologic measures: life style modification with diet control, encourage exercise, reduce stress. Pharmacological measures (the cornerstone of BP control):
– Calcium channel blockers: dihydropyridine and non-dihydropyridine can be used. non-dihydropyridine CCBs can increase the CNI levels so careful monitoring of CNIs levels should be done.
– Diuretics: They are not the first line of treatment. Loop diuretics are used in volume overload status but they may worsen renal allograft function and cause electrolyte disturbance. Thiazide diuretics can cause metabolic disturbances and hyperlipidemia. Mineralocorticoid antagonists are used mainly in cases of systolic dysfunction but may result in hyperkalemia. – Beta-Blockers: have cardiac protection but there use may mask symptoms of hypoglycemia and thyrotoxicosis, worse lipid profiles and also result in hyperkalemia
– ACEI and ARBs: They have anti-proteinuria and cardio-protection effects. Adverse effects are elevated creatinine, hyperkalemia and anemia. Not the drugs of choice during the immediate and early post-transplant periods as the cause irreversible decrease in GFR and confusion with other causes of renal allograft dysfunction.
– Alpha1-Antagonists, Alpha2 Agonists: not first line of treatment
Procedural or surgical interventions:
Transplant renal artery angioplasty in patients with TRAS
CPAP in patients with OSA
Bilateral native nephrectomy
Native renal denervation
Conclusion:
· No conclusive BP target and target therapy need to be individualized.
· Further research is needed to develop a stronger body of evidence for the pathogenesis of post-transplant HTN and guide clinicians on the appropriate BP measurement method to achieve BP targets for kidney transplant recipients
How do you manage hypertension after kidney transplantation in your workplace?
· We encourage life style modification.
· With regard to pharmacological measures, we start with dihydropyridine CCBs and beta blockers in the immediate post-transplant period. RAAS inhibitors can be added after the stabilization of graft function
· Procedures and surgery are carried as required. We carry TRAS angioplasty with a good outcome. Native nephrectomy if indicated.
Manal Malik
2 years ago
mmaryApproaSuch and Management of Hypertension After Kidney Transplantation Introduction
CVD is a common cause of morbidity and mortality in KTRs. and HTN is the most common risk factor for CVD.
This article will review the pathogenesis of post transplant HTN including Renal Artery Stenosis and different management option based on the etiology of hypertension Epidemiology of post-Transplant HTN
The greater incidence of post-Transplant HTN may be related to cyclosporine
The overall prevalence of post Transplant HTN from 24-90% Definition of post-Transplant Hypertension
Post Kidney Transplant HTN can be defined as a persistently elevated BP or normotension with the use of antihypertension medication after KT
The definition of HTN in Kidney Transplant recipients remains controversial and hard outcomes related to BP levels are still limited. Cardiology American guidelines recommended a target BP< 130/80mmHs in post-Renal transplant recipients until there is stronger evidence of an association between BP level and outcome in Kidney Transplant recipients. Pathogenesis of Post Transplant Hypertension
Immediate post-transplant period:-
During this time, post-Transplant HTN is generally a result of external factors like Transplant surgery, I.V fluid, and high dose of steroid Peri-Transplant hypervolemia:
I.V fluid during surgery given and post-operative period can lead to hypervolemia and particularly in pts with delayed graft function. The same study showed that hyper volume was associated with elevated systolic, diastolic, and mean artial pressure.
High dose steroid
High-dose IV steroids are the cause of HTN immediately post-Transplant period. And the mechanism is unclear and usually dose of more than 20 mg of prednisolone per day is the threshold for having HTN. Rebound HTN:-
Discontinuation of anti-hypertensive therapy can lead to rebound hypertension-most probably due to sudden discontinuation of beta blocker , clonidine, and beta-adrenergic against- and this is due to sympathetic overactivity. Inappropriate pain management:-
Acute pain associated with elevated BP via sympathetic ravens system activation, leading to an increase in peripheral vascular resistance, heart rate, and stroke volume
Early post-Transplant period
Early post-transplant period is the time between 24 and 52 weeks post-transplants Weight gain
Between 6-12 months post-transplant BMI >= 30kg/m2 after transplant is associated with post Transplant HTN. Calcineurin inhibitors
The prevalence of HTN in Kidney Transplant recipients is between 70 and 90% two mechanisms of CNI-induced post-transplant HTN:-
1- Interfering vascular tone-
2- Renal sodium Transplant handling steroids
-a systemic review and meta-analysis revealed that steroid avoidance or withdrawal decreases CVS outcomes including HTN but increases the risk of acute rejection.
A randomized control trial demonstrates no difference in blood pressure change between alternative day and daily prednisone. Hypertensive donor Kidney
Several animal studies revealed a renal rate in the development of HTN Kidney transplantation From Idiopathic hypertension rate donors to genetically normotensive recipients led to post Transplant HTN resulting from deceased renal salt excretion Transplant Renal Artery Stenosis
TRAS is a common vascular complication that leads to worse renal allograft function and CVS complications.
Including post-transplant HTN 1-5% of post transplant, HTN is secondary to TRAS.
The cause is immunological and nonimmunological causes.
Symptoms and signs of TRAS are non-specific but can be present by unexplained worsening of renal allograft function or uncontrolled HTN.
CDU is the initial imaging study used because it is non-invasive
Peak systolic velocity of main Renal Artery and postenotic intrarenal arterial resistive index. Are used to determine and grade the severity of TRAS.To confirm the diagnosis using CT and MRA Renal Artery.
Therapeutic options for TRAS are pharmacological therapy in addition to renal artery angioplasty with stenting or surgical revascularization.
Use ARB or ACE or diuretics to control the BP.
Angioplasty with stenting if:-
1- Worsening serum creatinine.
2- Uncontrolled HTN due to TRAS. Late post-Transplant period
Factors that can result in a late post-Transplant period:-
1- Chronic renal allograft dysfunction:–acute and chronic renal allograft injuries both are associated with HTN.
HTN and immunological factors affect the expression of growth factors in Renal allograft and may be the cause of chronic renal allograft dysfunction fibroblast growth factor is
FGF is an independent risk factor of renal allograft loss, CVS, and all causes of mortality in Kidney transplant recipients
High level of FGF is associated with increased SBP and DBP as well as an incident HTN in nonhypertensive yang adults> Obstructive sleep Apnea:
In one of the studies kidney transplant patients with OSA required a significantly higher number of anti-hypertensive medications and tend to have higher SBP.
OSA is associated with CVS risks, morbidity, and mortality. The outcome of HTN after kidney transplantation
Pre-transplant BP is associated with renal allograft and patient survival outcomes after kidney transplantation. post renal transplant HTN is associated with poorer renal allograft and patient outcomes .no sufficient data about CVS and mortality outcomes related to isolated diastolic HTN in a kidney transplant recipient and more studies are required to determine appropriate management target for isolated diastolic HTN in this population. CVS outcomes related to post-transplant HTN:
Kidney transplant recipients with left ventricular hypertrophy or HF PEF have increased mortality and morbidity and also they are at high risk for cardiac-related events Blood pressure management
Non-pharmacological such as diet, exercise, and stress reduction are crucial in the management. Pharmacological management Use of Antihypertensive medication:
Diuretics:
Usually given in the peri-transplant period.
Loop diuretics are usually indicated during the immediate and early post-transplant period.
Thiazides
Uncommon used in kidney transplantation recipients because of their side effects. Mineralocorticoid Receptor antagonist
Use post-KTRs but can cause hyperkalaemia. some evidence for antiproteinuric effect and safety in transplant recipients even when combined with ACE I or ARBs. Beta Blocker
Has a cardioprotective effect and survival benefits and also decreases proinflammatory cytokines which increase the risk of atherosclerosis. Calcium channel blocker
Is an appropriate agent for post-transplant HTN and also can prevent post-transplant acute tubular injury or DGF. Angiotensin-converting Enzyme inhibitors and angiotensin 2 Receptor Blocker
There was insufficient data regarding the benefit of ACEi or ARBs therapy for the patient or renal allograft survival. Alpha -Antagonists
Are rarely used as the initial or as a single antihypertensive agent in kidney transplant recipients. Alpha2-Agonist
Centrally acting alpha-agonist e.g methyldopa, clonidine.
In summary, there is no drug of choice for Bp control after kidney transplantation. Several factors to select the appropriate antihypertensive medication.
The most commonly used medication is calcium channel blocker is the most frequently used combination in post-kidney transplantation. Other management for blood pressure native nephrectomy
There is evidence that kidney recipient with pre or post transplant native recipient has decreased blood pressure when compared to those without native nephrectomy. Native renal sympathetic denervation
The effect of RDN on BP control was established, there are surgical or catheter ablation denervation, bilateral native nephrectomy in kidney transplantation is invasive and carries risk so it should be reserved for selected patients Conclusions
HTN is a very common disease in CKD and ESRD and remains after kidney transplantation.24 hours ABPM is the gold standard measurement. The choice of antihypertensive medication requires the clinician to take a transplant and immunological factor
Consideration, there is no BP target and the therapy target needs to be individualized.
In our centre, we use a calcium channel blocker .and combined it with ACE I or ARBs but we avoid in early transplant period
Abdullah Raoof
2 years ago
Approach and Management of Hypertension After Kidney Transplantation EPIDEMIOLOGY OF POST-TRANSPLANTHYPERTENSION:
Over all prevalence of HT is increasing gradually. May be due to introduction of CNI the prevalence range from 24-90%. DEFINITION OF POST-TRANSPLANT HYPERTENSION:
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation. Different studies mention different definition of HT, 140/90 or 145/95 or 150/90.
HT post kidney transplantation can categorized into four groups:
1- persistent HTN.
2- recovered HTN.
3- persistent normotension.
4- post-transplant HTN
isolated systolic HTN defined as SBP <140 and DBP <90 mmHg. It is common in elderly patient. diastolic HTN is defined as DBP of < 90 mmHg with a SBP <140 mmHg, is more common in younger,
sedentary individuals.
A recent 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a target BP of <130/80 mmHg. PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION:
Immediate Post-transplant Period:
a- Peri-transplant Hypervolemia
b- High-Dose Steroids
c- Rebound Hypertension Early Post-transplant Period:
a- Weight Gain
b- Calcineurin Inhibitors
c- Altered vascular tone
d- Increased renal sodium transport handling
e- Steroids
f- Transplant Renal Artery Stenosis (TRAS) Late Post-transplant Period:
Chronic Renal Allograft Dysfunction
Fibroblast Growth Factor (FGF) 23
Obstructive Sleep Apnea
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
During the post-transplant period, elevated BP is associated
with poorer renal allograft and patient outcomes.
Opelz et al. conducted a retrospective study conclude that
Increased post-transplant SBP and DBP were associated with progressively decreased renal allograft function and death-censored chronic graft failure. Cardiovascular Outcomes-Related to Post-transplant Hypertension:
HTN is one of the most important risk factors for heart
failure, particularly heart failure with preserved ejection fraction (HFpEF). BLOOD PRESSURE MEASUREMENT:
can be standardized with the following definitions:
– the meanof three non-invasive BP measurements is referred to as office blood pressure (OBP);
– recording at least twice the daily average of two home blood pressure readings over aminimum of 4 days is referred to as home blood pressure monitoring (HBPM),
– 24-h ambulatory blood pressure monitoring (24-h ABPM), which requires wearing an electronic blood pressure measurement device to record and averages multiple readings over a 24 h period .
A 24-h ABPM provides the average of both day and night
BP readings. Physiological decreases in nocturnal BP further
classifies patients into dippers, non-dippers, and reverse dippers.
Lee et al. demonstrated a significant decrease in the nocturnal reduction in SBPafter kidney transplantation.
A 24-h ABPM can address and assist with the common
misclassification of HTN diagnosed traditionally by OBP or
HBPM. Compared with OBP, a 24-h ABPM led to 61% disagreement in diagnosis. BLOOD PRESSURE MANAGEMENT:
there is no drug of choice for BP control after kidney transplantation. Several factors are involved in selecting the appropriate antihypertensive medications include immunologic and non-immunologic factors as well as the time
after kidney transplantation. Diuretics:
Diuretics are not commonly used as the first line antihypertensivemedication in kidney transplant recipients Loop Diuretics:
Volume control rather than BP control is the indication
for loop diuretics in kidney transplant recipients, especially
during immediate and early post-transplant periods Thiazides:
Thiazide diuretics are commonly used antihypertensives
in general population. They are however uncommon in
the management of kidney transplant recipients because of
their metabolic side effects which include hyperglycemia,
hyperuricemia, hypercalcemia, and hyponatremia
Mineralocorticoid Receptor Antagonists:
Mineralocorticoid receptor antagonists (MCRA) have CV
benefits and antiproteinuric effect but are not
commonly used antihypertensives in kidney transplant
recipients, especially those with impaired renal allograftfunction. Hyperkalemia is a common side effects of MCRA and it may be worse in kidney transplant recipients who have CNI-induced hyperkalemia. Beta-Blockers:
The cardioprotective effects and survival benefit of beta-blockers make them a favored medication in the general and
ESRD populations . In kidney transplant recipients, a
recent retrospective study from 2001 to 2014 showed that beta blockers are the most common used antihypertensive medication. Calcium Channel Blockers:
Calcium channel blockers inhibit entry of calcium into vascular
smooth muscle cells, resulting in vascular vasodilation.
Since the vasoconstrictive effect of CNIs leads to post-transplant HTN (172), calcium channel blockers are thought to be an appropriate agent for post-transplant HTN. Theoretically their vasodilatory effect can counteract the vasoconstrictive effect of CNIs and improve BP control. Angiotensin-Converting Enzyme Inhibitors:
Since proteinuria is a surrogate marker for renal disease, lowering proteinuria is one strategy to slow the progression of CKD. ACEIs and ARBs are antihypertensive agents with known
antiproteinuric effect. ACEIs inhibit angiotensin-converting
enzyme, which converts renin to angiotensin. There was insufficient data regarding the benefits of ACEI or ARB
therapy in terms of patient or renal allograft survival
(ACEI) and Angiotensin II Receptor Blockers (ARB) Alpha1-Antagonists:
Alpha1-antagonists are rarely used as the initial or as a single
antihypertensive agent in kidney transplant recipients. OTHER MANAGEMENT FOR BLOOD PRESSURE:
1- Native Nephrectomy.
2- Native Renal Sympathetic Denervation.
3- Surgical Renal Denervation by Bilateral Native Nephrectomy.
4- Catheter Ablative Renal Denervation.
Q2How do you manage hypertension after kidney transplantation in your workplace?
First of all to search for any treatable cause for example volume overload, then to apply the general measure as for any hypertensive patient . than to use medication most commonly used medication involves calcium channel blocker .
CARLOS TADEU LEONIDIO
2 years ago
Briefly summarise this article
The definition of hypertension in kidney transplant recipients is a very controversial topic, but in this work the following was used: as persistently high blood pressure (BP) levels or normotension with the use of antihypertensive drugs after successful kidney transplantation. The importance of hypertension is due to the fact that it is the most common risk factor for cardiovascular diseases, which are the main cause of morbidity and mortality among kidney transplant recipients.
IMPORTANCE OF PRESSURE LEVELS:
Pre-transplant BP is associated with renal allograft and patient survival outcomes after kidney transplantation. Very low pre-transplant SBP (< 110 mmHg) and DBP ( < 500mmHg) are associated with a decrease in renal allograft loss. Specifically during dialysis lower pre- and post-dialysis DBP are associated with better patient survival post-transplantation.
During the post-transplant period, elevated BP is associated with poorer renal allograft and patient outcomes. However, as discussed above, various forms of renal allograft injury are also associated with post-transplant HTN.
CATEGORIZATION:
In general, there are pre- and post-transplant etiologies for the development of post-transplant hypertension, and defining when it first occurred helps to define the differential diagnoses for the etiology of post-transplant hypertension, leading to personalized therapy. The most used categorization divides post-transplant hypertension into: immediate X early X late
Immediate post-transplantation: – hypervolemia: used in the pre- and perioperative period – Corticosteroids: effect of immunosuppressive pulse therapy – Rebound hypertension: due to discontinuation of antihypertensive drugs in the preoperative period; – acute pain Early post-transplant – Weight gain – Calcineurin inhibitors: altered vascular tone and/or management of sodium transport – Corticosteroids – donor kidney with hypertension – sodium retention – Renal artery stenosis: surgical anastomosis, native vascular disease, fibromuscular dysplasia, vascular rejection Late post-transplant – Graft dysfunction – Fibroblast growth factor – obstructive sleep apnea
HYPERTENSION MANAGEMENT:
– Non-pharmacological: pain treatment, exercises, diet and stress reduction. – Pharmacological: – Diuretics: loop (preferred for volume control) X Thiazides – Mineralocorticoid receptor antagonists: they are not often used because they induce hyperkalemia, but they have excellent effects for cardiovascular protection and proteinuria decrease B beta-blockers: they are the most commonly used, they decrease inflammatory cytokines – ACE inhibitors and ARBs – decreased proteinuria, but no evidence of improved patient or renal allograft survival – Calcium channel blockers: vasodilator effect that opposes the vasoconstrictor of CNIs. They also prevent acute renal tubular injury. – Alpha 1 inhibitors – are rarely used, there is no evidence that alpha 1 antagonists provide a superior antihypertensive effect or delay the progression of renal allograft dysfunction -Alpha 2 inhibitors – central action, inhibiting sympathetic activity.
In summary, there is no drug of choice for controlling BP after kidney transplantation, and the best treatment is the one planned for each patient.
How do you manage hypertension after kidney transplantation in your workplace?
In obvious cases of immediate post-transplant hypertension, we try to induce a decrease in volemide with diuretics and, if that fails, institute hemodialysis. In other situations, we tried to manage drugs, such as decreasing the dose of corticoids and CNI, and introducing antihypertensive drugs.
Hamdy Hegazy
2 years ago
Briefly summarise this article
Post-TX hypertension is classified into: 1- Persistent: Pre-TX HTN that continues Post-TX. 2- Recovered: Pre-TX HTN that disappears Post-TX. 3- Post TX HTN: denovo HTN post-TX. In RTX: target BP less than 130/90. Causes of Post-TX HTN: 1- Hypervolemia. 2- High dose of steroids used in induction immunosuppression. 3- Rebound HTN: from reducing or stopping anti-HTN medications. 4- Pain induced. 5- Weight gain. 6- CNI induced. 7- Steroid induced. 8- Transplant renal artery stenosis. 9- Chronic allograft nephropathy. 10- OSA. 11- FGF-23. Management of Post-TX HTN: a- Non-pharmacological. b- Pharmacological: 1- Diuretics especially loop diuretics if fluid overloaded. 2- B-blockers. 3- CCBs: especially in CNI induced HTN. 4- ACE.I/ARBs: postponed to 3 months post TX, useful if DM, HF, proteinuric. 5- Alpha blockers. 6- Alpha-2 agnoists. 7- Native nephrectomy. 8- Native Renal sympathetic denervation. 9- Catheter ablative renal denervation.
How do you manage hypertension after kidney transplantation in your workplace?
Non pharmacological, CCBs, diuretics commonly used in my work place in the early post TX period.
Ahmed Abd El Razek
2 years ago
INTRODUCTION
Renal transplantation is the best treatment for advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) of greater survival benefit and achievement of better quality of life. However, still cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in renal transplant recipients affecting their survival. The most common risk factor for CVD is hypertension.
EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION
The incidence of post-transplant hypertension is estimated about 24% ranging to 90% owing to the wide use of cyclosporine (CsA) necessitating the increased number of antihypertensive agents administered to achieve the ultimate control of blood pressure.
DEFINITION OF POST-TRANSPLANT HYPERTENSION
A persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation is the best definition for post-transplant hypertension. In other words, Post-transplant HTN is de novo HTN after kidney transplantation.
Two main points were needed to establish regarding the normal blood pressure value post transplantation and whether hypertension existed pretransplantation or not.
American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a target BP of <130/80 mmHg.
Immediate Post-transplant Period
It is mostly due to some external factors as transplant surgery, IV fluids, and high doses of steroids.
Whereas hypervolemia is evident particularly in patients with delayed graft function (DGF). Weight gain exceeding the pre-transplant dry weight was correlated to immediate post-transplant HTN. BP, heart rate, urine output, central venous pressure, and pulmonary artery pressure are important surrogates to assess the volume status besides the body weight.
High-Dose Steroids may lead to alterations in intrinsic pressor response manifesting arterial vascular resistance.
Rebound Hypertension
Beta-adrenergic agonists, clonidine and beta-blockers are commonly linked to this phenomenon. Sympathetic over activity without renin angiotensin system mediation is the main culprit in the mechanism of rebound HTN from clonidine.
In patients with underlying coronary artery disease (CAD) rebound HTN from beta-blockers causes elevated BP and heart rate, up to serious cardiac events including angina, myocardial infarction, or sudden cardiac death.
Inappropriate Pain Management
Acute pain is causes markedly elevated BP by sympathetic nervous system activation with subsequent increases in peripheral vascular resistance, heart rate, and stroke volume. Also stimulation of the neuroendocrine system via hypothalamic-pituitary adrenal axis aggravates pain-induced HTN.
Early Post-transplant Period
The most contributing factors are:
Weight Gain:
Weight gain is common between 6- and 12-months post-transplantation. Obesity (BMI more than 30 kg/m2) after renal transplantation is significantly causes post-transplant HTN.
Calcineurin Inhibitors
The prevalence of HTN in renal transplant recipients ranges between 70 and 90% compared to pre-CNI era which was estimated by 40 to 50%.
Two main mechanisms lead to CNI-induced post-transplant HTN via interfering vascular tone and renal sodium transport handling. Altered vascular tone in the form of both increased vasoconstriction and impaired vasodilation while CsA results in sympathetic system stimulation with the association of subsequent sodium retention by the effect of phospho-protein synapsin which is found on microvesicles within renal sensory nerve endings. Thiazide diuretics are known to be effective for CNI-induced HTN being of salt sensitive aetiology.
Steroids
The prevalence of HTN decreased in patients taking alternate day steroid therapy. Also despite conflicting data regarding graft survival, steroid withdrawal or avoidance regimens are being adopted recently specifically for those who would be at greater risk for CV outcomes but have immunologically lower risk of rejection.
Hypertensive Donor Kidney
A study conducted in renal transplant recipients who did native nephrectomy prior to renal transplantation from normotensive donors concluded that all recipients became normotensive post-transplant without any need for antihypertensive medications. However, another study in recipients with known familial HTN, renal transplantation from any type of kidney did not affect the prevalence of post-transplant HTN. So there is a proposed role for kidney and genetic kidney disease in developing HTN.
Transplant Renal Artery Stenosis (TRAS)
TRAS may occur at any time post renal transplantation, commonly diagnosed between 3 and 24 months post transplantation. The prevalence of TRAS increased from 2.4 to 12.4% after the introduction of color Doppler ultrasonography (CDU) in 1985, due to improved detection with noninvasive testing.
The pathogenesis of TRAS is complex varying between both non-immunological and immunological contributing factors. The non-immunological factors preclude vascular damage at the time of surgical anastomosis between the donor renal artery and recipient artery as well as the existence of native vascular diseases in both donor and recipient arteries. Also the connection between these smaller arteries might be predisposed to narrowing followed by subsequent development of TRAS. The association between post anastomotic TRAS and de novo class II donor-specific antibodies raises the possibility of immunologic contribution to atherosclerotic TRAS.
The most important common clinical clue that directs to a work-up for TRAS is either unexplained worsening of renal allograft function or uncontrolled HTN. Using imaging studies is preferred notably the CDU being non-invasive, widely available, and relatively inexpensive by assessing the RI to determine and grade the severity of TRAS.
Therapeutic options include pharmacological management alone or adding renal artery angioplasty with stenting or surgical revascularization upon need.
Late Post-transplant Period
The main causes proposed are Chronic Renal Allograft Dysfunction, Fibroblast Growth Factor (FGF) 23, and Obstructive Sleep Apnea. OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
In the post-transplant period, elevated BP is associated with poorer both renal allograft and patient outcomes. Increased post-transplant SBP and DBP were associated with progressively decreased renal allograft function and death-censored chronic graft failure according to Opelz study. Cardiovascular Outcomes-Related to Post-transplant Hypertension are manifested by heart failure with preserved EF.
BLOOD PRESSURE MANAGEMENT
Non-pharmacologic means like healthy diet, exercise, and stress reduction are essential in the management prior to pharmacological treatment. Thiazides can be used in CNI post-transplant HTN being salt sensitive .CCB can be used with monitoring of drug levels. Other lines as diuretics, ACEI or ARBS are discouraged. So antihypertensive agents should be tailored to each patient.
Management of HTN post renal transplantation in our centre is carried out by meticulous identification of the cause, lifestyle modification in the form of healthy diet ,exercise ,cessation of smoking ,perfect fluid balance guided by the patient’s volume status, early detection of rejection, and minimizing steroid doses the sooner the better especially for those with lowest immunological risk. The usage of antihypertensive agents is tailored to every patient individually.
Last edited 2 years ago by Ahmed Abd El Razek
Wadia Elhardallo
2 years ago
Briefly summarise this article
Introduction:
· Cardiovascular diseases are the leading cause of mortality in post-transplant patients, and Hypertension is one of the most common cardiovascular co-morbidities (prevalence ranged from 24 to 90%) it’s important to diagnosed and properly managed.
· Its define as a persistently elevated BP or normotension with use of antihypertensive medications *as SBP ≥140 and DBP <90 mmHg in most of the society guidelines . and divided to 4 types depending on BP status pre transplant: persistent HTN, recovered HTN, persistent normotension, and post-transplant HTN.
Depending on timing to transplantation factors contributed to raise in blood pressure vary:
Immediate Post-Transplant Period:
ü Peri-transplant hypervolemia
ü Induction immunosuppressive medications
ü Rebound hypertension
ü Inadequate pain control
Early Post-Transplant Period: define as between 24 and 52 weeks’ post-transplantation:
ü Surgical related: Intraoperative volume administration, Transplant renal artery stenosis
ü related to the Donor: Hypertensive kidney, Family history of HTN in donor, Transplant renal artery stenosis
ü related to the Recipient: Pre-existing HTN, Renal allograft dysfunction, Dietary sodium intake, Metabolic syndrome, TRAS, OSA, Failed native kidneys, Sympathetic over activity
Blood Pressure Management: target ≤130/80
Non-pharmacologic:
ü Dietary control
ü Life style modification: exercise, and stress reduction
Pharmacological: antihypertensive medications:
Diuretics : not the first line Loop ,Thiazide:
· Used for volume control
· May use with ACEI or ARB in TRAS
· Renal sodium excretion defect in CsA-induced HTN
CCB calcium channel blocker
· Afferent arteriolar vasodilatation
· May improve renal allograft function and lower DGF but inconclusive
*Non-dipyridamole CCB is CYP450 inhibitor and increases CNI level
ACEI/ARB
· Anti-proteinuric
· Cardioprotection
· May use with diuretic in TRAS
Beta-blockers: cardioprotection
Mineralocorticoid receptor antagonists:
– Systolic dysfunction – Safe with using ACEI and ARB but increase hyperkalaemia
Alpha1 antagonist :Generally, not the first line
Alpha2 agonist
· Lower plasma renin activity that modulated renal vascular resistance and lower MAP.
· No change in GFR and effective renal plasma flow.
Other Interventions: for resistant HTN: Specific to certain etiologies, such as Transplant Renal Artery Angioplasty ± Stenting Bilateral Native Nephrectomy
Renal sympathetic denervation
How do you manage hypertension after kidney transplantation in your workplace?
During perioperative time: close monitor to BP, with adequate pain control to avoid low or high reading. if needed parenteral antihypertensive medication can be used (labetalol example)
At hospital discharge advice about weight control, salt low, and general dietary plan with nutritionist
Follow up visit and BP regular measuring to diagnose any HTN early.
When BP reading is high: looking for drug level, assessment of graft function, volume status and all other possible factors
Medication: CCB is commonly used as first line, we avoid ACEi specially at early post-transplant period so not to be confused if creatinine readings start to rise.
Nandita Sugumar
2 years ago
Summary
This article is about hypertension following kidney transplant. The treatment options for resistant hypertension post transplant as well as antihypertensive medications and their mechanism of action has also been discussed.
The risk factors that make a recipient more susceptible than others to hypertension following kidney transplant include the presence of 3 factors listed below :
obesity
diabetes mellitus
hyperlipidemia
Hypertension post transplant can occur in different periods :
immediate
early
late post transplant period
In the immediate period, volume overload contributes to development of hypertension. Hypertension can develop in any period associated with donor kidneys or immunosuppressive medications.
Factors contributing to development of post transplant hypertension according to different time periods mentioned above :
Immediate post transplant period
Peri transplant hypervolemia
induction immunosuppression
rebound hypertension
inadequate pain control
Early post transplant period
weight gain
calcineurin inhibitors
steroids
hypertensive donor kidney
transplant renal artery stenosis
Late post transplant period
chronic renal allograft dysfunction
fibroblast growth factor 23
obstructive sleep apnea
failed native kidneys
sympathetic overactivity
Two common causes of resistant but treatable hypertension following transplant include :
Transplant renal artery stenosis – TRAS
Obstructive sleep apnea – OSA
An important factor contributing to hypertension in the late post transplant period includes chronic renal allograft dysfunction.
Increase in fibroblast growth factor 23 or FGF23 is associated with increased cardiovascular and all cause mortality in kidney recipients.
One of the major issues adding to the burden of hypertension is improper pain management. NSAIDs are to be avoided in the post transplant phase and opioids are acceptable. NSAIDs can cause negative renal effects such as reduced renal plasma flow.
24 hour measurement of BP is essential but it is inconvenient and not utilized in many centers.
Bilateral native kidney nephrectomy can be a treatment option for resistant post transplant hypertension. Evidence suggests that recipients who have undergone native nephrectomy pre or post transplant have decreased BP compared to those without native nephrectomy. Native renal denervation can also be used.
Antihypertensive medications that can be used include diuretics, calcium channel blockers, beta blockers, RAAS blockers such as ACEi, ARBs, mineralocorticoid receptor antagonists.
Further research is needed to develop stronger evidence concerning the pathogenesis of post transplant hypertension, appropriate measurement of BP, effective pain management, appropriate dosing and application of antihypertensive medications and the surgical methods of treatment for resistant post transplant hypertension.
saja Mohammed
2 years ago
Introduction
Hypertension Post-transplantation very common and complex pathology, many immunological and nonimmunological factors related to transplantation can lead to hypertension in addition to medication effects, in particular, CNI, transplant renal artery stenosis (TRAS), OSA, metabolic syndrome, dyslipidemia, obesity, and DM, it carries high cardiovascular risk and impacts the graft survival, post-transplant hypertension can be classified as early, immediate and late after TX, which usually associated with chronic graft dysfunction .this article review the causes, pathogenesis of hypertension post-transplantation, classification and treatment options including pharmacological and interventional angioplasty or renal denervation and native kidney nephrectomy in the resistant type of hypertension based on the available evidence from the guideline.
Definition of post-kidney transplantation
The definition and prevalence Of HTN post-transplantation are quite variable between studies due to variation in the definition and it’s in the range between 25-90%, however, target Bp should be < 130/80
1. Persistent high blood pressure
2. recovered HTN,
3. persistent normotension,
4. post-TX HTN, and with aging isolated systolic HTN is also common, Post-transplant HTN is associated with increased CVD morbidity.
Post-transplant HTN
Immediate post-transplant period due to IVF peri-and postoperative time which leads to volume overload
Induction immunosuppression medications like steroids with increased sympathetic overactivity
Rebound HTN especially those on BB,
post-operative pain management also due to sympathetic overactivity.
Early post-transplantation
Between 24-52 weeks post-TX, involve many factors
Weight gain
immunosuppression therapy (CNI, Steroids’ )
Hypertensive kidney donor
Transplant RAS
CNI Induced HTN
Change of Vascular tone, with arteriolar vasoconstriction due to the effect of endothelin, not angiotensin 11, and reduced vasodilator like nitic oxides
CNI induces salt-sensitive HTN via activation of the WNK- SPAK-NCC pathway similarly to a rare genetic form of HTN, called familial hyperkalemic hypertension (FHHt, also called Gordon syndrome or pseudohypo-aldosteronism type 2), so patient will have normal anion gap hyperkalemic acidosis with low fractional excretion of chloride with hypercalciuria and thiazide diuretics will be effective for CNI induced hypertension
Late post-transplantation
Chronic allograft dysfunction
Fibroblast growth factor (GF23) is considered an independent risk factor for graft loss
OSA post-transplantation more in males with higher BMI, DM, impaired graft function, on hypnotic medications and it’s associated with higher CVD, PVD, and CVA risk
Failed native kidneys
Sympathetic overactivity
RAS, renal artery stenosis
So in summary post-transplantation hypertension is quite common and variable prevalence between 70-90% in the era of CNI and can be classified as an immunological risk for HTN including DGF acute or chronic rejection immunosuppression ( CNI ,steroids )
the non-immunological risk factors include
donor-related factors ( HTN kidney donor or FH of hypertension in the donor, ARAS,
recipient-related factors (preexisting HTN, ARAS, medications
surgical factors ( volume load , RAS)
MICHAEL Farag
2 years ago
post-transplant hypertension is complex and is a result of the interplay between immunological and non-immunological factors. Post-transplant hypertension can be divided into immediate, early, and late post-transplant periods. a BP of <130/80 mmHg is a reasonable target. kidney transplant recipients can be divided into four groups: persistent HTN, recovered HTN, persistent normotension, and post-transplant HTN. Common causes of post-transplant hypertension according the period of transplant a) immediate post-transplant 1- hypervolemia 2- induction Is medications 3- rebound hypertension 4- inadequate pain control b) early post-transplant 1- weight gain 2- CNI and /or steroids medications 3- hypertensive transplant donor 4- TRAS c) late post-transplant 1- Chronic allograft dysfunction 2- failed native kidneys 3- fibroblast growth factor 23 4- OSA 5- sympathetic overactivity OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION Elevated BP is associated with poorer renal allograft and patient outcomes BLOOD PRESSURE MANAGEMENT Non-pharmacologic interventions, such as diet, exercise, and stress reduction, should always be part of treatment of HTN. Anti-hypertensive medications tailored according to patient condition and co-morbid Procedural or surgical interventions; Specific treatment modalities • Transplant renal artery angioplasty ± stenting • Continuous positive airway pressure (CPAP) • Bilateral native nephrectomy • Native renal denervation
How do you manage hypertension after kidney transplantation in your workplace?
– In each opd visit
– -if patient high risk to have high bp and can’t detect it in the opd , so need ambulatory monitoring
– I don’t consider high bp unless confirmed by 3 readings in different occasions with physical and mental rest, or through 24-hour monitoring
– Educate the patient about the non-pharmacological measures
– If patient needs starting antihypertensive medications so should consider other comorbids, eGFR, proteinuria
– If resistant so need more investigations to detect the cause
Giulio Podda
2 years ago
After successful kidney transplantation, hypertension is one of the most common cardiovascular co-morbidities. People with metabolic diseases (diabetes, obesity etc) are more commonly affected. Prevalence of post-transplant HTN ranges from 24 to 90%.
Both immunological and non-immunological factors play a key role in the pathogenesis of post-transplant hypertension.
Post-transplant hypertension classification is divided into immediate, early, and late post-transplant periods and this classification is used to help clinicians to choose the appropriate treatment and to determine the etiology.
In the Immediate post-transplant period patient may present hypertension secondary to: -Volume overload following intravenous fluid administration (peri-transplant
hypervolemia particularly in patients with delayed graft function)
-Steroids (result from alterations in intrinsic pressor response leading to arterial vascular
resistance)
-Rebound hypertension (result of sympathetic Overactivity following a sudden
discontinuation of antihypertensive therapy)
-Inappropriate pain management (via sympathetic nervous system activation, leading to
increases in peripheral vascular resistance, heart rate, and stroke volume).
In the early post operative period it was found that systolic HTN (140 mmHg) occurred at the mean duration of 26–50 weeks after kidney transplantation.
The most common factors that contribute to hypertension during this period include:
-Weight gain
-Steroids
-Calcineurin Inhibitors (increased vasoconstriction and impaired vasodilation contribute
to CNI-induced post-transplant HTN, Renal vasoconstriction and sympathetic excitation
with subsequent sodium retention)
-Hypertensive Donor Kidney (Salt intake can lead to water retention and HTN, especially
in salt sensitive individuals)
-Transplant Renal artery Stenosis (1–5%of post-transplant HTN is secondary to TRAS
and is generally diagnosed between 3 and 24 months post transplantation).
In the Late Post-transplant Period, causes of Hypertension include:
-Chronic Renal Allograft Dysfunction and OSA. With Chronic renal allograft dysfunction as part of chronic kidney disease affecting the graft there is an increase FGF23 which is associated with increased cardiovascular and all-cause mortality in kidney transplant recipients. However, remains unclear the relation between post-transplant hypertension and increased FGF23.
Very low pre-transplant SBP (<110 mmHg) and DBP (<50 mmHg) are associated with a
decrease in renal allograft loss. During the post-transplant period, elevated BP is
associated with poorer renal allograft and patient outcomes. Kidney transplant
recipients with left ventricular hypertrophy (LVH) or HFpEF have increased morbidity
and mortality and are at high risk for cardiac-related events.
BP can be standardized with office blood pressure (OBP) which is the mean of three non-invasive BP measurement, the home blood pressure monitoring (HBPM) recording at least twice the daily average of two home blood pressure readings over a minimum of 4 days and the 24- h ambulatory blood pressure monitoring (24-h ABPM) (record and averages multiple readings over a 24 h period). Management of hypertension in renal transplant patient involve pharmacological and non-pharmacological approach. A reasonable target BP in renal transplant patient is < 130/80 mmHg. Non pharmacological approach include physical activity, low salt diet and stress reduction. Pharmacological approach include antihypertensive medications: -Diuretics: Not commonly used as the first line antihypertensive medication in kidney
transplant recipients. Loop Diuretics are used for Volume control rather than BP control
is the indication in kidney transplant recipients, especially during immediate and early
post- transplant periods. Thiazides may theoretically control CNI-induced HTN since CNI-induced HTN is salt sensitive
-Mineralocorticoid Receptor Antagonists (MCRA): notcommonly used in kidney transplant recipients, especially in case of declining graft function. Common side effects of MCRA is hyperkalemia. -Beta Blockers: cardioprotective effects and survival benefit both in the general and ESRD populations. BBs are the most common used antihypertensive medication in
kidney transplant recipient. Kidney transplant recipients on BB seems to have a
significant survival advantage compared to those not on BB. Protective mechanism of
beta-blocker is through inhibition of the sympathetic nervous system. BB mask
symptoms of hypoglycemia and thyrotoxicosis and may worsen lipid profiles.
Possible side effect include Hyperkalemia
-Calcium Channel Blockers (CCB): its vasodilatory effect can counteract the
vasoconstrictive effect of CNIs and improve BP control. Prevent post-transplant acute
tubular injury (ATI) or DGF. Diltiazem has lower incidence of ATI, higher GFR with
primary function, lower incidences of rejection at 1 month post-transplant. Diltiazem
increases CsA level. Recent systematic review and meta-analysis of 60 trials including
3,802 patients showed that, compared to placebo or no treatment, CCB decreased graft
loss [risk ratio (RR) of 0.75, 95% confidence intervals (CI) 0.57–0.99] and increased
GFR [mean difference (MD) 4.5 mL/min, 95% CI 2.2–6.7]. CCB can cause peripheral
edema and muscle weakness (particularly when used in combination with steroids)
and gum hyperplasia (especially when calcium channel blockers are used with CsA)
-Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor Blockers
(ARB): Data regarding the benefits of ACEI or ARB therapy in terms of patient or renal
allograft survival are insufficient. RAAS activation is associated with interstitial fibrosis
and tubular atrophy (IF/TA) (IF/TA are one of the most common causes of renal allograft
loss). Perindopril seems to prevent cortical interstitial expansion (marker of fibrosis in
CKD patients with diabetic nephropathy). Despite their antiproteinuric effect during the
immediate and the early post-transplant period, they are generally not used as they
decrease GFR. –Alpha 1 Antagonist: They reduce BPby decreasing peripheral vasoconstriction. They
are not commonly used as initial or as a single antihypertensive agent in kidney
transplant recipients.
-Alpha2 Agonists: Centrally acting alpha2 agonists work on presynaptic alpha2
adrenoceptors in the central nervous system. They suppress the central sympathetic
activity. methyldopa and clonidine are the most commonly used alpha2 agonist. methyldopa, as a monotheraphy is associated with antihypertensive tolerance, edema, and weight gain. Clonidine is also associated with weight gain and progressive resistance with continued use. Other Non pharmacological interventions for BP control include:
-Bilateral native nephrectomy: In kidney transplantation, the presence of failed native
kidneys is associated with post-transplant resistant HTN. ACEIs and native
nephrectomy may need to be considered
-Native renal denervation: In failed native kidney there is a sympathetic overactivity
which may lead resistant HTN.
-Surgical Renal Denervation by Bilateral Native Nephrectomy
How do you manage hypertension after kidney transplantation in your workplace?
We encourage life style changes in the first instance. In terms of pharmacological treatment we usually start with CCB. If patient has underlying cardiac disease or AF or tachycardia we prefer BB. We consider ACEinhibitor anr ARB 3 months post transplant for patient with stable graft function and proteinuria. We monitor renal profile 7 to 10 days after commencing ACEinh/ARB to ensure the graft function remains at its baseline. If there is a drop of eGFR within 20-25 % from baseline renal function we will continue on ACE inh/ARB otherwise we reduce the dose or we stop the medication. We consider ACE inh for hypertension associated with Polycythemia
In case of volume dependent hypertension we use diuretics (thiazide). As a second line for resistant hypertension we add alfa blockers
Huda Al-Taee
2 years ago
Briefly summarise this article
Introduction:
kidney transplantation is the treatment of choice for end-stage renal disease patients. Similar to non-transplant patients, cardiovascular diseases remain the leading cause of morbidity and mortality in kidney transplant recipients. Hypertension is a usual finding in this population and one of the most common risk factors for CVD.
Epidemiology of post-transplant hypertension:
The overall prevalence of post-transplant HTN has ranged from 24 to 90%. Depending on the definition and methods of blood pressure measurement utilized, the prevalence of post-transplant HTN has been widely reported, and it has generally increased over time.
Definition of post-transplant hypertension:
It can be defined as a persistently elevated BP or normotension with antihypertensive medications after successful kidney transplantation.
The cutoff for normal BP post-transplant differs; different studies have defined post-transplant HTN with different cutoff levels for systolic and diastolic blood pressure and different requirements for the use of antihypertensive medications. in addition, the presence or absence of HTN during the pre-kidney transplant period may further categorize kidney transplant recipients into four groups: persistent HTN, recovered HTN, persistent normotension, and post-transplant HTN.
Pathogenesis of post-transplant HTN:
Immediate post-transplant period:
Peritransplant hypervolemia
induction IS
rebound HTN
inadequate pain control
Early post-transplant:
weight gain
CNI
steroids
hypertensive donor
transplant renal artery stenosis
Late post-transplant:
chronic allograft dysfunction
fibroblast growth factor 23
obstructive sleep apnea
failed native kidneys
sympathetic overactivity
Outcomes of hypertension after kidney transplantation:
Pre-transplant BP is associated with renal allograft and patient survival outcomes after kidney transplantation.
very low pre-transplant SBP (<110 mmHg) and DBP (<50 mmHg) are associated with a decrease in renal allograft loss.
during dialysis lower pre- and post-dialysis DBP are associated with better patient survival post-transplantation.
post-transplant elevated BP is associated with poorer renal allograft and patient outcomes.
There is insufficient information about CV and mortality outcomes related to isolated diastolic HTN in kidney transplant recipients.
Cardiovascular Outcomes-Related to Post-transplant Hypertension:
HTN is one of the most important risk factors for heart failure, particularly heart failure with a preserved ejection fraction
Kidney transplant recipients with left ventricular hypertrophy (LVH) or HFpEF have increased morbidity and mortality.
Uncontrolled HTN after kidney transplantation leads to structural damage to both the renal allograft and heart eventually resulting in decreased renal and cardiac functions.
BP management:
BP control during the peri-transplant period:
Diuretics: are not commonly used as the first line antihypertensive medication in kidney transplant recipients as they may cause volume depletion, electrolyte disturbances, and worsening renal allograft function. However, they are indicated and should not be avoided in certain patients in the peri-transplant period.
Loop diuretics:
Volume control rather than BP control is the indication for loop diuretics in kidney transplant recipients, especially during immediate and early post-transplant periods.
Loop diuretics can also provide prognostic value regarding renal allograft function in the immediate post-transplant period. An inadequate response, urine output <350 ml within 4 h, to a single IV furosemide dose of 1.5 mg/kg given 3 h after renal allograft anastomosis predicts increased risk of DGF.
Additional RCTs are required to determine the efficacy and safety of loop diuretic in kidney transplant recipients.
Thiazides:
Uncommon to be used in the management of kidney transplant recipients because of their metabolic side effects which include hyperglycemia, hyperuricemia, hypercalcemia, and hyponatremia.
Thiazides, however, may theoretically control CNI-induced HTN but increase serum magnesium when used with CNI.
Thiazides may be considered for kidney transplant recipients with CNI-induced salt-sensitive HTN and hypomagnesemia.
Mineralocorticoid Receptor Antagonists:
have CV benefits and antiproteinuric effects but are not commonly used antihypertensives in kidney transplant recipients, especially with reduced graft function.
Hyperkalemia is a common side effect of MCRA, and it may be worse in kidney transplant recipients who have CNI-induced hyperkalemia.
Beta-Blockers
RCTs showed CV benefits in renal transplant patients. The possible protective mechanism of beta-blocker is via mitigation of the sympathetic nervous system, which is stimulated in failed native kidneys. Also they can cause metabolic side effects, including proteinuria, hyperkalemia, and masking of hypoglycemic symptoms. Therefore, caution should be used when using beta blockers in kidney transplant recipients who are at risk to develop these side effects.
Calcium Channel Blockers
Theoretically, their vasodilatory effect can counteract the vasoconstrictive effect of CNIs and improve BP control. Also, prevent post-transplant acute tubular injury or DGF..
ACEi & ARB:
Although ACEIs and ARBs provide antiproteinuric effects, they are generally not the drugs of choice during the immediate and early post-transplant periods. This is mainly because they are known to decrease GFR.
Alpha1-Antagonists:
Are rarely used as the initial or as a single antihypertensive agent in kidney transplant recipients. there is no evidence that alpha1-antagonists provide a superior antihypertensive effect or slow the progression of renal allograft dysfunction when compared to other antihypertensive medications.
Alpha2 Agonists:
Rebound HTN is common after discontinuation of clonidine, and patients who are on clonidine prior to kidney transplant tend to have uncontrolled HTN resulting from this rebound phenomenon.
OTHER MANAGEMENT FOR BLOOD PRESSURE:
Native Nephrectomy
kidney transplant recipients with resistant HTN, ACEIs and native nephrectomy may need to be considered.
Native Renal Sympathetic Denervation:
Renal and systemic sympathetic hyperactivity contributes to the pathophysiology of resistant HTN. The effect of RDN on BP control was established.
Surgical Renal Denervation by Bilateral Native Nephrectomy:
native nephrectomy for the purpose of BP control in kidney transplant recipients should be performed in select patients with severely uncontrolled post-transplant HTN who, without treatment, would have deterioration of renal allograft function or be at increased risk of CV complications.
Catheter Ablative Renal Denervation
complete RDN by bilateral native nephrectomy in kidney transplant recipients is invasive and carries a risk of additional operation, native RDN is another option, and it should be reserved for selected patients.
How do you manage hypertension after kidney transplantation in your workplace?
By antihypertensive medications starting with calcium channel blockers as the first line, then B-blockers as the second line, if additional antihypertensives are required, we use alfa methyl dopa.
We do not use ACEi and ARB in the early post-transplant period.
Zahid Nabi
2 years ago
Hypertension is one of the most common cardiovascular co-morbidities after successful kidney transplantation.Post-transplant hypertension can be divided into
immediate,
early, and
late post-transplant periods.
Volume overload from intravenous fluid administration is common during the immediate post-transplant period and commonly contributes to hypertension seen early after transplantation.
Immunosuppressive medications
donor hypertensive kidneys are associated with post-transplant hypertension occurring at any time point after transplantation.
Transplant renal artery stenosis (TRAS) and obstructive sleep apnea (OSA) are recognized but common and treatable causes of resistant hypertension post-transplantation.
During late post-transplant period, chronic renal allograft dysfunction and associated increased fibroblast growth factor 23 (FGF23) is associated with increased cardiovascular and all-cause mortality in kidney transplant recipients.
There is no consensus that what is the optimum target BP in post transplant period however a BP of <130/80 mmHg is a reasonable target.
Different medications used for this purpose have there own advantages and disadvantages.Most commonly used drugs are
Diuretics
MRA
Beta Blockers
Calcium Channel blockers
ACEi/ARBs
Alpha 1 antagonists
Alpha2 Agonists
Calcium channel blockers are more widely used and ACEi and ARBs are mostly avoided in early transplant period.
bilateral native nephrectomyis another treatment option for resistant post-transplant hypertension. Native renal denervation offers promising outcomes for controlling resistant hypertension with no significant procedure-related complications.
Stenting for TRAS and management of OSA should always be considered
The choice of antihypertensive medication requires the transplant physician to consider immunological factors into account as well.
At our center mostly we manage it with calcium channel blockers and then do add on therapy. We don’t use ACE/ARB till six months post transplant
Mugahid Elamin
2 years ago
Hypertension is one of the most common cardiovascular comorbidities
Post kidney transplant HTN can be defined as a persistently elevated BP or normotension with the use of antihypertensive medication after successful kidney transplantation.
In this reveiw , post kidney transplation HTN refers to persistent and de novo post transplant HTN.
Causes:
Immediate post transplant period:
Peri transplant hypervolemia- Hypervolemia is significantly associated with elevated systolic, diastolic and mean arterial pressure
High dose steroids
Rebound hypertension may occur due to sudden stoppage of clonidine and beta blocker
Inappropriate pain management may causes HTN via sympathetic nervous system activation
Early post transplant period:
This means HTN in between 24 to 52 weeks of post transplantation.
causes are:
1.Weight gain.
2.Calcineurin inhibitors.
3.steroids.
4.Hypertensive donor kidney
5.Transplant renal artery stenosis
Late post transplant period:
Unless there is contraindication, kidney transplantation is the treatment of choice for advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD)
Survival benefit and quality of life are significantly improved after a successful kidney transplantation with renal allograft function.
Since the introduction of calcineurin inhibitors (CNI) in the 1980’s, short-term renal allograft survival has greatly improved
Several immunological and non-immunological causes contribute to long-term renal and patient survival outcomes.
Similar to non-transplant patients, cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality in kidney transplant recipients
Hypertension (HTN) is a usual finding in this population and one of the most common risk factors for CVD
EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION
Overall prevalence of post-transplant HTN has ranged from 24 to 90%
The prevalence of post-transplant hypertension increased could be due to introduction of cyclosporine (CsA)
DEFINITION OF POST-TRANSPLANT HYPERTENSION
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation
kidney transplant recipients are categorized into four groups:
(1) Persistent HTN occurs in patients with HTN both in the pre- and posttransplant periods
(2) recovered HTN have HTN only during the pre- but not the post-transplant period.
(3) Persistent normotensive patients have no history of HTN preceding transplant and remain normotensive post-transplant.
(4) Post-transplant HTN requires developing de novo HTN after kidney transplant
The most common phenotype of HTN in elderly patients isolated systolic HTN (defined as SBP ≥140 and DBP)
Linear increase in systolic and diastolic BP occurs with age until the fifth or the sixth decades of life when SBP continues increasing, but DBP tends to decrease Diastolic HTN is defined as DBP of ≥90 mmHg, with a SBP <140 mmHg, and is more common in younger,
sedentary individuals with a higher body mass index (BMI) After SPRINT trial, HTN was re-defined as (SBP) >130 or DBP >80 mmHg
A recent 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a target BP of
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
Very low pretransplant SBP (<110 mmHg) and DBP (<50 mmHg) are associated with a decrease in renal allograft loss.
During the post-transplant period, elevated BP is associated with poorer renal allograft and patient outcomes.
Cardiovascular Outcomes-Related to Post-transplant Hypertension
Kidney transplant recipients with left ventricular hypertrophy (LVH) or HFpEF have increased morbidity and mortality and are at high risk for cardiac-related events
Renal insufficiency is involved in the pathogenesis of HFpEF (126) and causes salt-sensitive HTN
Uncontrolled HTN after kidney transplantation leads to structural damage to both the renal allograft and heart eventually resulting in decreased renal and cardiac functions.
BLOOD PRESSURE MEASUREMENT
· office blood pressure: the mean of three non-invasive BP measurements
· home blood pressure monitoring: recording at least twice the daily average of two home blood pressure readings over a minimum of 4 days
· 24- h ambulatory blood pressure monitoring BLOOD PRESSURE MANAGEMENT A. Non-pharmacologic interventions: diet, exercise, and stress reduction B.PHARMACOLOGICAL: 1-Loop Diuretics:
· used for Volume control rather than BP control.
· can be used to control both volume and BP in patient with pulmonary congestion and HTN.
· increase risk of UTI during the first 5 years after kidney transplantation
2- Thiazides:
· may cause hyperglycemia, hyperuricemia, hypercalcemia, and hyponatremia
· can be used in the setting of volume overload and concomitant hypomagnesemia, to reduce the hypomagnesemic effect of CNI therapy
3- Mineralocorticoid Receptor Antagonists
· may be a new option for BP control in individual with CNI-induced HTN and proteinuria.
· Hyperkalemia is a common side effects and it may be worse in kidney transplant recipients who have CNI-induced hyperkalemia
4- Beta-Blockers
· In kidney transplant recipients, betablockers are the most common used antihypertensive medication
· has additive effect on ACEI or ARB with greater survival in kidney transplant patients on this combination compared to those who received either medication alone or neither
· they can cause proteinuria, hyperkalemia, and masking of hypoglycemic symptoms
5- Calcium Channel Blockers
· In addition to blood pressure control, they prevent post-transplant acute tubular injury (ATI) or DGF
· a recent systematic review showed that calcium channel blockers decreased graft loss and increased GFR
· can result in peripheral edema and muscle weakness especially when used in combination with steroids. Gum hyperplasia is also more common when CCB are used with CsA
6- Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor Blockers (ARB)
· Although ACEIs and ARBs provide antiproteinuric effect, they are generally not the drugs of choice during the immediate and early post-transplant periods
· they are known to decrease GFR
· can lead to regression of LVH in kidney transplant recipients
7- Alpha1-Antagonists
· rarely used as the initial or as a single antihypertensive agent in kidney transplant recipients
· there is no evidence that alpha1-antagonists provide superior antihypertensive effect or slows progression of renal allograft dysfunction when compared to other antihypertensive medications
8- Alpha2 Agonists (centrally acting)
· When used as monotherapy, methyldopa is associated with antihypertensive tolerance, edema, and weight gain
· Clonidine is also associated with weight gain and progressive resistance with continued use
· rebound HTN is common after discontinuation of clonidine C. OTHER MANAGEMENT FOR BLOOD PRESSURE
· Native Nephrectomy: for resistant HTN
· Native Renal Sympathetic Denervation
· Surgical Renal Denervation by Bilateral Native Nephrectomy
· Catheter Ablative Renal Denervation
How do you manage hypertension after kidney transplantation in your workplace?
·
Early post transplantation: be sure that patient is not overloaded, adjust CNI level. If Bp still high I would start with amlodipine and or bisoprolol if there was tachycardia or heart failure
· If the patient developed lower limbs oedema after adding CCB, I would change it to centrally acting Alpha2 Agonists, or alpha 1 blocker, in early stage
· After 1 year I may add an ACEi or ARB if the patient had L.L edema or proteinuria or polycythemia
· When I use ACEi or ab ARB, I repeat creatinine after one week, and then one month. I stop it if creatinine elevated more than 20% of the base line
· If the patient is overloaded and hypertensive, I may give thiazide or furosemide (if there is renal impairment)
saja Mohammed
2 years ago
Introduction
Hypertension Post-transplantation very common and complex pathology, many immunological and nonimmunological factors related to transplantation can lead to hypertension in addition to medication effects, in particular, CNI, transplant renal artery stenosis (TRAS), OSA, metabolic syndrome, dyslipidemia, obesity, and DM, it carries high cardiovascular risk and impacts the graft survival, post-transplant hypertension can be classified as early, immediate and late after TX, which usually associated with chronic graft dysfunction .this article review the causes, pathogenesis of hypertension post-transplantation, classification and treatment options including pharmacological and interventional angioplasty or renal denervation and native kidney nephrectomy in the resistant type of hypertension based on the available evidence from the guideline. Definition of post-kidney transplantation
The definition and prevalence Of HTN post-transplantation are quite variable between studies however target Bp should be < 130/80 Persistent high blood pressure or normotensive with medications after kidney transplantation further classification of hypertension can be categorized as persistent HTN, recovered HTN, persistent normotension, and post TX HTN, and with aging isolated systolic HTN also common, Post-transplant HTN associated with increased CVS morbidity. Post-transplant HTN
Immediate post-transplant period due to IVF peri-and postoperative time which leads to volume overload, induction immunosuppression medications like steroids with increased sympathetic over activity, rebound HTN especially those on BB, and deficient pain control also due to sympathetic overactivity Early post-transplantation Between 24-52 weeks post-TX, involve many factors
Weight gain, immunosuppression therapy (CNI, STEROIDS), hypertensive kidney donor, transplant RAS
CNI Induced HTN
Change of Vascular tone, with arteriolar vasoconstriction and reduced vasodilator
Late post-transplantation
Chronic allograft dysfunction
FBGF23
OSA
Failed native kidneys
Sympathetic overactivity
RAS , renal artery stenosis
Ramy Elshahat
2 years ago
Why we need to control Hypertension After Kidney Transplantation
• Several studies have demonstrated an association between post-transplant HTN, CV risk, and renal allograft failure.
• Opelz et al. conducted a retrospective study of 29,751 kidney transplant recipients followed for over 7 years. Increased post-transplant SBP and DBP were associated with progressively decreased renal allograft function and death-censored chronic graft failure
• There is insufficient information about CV and mortality outcomes related to isolated diastolic HTN in kidney transplant recipients. Epidemiology Of Post-transplant Hypertension
• the prevalence of post-transplant HTN has been widely reported,
• The exact prevalence is difficult to diagnose because the definition and methods of blood pressure (BP) measurement in studies didn’t share the same criteria but it has generally increased over time. This greater incidence of post-transplant hypertension may be related to the introduction of cyclosporine Definition Of Post-transplant Hypertension
· the definition of HTN in kidney transplant recipients remains controversial, and hard outcomes related to BP levels are still limited.
· A recent 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a target BP of <130/80 mmHg.
· Until there is stronger evidence of an association between BP level and outcomes in kidney transplant recipients, a BP ≥130/80 mmHg may be a reasonable definition for HTN in this population.
PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION
Immediate Post-transplant Period Rebound Hypertension
it is common practice to hold some if not all of the pre-transplant BP medications in an effort to avoid early hypotension. However, this abrupt discontinuation of antihypertensive therapy can lead to rebound hypertension, an elevated BP above pretreatment levels, as a result of sympathetic overactivity.
Beta-adrenergic agonists, clonidine (both oral and transdermal forms) and methyldopa.
2. beta-blockers Early Post-transplant Period
Calcineurin Inhibitors: The prevalence of HTN in kidney transplant recipients in the pre-CNI era of 40–50% and increased to 70 and 90% after CNI
• the vasoconstrictive effect on renal or systemic vasculature remains unclear.
• Increased renal sodium transport handling: Sympathetic nervous system activation. CSA causes sympathetic excitation and subsequent sodium retention(Sodium Chloride Cotransporter (WNK-SPAKNCC) pathway
2. . Transplant Renal Artery Stenosis (TRAS):
o It’s associated with poorer transplant outcomes and CV complications including post-transplant HTN and early treatment causes reverse those negative outcomes.
o TRAS may occur at any time after kidney transplantation but is generally diagnosed between 3 and 24 months post-transplantation( Immunological factors leading to vascular endothelial dysfunction can cause TRAS. Other transplant-related risk factors have been reported including cytomegalovirus (CMV) infection)
o Diagnosis: Renal artery angiography remains the gold standard diagnostic test for TRAS, but it is invasive and can lead to CIN. Carbon dioxide (CO2) angiography can mitigate some of the risks of CIN, but, in most cases, small amounts of IV contrast are still required to attain sufficiently detailed images.
o Three therapeutic options for TRAS are pharmacological therapy alone or pharmacologic therapy in addition to renal artery angioplasty with stenting or surgical revascularization
o Medical antihypertensive therapy may be utilized to control blood pressure. Statins and acetylsalicylic acid may also be part of pharmacological therapy although there is no clear evidence for these use specifically in TRAS
o Indication for intervention
o Patients with worsening serum creatinine and/or uncontrolled HTN attributable to TRAS
o There is no randomized controlled clinical trial (RCT) comparing the efficacy of angioplasty ± stenting vs. surgical revascularization vs. pharmacological therapy alone in the kidney transplant population.
Late Post-transplant Period
• Obstructive Sleep Apnea
• Sleep disorders Evaluation in Patients after kidney Transplantation (SLEPT) : In this study, kidney transplant patients with OSA required a significantly higher number of antihypertensive medications and tended to have higher SBP as compared to non-OSA patients
• They share the same risk factors including male gender, obesity, use of hypnotic drugs, presence of severe comorbidity (e.g., heart disease, cerebrovascular disease, peripheral vascular disease, diabetes mellitus), and impaired kidney function (indication for a sleep study)
• If any of these diseases is uncontrolled or progresses the other two conditions tend to worsen or become more difficult to manage. Therefore, appropriate management of OSA is an essential component of the antihypertensive therapy in kidney transplant recipients who later develop renal allograft dysfunction, especially with resistant HTN.
BLOOD PRESSURE MEASUREMENT:
• it may frequently be unreliable due to variation of physiologic response to internal and external stimuli as well as inappropriate BP measurement techniques.
• Reliable BP measurement should be mandatory in clinical practice and can be standardized with the following definitions
• office blood pressure (OBP): the mean of three BP measurements
• home blood pressure monitoring (HBPM): recording at least twice the daily average of two home blood pressure readings over a minimum of 4 days
• 24- h ambulatory blood pressure monitoring (24-h ABPM): dippers, non-dippers, and reverse dippers
• Compared with OBP, a 24-h ABPM led to 61% disagreement in diagnosis (58% and 3% due to masked and white-coat HTN, respectively).
• Although a 24-h ABPM can provide useful information to diagnose patterns of HTN like white coat and masked HTN, OBP and HBPM are more commonly used in clinical practice.
• Since transplant renal allografts are very sensitive to BP hemodynamic changes, HBPM appears to be a commonly utilized method of following BP after kidney transplantation. Based on study addressed by Mallamaci F. (2018): revealed a higher correlation between a 24-h ABPM and HBPM than 24-h ABPM and OBP
• Although HBPM is widely available, better correlated to 24-h ABPM, and superior to OBP when predicting hard outcomes, we used HBPM in conjunction with OBP for our kidney transplant patients to minimize misclassification of HTN diagnosis, monitor possible white coat or masked HTN, and adjust antihypertensive medications.
Blood Pressure Management
• PHARMACOLOGICAL MANAGEMENT
• there is no drug of choice for BP control after kidney transplantation.
• Several factors are involved in selecting the appropriate antihypertensive medications including immunologic and non-immunologic factors as well as the time after kidney transplantation.
• Different from the non-transplant CKD population, beta blockers and calcium channel blockers are the most frequently used combination in kidney transplant recipients. Beta-blockers provide a cardioprotective effect for kidney transplant patients, who likely have underlying CAD.
• Calcium channel blockers have the vasodilatory effect that counteracts the vasoconstrictive effect of CNIs.
• ACEIs and ARBs are not routinely used as antihypertensive medications in kidney transplant recipients. This is especially true during the early post-transplant period when baseline renal allograft function is not well-established. They can, however, be considered when there is a specific indication for their use, such as proteinuria and posttransplant erythrocytosis.
• diuretics are not generally used as the first line for BP control in kidney transplant recipients.
• we routinely use dihydropyridine calcium channel blockers and/or beta-blockers as first-line antihypertensive medications.
• Since the majority of patients do not achieve BP control during the immediate or early post-transplant period, the combination of dihydropyridine channel blockers with beta-blockers is commonly used in our transplant center.
• Once renal allograft function is established and stable, we consider adding or replacing ACEI or ARB for dihydropyridine channel blockers and beta-blockers if there are appropriate indications, such as proteinuria or posttransplant polycythemia
• Until there is strong clinical outcome evidence in terms of CV, patients, or renal allograft survival, BP targets should be individualized, taking into account immunologic and nonimmunologic factors that are contributing to HTN in each kidney transplant recipient.
• OTHER MANAGEMENT FOR BLOOD PRESSURE
a. Native Nephrectomy
The majority of these studies were notably conducted in patients with ADPKD as the cause of ESRD with resistant HTN, defined as uncontrolled BP with at least three antihypertensive medications of which one is a diuretic. Apart from renovascular and hormonal causes of secondary HTN (but should not be routine practice)
b. Native Renal Sympathetic Denervation
single-center RCT with 6-month follow-up of 18 kidney transplant recipients with resistant HTN compared (efficacy of renal sympathetic denervation as compared to medical therapy alone).
RDN group had
• a significantly decreased office SBP of 23.3 ± 14.5 mmHg
• a higher proportion of patients who converted from non-dippers to dippers. Nocturnal BP recorded with 24-h ABPM, but not daytime BP, was also lower by 10.38 ± 12.8 mmHg in the RDN group, though this was not statistically significant.
• Safety endpoints including changes in renal allograft function and renovascular complications were not different between the 2 groups. Although native RDN is effective in controlling BP, larger RCTs with a sham-control are required.
Theepa Mariamutu
2 years ago
Prevalence of Hypertension in KTR is ranging from 24-90%, occurring in patients with other metabolic diseases like diabetes mellitus, obesity, and hyperlipidaemia. It can be classified: persistent hypertension, recovered hypertension, persistent normotension and post-transplant hypertension The prevalence of persistent hypertension and post-transplant hypertension is 40% and 19% respectively.
Post-transplant hypertension can be defined as immediate-, early (24 to 52 weeks) and late- (after 1 year).
· Risk factors for hypertension in immediate post-transplant:
· Overload-due to intravenous fluids, especially in patients with delayed graft function
· use of induction agent and high dose steroids-increasing vascular resistance
· inadequate analgesia caused increased pain -due to sympathetic overactivity
· rebound hypertension -due to sudden stoppage of beta blockers and clonidine
Risk factors for hypertension in early post-transplant period:
· obesity and weight gain,
· calcineurin inhibitor use
· steroid use
· donor hypertension / if donor has a family history of hypertension
· transplant renal artery stenosis-immunological and non-immunological causes
Hypertension in late post-transplant period is associated with chronic graft dysfunction (persistent antibody mediated rejection, Interstitial fibrosis, and tubular atrophy, thrombotic microangiopathy and disease recurrence), obstructive sleep apnoea (due to sympathetic overactivity, endothelial dysfunction, and chronic volume overload), failed native kidneys, elevated FGF23 and sympathetic overactivity.
Post-transplant hypertension – associated with decreased graft survival (high systolic blood pressures) and increased mortality due to left ventricular hypertension and HFpEF.
Blood pressure measurement method could be either office BP (OBP), home BP monitoring (HBPM) or a 24-hour ambulatory BP monitoring (ABPM). A combination of OBP and HBPM is commonly used.
harmacological managements include antihypertensives like:
· Loop diuretics: Useful in control of volume overload in immediate post-transplant period, but cause hypomagnesemia and its use has been shown to be associated with increased UTI risk in first 5 years post-transplant. May be used with ACE inhibitors and ARBS in transplant renal artery stenosis.
· Thiazide diuretics: useful in patients with oedema and hypomagnesemia. Can be used in combination with CNIs (causing salt-sensitive hypertension). May cause hypercalcemia, hyperuricemia, and hyponatremia.
· Mineralocorticoid receptor antagonists: They are useful in patients with systolic dysfunction, CNI induced hypertension and proteinuria due to antiproteinuric effects and cardiovascular benefits. But their use is associated with hyperkalaemia.
· Beta blockers: most common antihypertensive used in transplant recipients. They inhibit sympathetic nervous system and decrease atherosclerotic risk (cardioprotective) but cause proteinuria, hyperkalaemia, and mask symptoms of hypoglycaemia.
· Calcium channel blockers (CCBs): Commonly used, they prevent post-transplant acute tubular injury and delayed graft function, are associated with reduced graft loss and increased GFR. The use of diltiazem is associated with elevated CNI levels. They may cause peripheral oedema, muscle weakness (when used with steroids) and gum hyperplasia.
· ACE inhibitors/ ARBs: They cause regression of LVH, are antiproteinuric and reduce occurrence of interstitial fibrosis/ tubular atrophy. But their use is associated with reduction in GFR and haematocrit. They should not be used in early post-transplant period and are useful in patients with LVH, CCF and proteinuria.
· Alpha1 antagonists: used as adjunctive drugs
· Alpha2 agonists: Control sympathetic activity. Their use is associated with weight gain, oedema and tolerance. Rebound hypertension on discontinuation take place.
Procedures and surgical interventions
Native nephrectomy: especially in patients with ADPKD
Native renal sympathetic denervation
Surgical renal denervation by bilateral native nephrectomy
Catheter ablative renal denervation.
· Transplant renal artery angiography and stenting: for TRAS with increasing serum creatinine and uncontrollable hypertension
· Surgical revascularization of transplant renal artery stenosis: if renal artery angioplasty is unsuccessful.
· Treatment of OSA: Weight reduction and use of BiPAP
How do you manage hypertension after kidney transplantation in your workplace?
In our centre, we try to avoid antihypertension and usually keep bp at high value. We prefer CCB over B blocker unless patient is tachycardia or AF post LRKT. ACE I and ARB will be introduce later probably after 3 months
Eusha Ansary
2 years ago
Post-kidney transplant HTN can be defined as persistently elevated BP or normal BP with the use of antihypertensive after a successful kidney transplant. The transplant recipient’s HTN is classified as a) Persistent HTN b) Recovered HTN c) Persistent normotension d) Post-transplant HTN Post-transplant hypertension pathophysiology and classification:
a) Immediate post-transplant period that includes peri-transplant hypervolemia, high dose steroids, rebound hypertension, and inappropriate pain control. b) Early post-transplant period about 26-50 weeks after kidney transplant and include: medications use like calcineurin inhibitors, weight gain, transplant renal artery stenosis, and hypertensive donor kidney. c) Late post-transplant period which includes fibroblast growth factors-23, chronic renal allograft dysfunction, and finally obstructive sleep apnea.
The management of hypertension. It includes: a)Lifestyle modification: The non-medications involve lifestyle modifications that have to do with diet, exercise, stress reduction. Which required for all patients.
b)The pharmacological treatment of post-transplant hypertension is a long list of medications that can be used adequately control. The drugs are-
c) Procedural or surgical interventions: 1) Native renal sympathetic denervation 2) Native nephrectomy 3) Surgical renal denervation by bilateral native nephrectomy. 4) Catheter ablative renal denervation 5) Transplant renal artery angioplasty/stenting So, hypertension post-transplant is common and must be detected early and treatment must initiate immediately to avoid loss of the graft. The most common morbidity in these patients is cardiovascular disease and hypertension. In my country, I usually use CCB and Beta-blockers in most hypertensive transplant patients.
Rahul Yadav rahulyadavdr@gmail.com
2 years ago
Summarize this article
Hypertension (HTN) is a common co-morbidity post-transplant and its prevalence ranges from 24 to 90%.
In absence of available strong evidence, BP of less than 130/80 is a reasonable target in post-transplant population.
Post-Transplant HTN is categorized as
1. Persistent HTN
2. Recovered HTN
3. Post-Transplant HTN
Causes of Post-Transplant HTN differs across different post-transplant periods and classified as:
Immediate Post Transplant Period:
1. Peri-Transplant Hypervolemia
2. High Dose steroids: Due to arterial vascular resistance from alteration in intrinsic pressor response. Threshold dose for having HTN is 20mg of steroids.
3. Rebound Hypertension: Due to sympathetic overactivity due to abrupt discontinuation especially Clonidine and Beta-Blockers.
4. Inappropriate Pain management: Sympathetic nervous system activation and stimulation of neuro-endocrine system via HPA axis leads to pain induced hypertension
Early Post-Operative Period: Between 24 to 52 weeks post-transplant
1. Weight Gain
2. CNI: Increased Vasoconstriction, Impaired Vasodilation, sympathetic excitation, and increased Na and Cl reabsorption in DCT leading to salt sensitive HTN
3. Steroids
4. Hypertensive Donor Kidney
5. Transplant Renal artery Stenosis: accounts for 1-5% Post Transplant HTN. Generally diagnosed between 3 to 24 months post-transplant. Non-Immunological causes includes vascular damage during surgery or native vascular disease in both donor and recipient artery. Immunological causes are vascular endothelial dysfunction, immune mediated vascular endothelial injury (Diffuse stenosis). Other risk factors are CMV infection, atherosclerosis.
Late Post Transplant period:
1. Chronic Renal allograft Dysfunction
2. Fibroblast Growth Factor 23
3. OSA
Blood Pressure measurement: Home blood pressure monitoring (recording at least twice the daily average of two home blood pressure reading over a min for 4 days) and office blood pressure (mean of three non-invasive BP measurement in office) is widely used for HTN diagnosis, monitor possible white coat or masked hypertension and prescribing/adjusting antihypertensive medications
HTN Management:
Lifestyle management: Diet, exercise, and stress reduction
Pharmacological management:
1. Diuretics: Not commonly used as first line.
Loop Diuretic: Mechanism of Action (MOA): Volume control and vasodilator effect.
Thiazides: MOA is inhibition of Na-Cl cotransporter in DCT. Used in CNI induced salt sensitive HTN and hypomagnesemia
2. Mineralocorticoid Receptor Antagonist: Inhibit MCR in principal cells of CD. Antiproteinuric with Hyperkalaemia as side effect. Indicated for CNI induced Hypertension and proteinuria
3. Beta-Blockers: Favored medication in Post-Transplant HTN. Mitigation of sympathetic tone and decrease proinflammatory cytokine thereby decreasing risk of atherosclerosis and is cardio protective. SE includes proteinuria, hyperkalemia, and masking of hypoglycemic symptoms.
4. CCB: MOA, Vasodilatory effects. Preferred first line for post-transplant HTN.SE, Peripheral oedema and muscle weakness especially when used along with steroids. Dihydropyridines compete with CNI as metabolized by a CYP (Cytochrome P45)3A4 isoenzyme leads to increase in both CCB and CNI exposure. Non-Dihydropyridines CCB inhibits CYP3A4 isoenzyme and significantly increases CNI level
5. ACEI/ARB: Not the first choice in immediate and early transplant period due to known effect in decrease in GFR which will add confusion. Used later when graft function stabilizes and especially in proteinuria with LVH or congestive heart failure
6. Alpha 1 Antagonist: Adjunctive therapy and rarely as initial or single antihypertensive therapy
7. Alpha 2 Agonist: MOA, stimulates Presynaptic adrenoreceptors in CNS and suppress central sympathetic activity. Rarely used as initial/single agent
Other measures for Blood pressure control
1. Native Nephrectomy: Mainly studied in ADPKD
2. Surgical renal denervation by bilateral nephrectomy
How do you manage hypertension after kidney transplantation in your workplace?
CCB and/or Beta blockers are commonly used medication in immediate and early transplant period
Diuretics are used for volume control in immediate or early post-transplant period
Once graft function stabilizes addition or replacing ACEI/ARB for Dihydropyridine CCB and betablockers if Proteinuria or post-transplant Polycythemia
Various risk factors like Obesity, OSA to be adequately treated
Advise Lifestyle modification
Amit Sharma
2 years ago
Briefly summarise this article
Hypertension in kidney transplant patients is common with prevalence ranging from 24-90%, occurring in patients with other metabolic diseases like diabetes mellitus, obesity and hyperlipidemia. It can be categorized into 4 different categories: persistent hypertension (hypertension in both pre- and post-transplant period), recovered hypertension (correction of hypertension post-transplant), persistent normotension (no hypertension pre- and post-transplant) and post-transplant hypertension (new onset hypertension after transplant). The prevalence of persistent hypertension and post-transplant hypertension is 40% and 19% respectively.
Post-transplant hypertension can be classified as immediate-, early- (first 24 to 52 weeks) and late- (after 1 year) onset hypertension.
Risk factors for hypertension in immediate post-transplant period include volume overload (due to intravenous fluids, especially in patients with delayed graft function), use of induction agent and high dose steroids (increasing vascular resistance), increased pain (due to sympathetic overactivity), and rebound hypertension (due to sudden stoppage of beta blockers and clonidine).
Risk factors for hypertension in early post-transplant period include obesity and weight gain, calcineurin inhibitor use (due to reduced vasodilatation and sympathetic nervous system activation), steroid use (if dose more than 20 mg per day), donor hypertension (or if donor has a family history of hypertension) and transplant renal artery stenosis (due to immunological and non-immunological causes).
Hypertension in late post-transplant period is associated with chronic graft dysfunction (persistent antibody mediated rejection, Interstitial fibrosis and tubular atrophy, thrombotic microangiopathy and disease recurrence), obstructive sleep apnea (due to sympathetic overactivity, endothelial dysfunction and chronic volume overload), failed native kidneys, elevated FGF23 and sympathetic overactivity.
Post-transplant hypertension is associated with decreased graft survival (especially with high systolic blood pressures) and increased mortality (due to left ventricular hypertension and HFpEF).
Blood pressure measurement method could be either office BP (OBP), home BP monitoring (HBPM) or a 24-hour ambulatory BP monitoring (ABPM). A combination of OBP and HBPM is commonly used.
Blood pressure management in kidney transplant recipients include non-pharmacological measures (lifestyle modifications – diet, exercise, weight reduction and stress reduction), pharmacological measures , and procedural or surgical interventions.
Pharmacological managements include antihypertensives like:
a) Loop diuretics: Useful in control of volume overload in immediate post-transplant period, but cause hypomagnesemia and its use has been shown to be associated with increased UTI risk in first 5 years post-transplant. May be used with ACE inhibitors and ARBS in transplant renal artery stenosis.
b) Thiazide diuretics: useful in patients with edema and hypomagnesemia. Can be used in combination with CNIs (causing salt-sensitive hypertension). May cause hypercalcemia, hyperuricemia and hyponatremia.
c) Mineralocorticoid receptor antagonists: They are useful in patients with systolic dysfunction, CNI induced hypertension and proteinuria due to antiproteinuric effects and cardiovascular benefits. But their use is associated with hyperkalemia.
d) Beta blockers: most common antihypertensive used in transplant recipients. They inhibit sympathetic nervous system and decrease atherosclerotic risk (cardioprotective) but cause proteinuria, hyperkalemia and mask symptoms of hypoglycemia.
e) Calcium channel blockers (CCBs): Commonly used, they prevent post-transplant acute tubular injury and delayed graft function, are associated with reduced graft loss and increased GFR. The use of diltiazem is associated with elevated CNI levels. They may cause peripheral edema, muscle weakness (when used with steroids) and gum hyperplasia.
f) ACE inhibitors/ ARBs: They cause regression of LVH, are antiproteinuric and reduce occurrence of interstitial fibrosis/ tubular atrophy. But their use is associated with reduction in GFR and hematocrit. They should not be used in early post-transplant period and are useful in patients with LVH, CCF and proteinuria.
g) Alpha1 antagonists: used as adjunctive drugs
h) Alpha2 agonists: Control sympathetic activity. Their use is associated with weight gain, edema and tolerance. Rebound hypertension on discontinuation take place.
Procedures and surgical interventions: These are adopted in patients with resistant hypertension, and include-
a) Native nephrectomy: especially in patients with ADPKD
b) Native renal sympathetic denervation
c) Surgical renal denervation by bilateral native nephrectomy
d) Catheter ablative renal denervation.
e) Transplant renal artery angiography and stenting: for transplant renal artery stenosis with increasing serum creatinine and uncontrollable hypertension
f) Surgical revascularization of transplant renal artery stenosis: if renal artery angioplasty is unsuccessful.
g) Treatment of OSA: Weight reduction and use of BiPAP
There is no specific antihypertensive recommended in post-transplant hypertension treatment. The treatment should be individualized.
How do you manage hypertension after kidney transplantation in your workplace?
The management of hypertension in our workplace includes emphasis on lifestyle modification (regular exercise and diet advise). The antihypertensives used in our unit include CCBs and beta blockers. Patients on clonidine pre-transplant are continued on them post-transplant and tapered later on as per the requirements. ACE inhibitors are added in proteinuric patients, keeping an eye on the creatinine levels. ACE inhibitors/ ARBS are avoided in first 3 months. If the creatinine increases with ACE inhibitor use, we rule out possibility of transplant renal artery stenosis by renal Doppler. We have not encountered any resistant hypertension requiring surgical nephrectomy. We do not have facility of renal denervation in our setup.
Last edited 2 years ago by Amit Sharma
Marius Badal
2 years ago
Briefly summarise this article
How do you manage hypertension after kidney transplantation in your workplace?
This article is giving details about the approach and management of hypertension after a kidney transplant. Cardiovascular diseases pre- and post-transplant are the most common comorbidity found in all patients. It is also present in the majority of posttransplant individuals.
Since the introduction of CNI graft survival has improved but the long-term effect has been evolving. This effect is the increased risk of mortality due to cardiovascular disease and the one of interest is hypertension. Hypertension is a usual finding in the transplant population and is the most common risk factor for CVD. The overall prevalence of posttransplant hypertension has ranged from 24 to 90%.
Post-transplant HTN is defined as a persistently elevated BP or normal BP with the use of antihypertensive after a successful kidney transplant. The transplant recipient’s HTN is classified as:
1) Persistent HTN
2) Recovered HTN
3) Persistent normotension
4) Post-transplant HTN
Post-transplant hypertension pathophysiology and classification:
1) Immediate post-transplant period that includes peri-transplant hypervolemia, high dose steroids, rebound hypertension, and inappropriate pain control.
2) Early post-transplant period about 26-50 weeks after kidney transplant and include: medications use like calcineurin inhibitors, weight gain, transplant renal artery stenosis, and hypertensive donor kidney.
3) Late post-transplant period which includes fibroblast growth factors-23, chronic renal allograft dysfunction, and finally obstructive sleep apnea.
The management of hypertension. It includes:
1) Non-medications
2) Medications
The non-medications involve lifestyle modifications that have to do with dieting, exercise, avoidance of stressful events or activities, avoiding alcohol and coffee, etc.
The pharmacological treatment of post-transplant hypertension is a long list of medications that can be used adequately control. The drugs are:
1) Anti-calcium channel blockers
2) Beta-blockers
3) ARBs and ACEIs are not frequently used in transplant patients. They have their rightful specifications, especially in patients with proteinuria and erythrocytosis.
4) Antidiuretics are not generally sued but may have indications for patients with fluid overload or to challenge the graft to respond after the patient is hydrated adequately.
5) Alpha 1 antagonists like clonidine
There are other forms of treatment that can be used but are not common practice because the above measures should be able to control the BP but if not the case the following can be attempted:
1) Native renal sympathetic denervation
2) Native nephrectomy
3) Surgical renal denervation by bilateral native nephrectomy.
4) Catheter ablative renal denervation
5) Transplant renal artery angioplasty/stenting
So, hypertension post-transplant is common and must be detected early and treatment must initiate immediately to avoid loss of the graft. The most common morbidity in these patients is cardiovascular disease and hypertension falls on the top list. Therefore, to preserve the graft it must be treated.
In my country, there aren’t many kidney transplants and my experience with using them is limited but to my knowledge gain, the above common ones are what are most likely to be used to control patients’ blood pressures.
Filipe prohaska Batista
2 years ago
It is a study talking about pre- and post-transplant hypertension and the risk groups involved, especially patients with a history of metabolic changes (diabetes mellitus, hyperlipidemia, and obesity). Post-transplant hypertension is divided into immediate, early, and late.
Cardiovascular disease is the main cause of death in this group, especially in patients using cyclosporine. Normotensive patients before and after transplantation (persistent normotensives) and those who normalized after transplantation (recovered hypertension) have the best prognosis, while persistent hypertension (already previously) and those who started after transplantation have the worst prognosis.
There is a lot of discussion about what is the appropriate blood pressure and diastolic pressure in this patient profile, but most consider it to be < 130x80mmHg.
Immediate Post-transplant period
Peri-transplant hypervolemia
High-Dose steroids
Rebound Hypertension
Innapropriate pain manegement
Early Post-transplant period
Weight gain
Calcineurin inhibitors
Steroids
Hypertensive donor kidney
Transplant renal artery stenosis
Late post-transplant period
Chronic Renal Allograft Dysfunction
Fibroblast growth factor (FGF) 23
Obstructive sleep apnea
We are aware of the high correlation between blood pressure control, renal graft function and post-transplant cardiac function. Sometimes, to obtain more reliable values, an outpatient blood pressure assessment is necessary. High differences between blood pressure values during the day suggest post-transplant hypertension and the need for treatments with lifestyle changes (diet, exercise and stress reduction), as well as the best specific pharmacological profile for each individual.
Loop diuretics – widely used in the immediate post-transplantation period and in situations such as acute pulmonary edema in non-anuric patients. High risk of hypokalemia.
Thiazides – They present hyperglycemia, hyperuricemia, hypercalcemia and hyponatremia, being generally used in patients with hypomagnesemia induced by calcineurin inhibitors.
Mineralocorticoid receptor antagonists – care should be taken due to the risk of hyperkalemia, common in this patient profile, but they have good results for the control of proteinuria and arterial hypertension after transplantation after CNI.
Beta-blockers – patients have better survival in kidney transplant patients, but have proteinuria, hyperkalemia and may mask symptoms of hypoglycemia.
Calcium channel blockers – may counterbalance the vasoconstrictor effect of CNIs due to their ability to vasodilate, improving blood pressure control and increasing renal graft survival. They may present with peripheral edema, especially with concomitant use of corticosteroids. May interfere with CNI metabolism.
ACEi and ARB – act on the renin-angiotensin axis, decreasing proteinuria and hematocrit. May improve left ventricular hypertrophy, optimizing the treatment of congestive heart failure.
Alpha1 antagonists – little impact as a monotherapy, but can optimize treatments in use as an adjuvant treatment.
Alpha 2 antagonists – related to weight gain and resistance with time of use. They are generally not used post-transplantation, but may be necessary in specific cases.
Other management for blood pressure
Native nephrectomy
Native renal sympathetic denervation
Surgical renal denervation by bilateral native nephrectomy
Catheter Ablative renal denervation
In our service, we provide all antihypertensive drugs in the public system, with the exception of alpha 1 antagonists. A multidisciplinary team plays a crucial role in the individualization of treatment.
Reem Younis
2 years ago
Briefly summarise this article
-Overall prevalence of post-transplant HTN has ranged from 24 to 90% .
– The definition of HTN in kidney transplant recipients remains controversial, and hard outcomes related to BP levels are still limited.
– A recent 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a target BP of <130/80 mmHg . Immediate Post-transplant Period
Post-transplant HTN is generally a result of external factors like transplant surgery, IV fluids, and high doses of steroids. Early Post-transplant Period
– The early post-transplant period is between 24 and 52 weeks post transplantation. Several factors contribute to HTN like weight gain,steroids ,CNI,hypertensive donor kidney,transplant renal artery stenosis. Late Post-transplant Period
-Chronic Renal Allograft Dysfunction
Common causes of renal allograft injury include acute allograft rejection—both
acute antibody-mediated—and acute cellular rejection. allograft (19).
-Fibroblast Growth Factor (FGF) 23.
-Obstructive Sleep Apnea .
-increased sympathetic activity .
-Several studies have demonstrated an association between post-transplant
HTN and renal allograft failure . Management of HTN:
–Non-pharmacologicinterventions :
-diet, exercise, and stress reduction, should always be part of treatment of HTN.
– Additionally, other interventions specific to certain etiologies of resistant HTN, such as transplant renal artery angioplasty ± stenting and treatment for OSA,
should be implemented.
-Renal sympathetic denervation of the native kidneys either by bilateral native nephrectomy or catheter ablation is also treatment option for resistant HTN in this population . PHARMACOLOGICAL MANAGEMENTS
-Beta-blockers were the most common antihypertensive medication used in this cohort followed by calcium channel blockers.
-Uses of ACEI, diuretics, and alpha blockers were about the same.
-ARB therapy was utilized least.
– ACEI and ARB are generally held following a transplant. An alpha2 agonist like clonidine, however, may need to be continued during peritransplant
period to avoid rebound HTN.
-Diuretics are not commonly used as the first line antihypertensive medication in kidney transplant recipients. They may cause volume depletion, electrolyte disturbances, and worsening renal allograft function.
– Loop diuretic use has been associated with increased risk of UTI during the first 5 years after kidney transplantation..
-Thiazides may be considered for kidney transplant recipients with CNI-induced salt-sensitive HTN and hypomagnesemia.
-MCRA may be a new option for BP control in individual with CNI-induced HTN
and proteinuria.
– The beta blocker has additive effect on ACEI or ARB with greater survival
in kidney transplant patients on this combination compared to those who received either medication alone or neither.
-The vasoconstrictive effect of CNIs leads to post-transplant HTN , calcium channel blockers are thought to be an appropriate agent for post-transplant HTN. Theoretically their vasodilatory effect can counteract the vasoconstrictive effect ofCNIs and improve BP control .
-Calcium channel blockers also prevent post-transplant acute tubular injury (ATI)
or DGF.
-ACEIs and ARBs can lead to regression of LVH in kidney transplant recipients but no an improvement in all-cause mortality .
-ACEIs and ARBs are generally not the drugs of choice during the immediate
and early post-transplant periods.
-Alpha1-antagonists are rarely used as the initial or as a single antihypertensive agent in kidney transplant recipients.
– Alpha1-antagonist may have a role as an adjunctive therapy rather than first line antihypertensive agent in transplant recipients.
– Clonidine is currently the most commonly used alpha2 agonist. When used
as monotherapy, methyldopa is associated with antihypertensive tolerance, edema, and weight gain. Clonidine is also associated with weight gain and progressive resistance with continued use.
-Clonidine is rarely used as a single antihypertensive agent following kidney transplantation. OTHER MANAGEMENT FOR BLOOD PRESSURE
Native Nephrectomy
Native Renal Sympathetic Denervation
Surgical Renal Denervation by Bilateral Native Nephrectomy
Catheter Ablative Renal Denervation How do you manage hypertension after kidney transplantation in your workplace?
In the first months ,commonly we used CCB or BB…later we add ACEi or ARBs.
Khadija Alshehabi
2 years ago
Briefly summarise this article
DEFINITION OF POST-TRANSPLANT HYPERTENSION
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation.
Kidney transplant recipients can be categorized, based upon HTN, into four groups:
· persistent HTN,
· recovered HTN
· persistent normotension
· post-transplant HTN
The European Society of Hypertension and the European Society of Cardiology guidelines defined isolated systolic in the general population as HTN as SBP>140 and DBP <90 mmHg.
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
Very low pretransplant BP (<110 / 50 mmHg) associated with a decrease in renal allograft loss. On the other hand, post-transplant elevated BP is associated with poorer renal allograft and patient outcomes.
Cardiovascular Outcomes-Related to Post-transplant Hypertension
Kidney transplant recipients with (LVH) or HFpEF have increased morbidity and mortality and are at high risk for cardiac-related events.
BLOOD PRESSURE MEASUREMENT
Reliable BP measurement should be mandatory in clinical practice and can be standardized with the following definitions:
· Office blood pressure (OBP) the mean of three non-invasive BP measurements
· Home blood pressure monitoring (HBPM) recording at least twice the daily average of two home blood pressure readings over a minimum of 4 days
· 24-h ambulatory blood pressure monitoring (24-h ABPM)
Although HBPM is available, better correlated to 24-h ABPM, and superior to OBP when predicting hard outcomes, HBPM is used in conjunction with OBP for KT patients to minimize misclassification of HTN diagnosis, monitor possible white coat or masked HTN, and adjust antihypertensive medications.
BLOOD PRESSURE MANAGEMENT
Non-pharmacologic interventions, such as diet, exercise, and stress reduction, should always be part of treatment of HTN.
Pharmacologic interventions by using the antihypertensive medications remain the cornerstone of BP control.
Procedural or Surgical interventions for certain cases of resistant HTN.
BLOOD PRESSURE CONTROL DURING PERI-TRANSPLANT PERIOD
OTHER MANAGEMENT FOR BLOOD PRESSURE
· Native Nephrectomy
In ESRD patients with resistant HTN, defined as uncontrolled BP with at least three antihypertensive medications of which one is a diuretic, secondary HTN should be considered.
· Native Renal Sympathetic Denervation
Sympathetic over activity from failed native kidneys is another mechanism that leads to resistant HTN. The effect of RDN on BP control was established
· Surgical Renal Denervation by Bilateral Native Nephrectomy
· Catheter Ablative Renal Denervation
How do you manage hypertension after kidney transplantation in your workplace?
We usually follow similar scheme as outlined in the article, diuretics mainly loop are used in the immediate post-renal transplant for volume control if required. Otherwise, the patient is kept on Ca channel blockers with/out Beta blockers for controlling BP.
We usually avoid ACE-I/ARBs until 3 months post op to provide ant-proteinuric effect if indicated.
Of course, emphasis on healthy lifestyle and salt restriction as well.
Resistant cases should be investigated fully with referral to endocrinology if warranted.
Mohamad Habli
2 years ago
Hypertension in the pre- and post-transplant period carries high risk of cardiovascular complications.
The pathogenesis of hypertension in renal transplant recipients is multifactorial including immunological and non-immunological causes. Prevalence of post-transplant HTN has ranged from 24 to 90%.
There is no agreement on the definition of hypertension between European and American societies in normal population, and so that in regards to transplant population. BP ≥130/80 mmHg may be a reasonable definition for HTN in renal transplant recipients.
In kidney transplant recipients HTN is classified into 4 categories:
1- Immediate post-transplant is hypertension that occurred in the post-operative period while patient is still hospitalized. It is usually driven by peri-transplant hypervolemia, the use of high dose steroids during induction, inappropriate pain management and rebound hypertension.
2- Early Post-transplant hypertension is defined as hypertension that occur in the period between 24 and 52 weeks post-transplantation
Development of hypertension in this period is attributed to weight gain (with resolution of uremia, patients have better appetite which is also increased by steroid use). CNI as a mainstay therapy for maintenance immunosuppression is a well-established cause of hypertension. Steroids are also common cause of hypertension by fluid retention and vasoconstriction. One should be also aware of graft related causes of hypertension that include hypertensive donor kidney and Transplant Renal Artery Stenosis (TRAS).
3- Late Post-transplant Period: In addition to factors that contribute to the development of hypertension in the early post-transplant period, additional factors may contribute to HTN in the late post-transplant period.
These include: Chronic Renal Allograft Dysfunction, altered levels of Fibroblast Growth Factor (FGF) 23 and Obstructive Sleep Apnea
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
– Very low pretransplant SBP (<110 mmHg) and DBP (<50 mmHg) are associated with a decrease in renal allograft loss
– In the post-transplant period, elevated BP is associated with poorer renal allograft and patient outcomes. Several studies have demonstrated an association between post-transplant HTN and renal allograft failure.
BP measurement is achieved with 3 different approaches:
1- Office blood pressure (OBP): the mean of 3 non-invasive BP measurements
2- Home blood pressure monitoring (HBPM): measurement at least twice, the daily average of two home BP readings over at least 4 days
3- 24-h ambulatory blood pressure monitoring (24-h ABPM): 24-h ABPM is the gold standard for the diagnosis of white coat and masked HTN
Hypertension management
Treatment is divided into medical and surgical, based on the underlying causes. Medical treatment is further subdivided into pharmacological and non-pharmacological.
Dr. Tufayel Chowdhury
2 years ago
Hypertension is one of the most common cardiovascular comorbidities along with other metabolic diseases.
Post kidney transplant HTN can be defined as a persistently elevated BP or normotension with the use of antihypertensive medication after successful kidney transplantation.
In this reveiw , post kidney transplation HTN refers to persistent and de novo post transplant HTN.
Causes:
Immediate post transplant period:
Peri transplant hypervolemia- Hypervolemia is significantly associated with elevated systolic, diastolic and mean arterial pressure
High dose steroids
Rebound hypertension may occur due to sudden stoppage of clonidine and beta blocker
Inappropriate pain management may causes HTN via sympathetic nervous system activation
Early post transplant period:
This means HTN in between 24 to 52 weeks of post transplantation. Causes are:
1.Weight gain : Positive fluid intake from intra and post operative iv fluids is associated with post transplant HTN.
2.Calcineurin inhibitors: Both increased vasoconstriction and impaired vasodilation. Increased renal sodium transport handling is another cause.
Choices of medications depends upon patients characteristics, tolerability, medications side effects
Surgical interventions
Transplant renal; artery angioplasty with or without stenting
CPAP
Bilateral native vnephrectomy
Native renal dennervation
Ghalia sawaf
2 years ago
DEFINITION OF POST-TRANSPLANT HYPERTENSION
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation.
But what is a normal BP level?
We can categorize kidney transplant recipients into four groups:
persistent HTN,
recovered HTN,
persistent normotension,
post-transplant HTN.
guidelines defined isolated systolic HTN in the general population as SBP 140 and DBP <90 mmHg . This is the most common phenotype of HTN in elderly patients
PATHOGENESISOFPOST-TRANSPLANT HYPERTENSION .
Immediate Post-transplant Period
Peri-transplant Hypervolemia
High-Dose Steroids
Rebound Hypertension
Inappropriate Pain Management
2. Early post-transplantation
Weight Gain
Calcineurin inhibitors
Steroid
Hypertensive donor kidney
Transplant renal artery stenosis
3. Late post-transplantation
Chronic renal allograft dysfunction
Fibroblast growth factor 23
Obstructive sleep apnea
Failed native kidneys
Sympathetic overactivity
Cardiovascular Outcomes-Related to Post-transplant Hypertension
HTN is one of the most important risk factors for heart failure, particularly heart failure with preserved ejection fraction (HFpEF) .
Kidney transplant recipients with (LVH) or HFpEF have increased morbidity and mortality and are at high risk for cardiac-related events
BLOOD PRESSURE MEASUREMENT
office blood pressure (OBP);
home blood pressure monitoring(HBPM),
and 24h ambulatory blood pressure monitoring (24-h ABPM)
Physiological decreases in nocturnal BP further classifies patients into
dippers,
non-dippers,
and reverse dipper
decrease in nocturnal reduction in SBP was associated with a lower renal allograft function.
A 24-h ABPM can address and assist with the common misclassification of HTN diagnosed traditionally by OBP or HBPM.
BLOODPRESSURECONTROLDURING PERI-TRANSPLANT PERIOD Antihypertensive Medications
In ESRD secondary to ADPKD, the mechanism of HTN from failed kidneys is related to intrarenal renin instead of systemic renin .
In kidney transplantation, the presence of failed native kidneys is associated with post-transplant resistant HTN.
ACEIs and native nephrectomy may need to be considered.
Native Renal Sympathetic Denervation
sympathetic over activity from failed native kidneys is another mechanism that leads to resistant HTN.
The effect of RDN on BP control was established
Surgical Renal Denervation by Bilateral Native Nephrectomy
Complete RDN can be performed by bilateral native nephrectomy
Although native nephrectomy can improve posttransplant HTN, both pre- and post-transplant native nephrectomy can lead to surgical complications, which can cause impaired renal allograft function.
Catheter Ablative Renal Denervation
complete RDN by bilateral native nephrectomy in kidney transplant recipients is invasive and carries a risk of additional operation, it should be reserved for selected patients.
In our medical center
Immediately after transplantation, especially when the patient has Hypervolemia we use diuretics (Furosemide)
Persistent hypertension in the early post-transplant period we use CCB
After 3 months we use ACE inhibitor or ARBs for those who have proteinuria
Abdullah hindawy
2 years ago
This article review talk about hypertension in posttransplant patients cause greater incidence of hypertension after transplantation and outcomes after kidney transplantation and try to give a good defenetion of hypertension after transplantation.
The best defenetion by amirecan college of heart disease a blood pressure more than 130/80 is a good defenetion.
Type of hypertension is also mention and divided to four majour types :
1_persistant hypertension
2_recovered htn.
3_persistant normotensive.
4-post-transplant hypertension.
Pathogenesis ,:
Immediate:
because of iv fluids
Induction medication and steroids.
Rebound hypertension
Inadequate pain controll.
Early:
Weight gain.
Cn ihibitors
Renal artery stenosis
Late:
Chronic allograft dysfunction.
Fgf 23
Obstructiv sleep apnea.
Symptomatic overactivity.
Blood pressure management.
Divided to pharmacological and non-pharmacologic
Exercise,diet, stress reduction
Drug treatment :
Depend on the patient age and characteristic, tolerance, and medication side effect.
1- Duiretic : especially loop Duiretic better for volume control .
Furosemide is the most common used .
Its use is individually
Thiazide : uncommonly use to avoid its metabolic effects.
Maybe beneficial in cn inhibitors hypertension and decrease hyperkalemia
.
Mineral corticosteroids antagonist:
May have cv benefits and decresse protienurea.
Hyperkalemia restrict its use.
Calcium channel blockers:
It is an appropriate choice for posttransplant patients.
Vasodilation effect against cu inhibitors vasoconstriction.
Prevent atn in some study
So it is a preferred agent in transplanted patients.
Pereferal edema ,drug to drug reactions shoud be in consideration.
Angiotensin converting enzyme inhibitors
(Acei -Arbs):
The most important effect is decreasing protienurea.
Also benefit in reducing interstitial fibrosis and tubular atrophy and lvh patients
However ,they are not the drug of choice in early and immediately transplant because they are known to cause decrease in eGFR .
Alpha1 antagonists:
It is rarley used cause .
Alpha 2 agoonists :
Centrally action
Not preferred agents
In conclusion :
Beta blockers and calcium channel blockers are the main therapy for transplanted patient.
Other nopharmacological treatment are available
Catheter ablative renal denervation and syrgical renal denervation by bilaterally nephroctomy .
How do you managment hypertension in your workplace ?
As this article we mainly depend on the tow agents
Calcium chanel blockers and betablockers and use Duiretic as nedded for volume oveload patient
Some patiens may have specific situation make us use another agents (heart failure _ protienurea)so we treat these kind of patients as appropriate.
amiri elaf
2 years ago
# Briefly summarise this article
# EPIDEMIOLOGY OF POST-TRANSPLANT HTN
*The prevalence of post-transplant HTN has been increased over time, maybe related to the introduction of cyclosporine (CsA). * Overall prevalence of post-transplant HTN has ranged from 24 to 90%.
# DEFINITION OF POST-TRANSPLANT HTN
*Defined as a persistently elevated BP or norm tension with use of antihypertensive medications after successful kidney transplantation, however, different studies have defined post transplant HTN with different cutoff levels for systolic and diastolic blood pressure and different requirements for the use of antihypertensive medications.
* Kidney transplant recipients classified into 4 groups:
1)Persistent HTN (occurs in patients with HTN both in the pre- and post transplant periods 40%)
2)Recovered HTN (only during the pre- but not the post-transplant period 28%)
3)Persistent norm tensions (have no history of HTN preceding transplant and remain normotensive post-transplant 13%)
4)Post-transplant HTN (requires developing de novo HTN after kidney transplant 19%).
*Isolated HTN( systolic and diastolic) occur after KT.
*The European Society of Hypertension and the European Society of Cardiology guidelines defined isolated systolic HTN as SBP>140 and DBP <90 mmHg, most common HTN in elderly patients.
The pathogenesis involves in both intrinsic alterations resulting from normal aging process accompanied
by development of modifiable risk factors leading to increased arterial stiffness
*Diastolic HTN is defined as DBP of >90 mmHg, with a SBP <140 mmHg, and is more common in younger with higher (BMI).
*A recent 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines
recommend a target BP of <130/80 mmHg. Until there is stronger evidence of an association between BP level and outcomes in kidney transplant recipients, a BP >130/80 mmHg may be a reasonable definition for HTN in this population.
# PATHOGENESIS OF POST-TRANSPLANT HTN
# Immediate post transplantation
*Peri transplant hypervolemia
*Induction immunosuppressive medications
*Rebound hypertension
*Inadequate pain control
# Early post transplantation: (It is time between 24 and 52 weeks post-transplantation).
*Weight gain (Between 6- and 12-months post-transplantation)
*Calcineurin inhibitors(The prevalence of HTN in KT is between 70 and 90%, which is greater than the pre-CNI era of 40–50%. There are two main mechanism of CNI-induced post-transplant HTN resulting from interfering vascular tone and renal sodium transport handling.
*Steroids( may result from alterations in intrinsic pressor response leading to arterial vascular resistance)
*Hypertensive donor kidney
*Transplant renal artery stenosis (TRAS)
May occur at any time after KT but is generally diagnosed between 3 and 24
months post transplantation. Unlike (RAS) in non-transplant patients, pathogenesis of TRAS is
complex and involve:
1) Non-immunological factors include vascular damage at the time of surgical anastomosis between the donor renal artery and recipient artery as well as the presence of native vascular diseases in both donor and recipient arteries
2) Immunological factors leading to vascular endothelial dysfunction can cause
TRAS.
3) Cytomegalovirus (CMV) infection
*Three therapeutic options for TRAS are pharmacological therapy alone or pharmacologic therapy in addition to renal artery angioplasty with stenting or surgical revascularization.
*For pharmacological therapy, ACEI or ARB plus diuretics are effective regimen for BP control, but it is limited by reducing the renal function. Statins and acetylsalicylic acid may also be part of pharmacological therapy.
*Pharmacological therapy and angioplasty is preferred procedure when TRAS is recent, linear, and distal.
*Surgical revascularization is performed primarily in kinking and proximal TR
# Late post transplantation
*Chronic renal allograft dysfunction
*Fibroblast growth factor 23
*Obstructive sleep apnea
*Failed native kidneys
*Sympathetic over activity
# OUTCOMES OF HTN POST KT
* Very low pretransplant BP (<110 / 50 mmHg) associated with a decrease in renal allograft loss.
*Post-transplant elevated BP is associated with poorer renal allograft and patient outcomes
*HTN increase the of heart failure, particularly heart failure with preserved ejection fraction (HFpEF), (LVH) and so increased morbidity and mortality PKT.
*The cardio-renal dysfunction can result from salt and volume overload
# BLOOD PRESSURE MEASUREMENT
*Reliable BP measurement should be mandatory in clinical practice and can be standardized with the following definitions
1) Office blood pressure (OBP) the mean of three non-invasive BP measurements
2) Home blood pressure monitoring (HBPM) recording at least twice the daily average of two home blood pressure readings over aminimum of 4 days
3)24-h ambulatory blood pressure monitoring (24-h ABPM) which provides the average of both day and night BP readings
*HBPM is available, better correlated to 24-h ABPM, and superior to OBP when predicting hard outcomes, the used of HBPM in conjunction with OBP for KT patients to minimize misclassification of HTN diagnosis, monitor possible white coat or masked HTN, and adjust antihypertensive medications.
# BLOOD PRESSURE MANAGEMENT
* Non-pharmacologic interventions, such as diet, exercise, and stress reduction, should always be part of treatment of HTN.
* Pharmacologic interventions by using the antihypertensive medications remain the cornerstone of BP control.
*Surgical interventions
# PHARMACOLOGICAL MANAGEMENTS use of Antihypertensive Medications
*Diuretics
Not commonly used as the first line antihypertensive medication in KT recipients, due to volume depletion, electrolyte disturbances, and worsening renal allograft function, they are indicated in the peri transplant period.
*Loop Diuretics
Volume control is the indication for loop diuretics in KT recipients, during immediate and early post-transplant periods. Associated with increased risk of UTI during the first 5 years after K.
Furosemide is the most commonly used loop diuretic.
*Thiazides
Commonly used antihypertensives, but uncommon in KT recipients because of
Their S/E which include hyperglycemia, hyperuricemia, hypercalcemia, and Hyponatremia, theoretically control CNI-induced HTN. Since CNI-induced HTN is salt sensitive
*Mineralocorticoid Receptor Antagonists
Have CV benefits and antiproteinuric effect but are not used antihypertensives in KT recipients, especially those with impaired renal allograft
*Beta-Blockers
The cardioprotective effects and survival benefit of beta-blockers make them a favored medication in the general and ESRD populations
In KT recipients, has additive effect on ACEI or ARB with greater survival on this combination compared to those who received either medication alone or neither
Beta-blockers decrease proinflammatory cytokines, which are known to increase the risk for atherosclerosis.
The S/E are proteinuria, hyperkalemia, and masking of hypoglycemic symptoms.
*Calcium Channel Blockers
Can result in vascular vasodilation, since the vasoconstrictive effect of CNIs leads to post-transplant
HTN, it is suitable agent for post-transplant HTN. Also prevent post-transplant acute tubular injury (ATI) or DGF.
Although it provide better renal allograft function, several studies showed no difference in terms of BP control when using verapamil compared to enalapril or doxazosin
Calcium channel blockers
The S/E are peripheral edema and muscle weakness especially when used in combination with steroids. Gum hyperplasia when used with CsA. Although dihydropyridine calcium channel blockers do not inhibit the cytochrome P450 (CYP) 3A4 isoenzyme, leads to increase in both calcium channel blocker and CNI
exposure levels.
*Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor
Blockers (ARB)
ACEIs and ARBs are antihypertensive agents with known antiproteinuric effect, eGFR, and hematocrit, they can lead to regression of LVH in kidney transplant recipients, but they are not the drugs of choice during the immediate and early post-transplant periods, because they are decrease GFR. This S/E is reversible, but it leads to a confusion early on differentiating their role from other causes of renal allograft dysfunction and may lead to unnecessary invasive investigation, e.g. biopsy.
*Alpha1-Antagonists
Rarely used as the initial or single antihypertensive in KT recipients, they reduce BP by decreasing peripheral vasoconstriction
Alpha1-antagonist may have a role as an adjunctive therapy rather than first line antihypertensive agent
in transplant recipients.
*Alpha2 Agonists
Centrally acting work on presynaptic alpha2 adrenoceptors in the CNS and suppress central sympathetic activity and lowers BP.
Two of the oldest alpha2 agonists, methyldopa and clonidine, have long been used for BP control. methyldopa when used as monotherapy, is associated with antihypertensive tolerance, edema, and weight gain.
Clonidine is also associated with weight gain and progressive resistance and is rarely used as a single antihypertensive agent following KT due to rebound HTN after discontinuation
# In summary, there is no drug of choice for BP control after KT. Several factors are involved in selecting the appropriate antihypertensive medications include immunologic and non-immunologic factors as well as the time after KT. Bet ablockers and calcium channel blockers are the most frequently
used combination in KT recipients.
Beta-blockers provide a cardioprotective for CAD.
Calciumchannel blockers have vasodilatory effect that counteracts the vasoconstrictive effect of CNIs ACEIs and ARBs, are not routinely used in KT during the early post-transplant period when baseline renal allograft function is not well-established can be considered when there is a specific indication such as proteinuria and posttransplant erythrocytosis.
Elevated serum creatinine from ACEI or ARB therapy, although reversible, is the main reason
they are avoid.
Diuretics are not the first line for BP control in kidney transplant recipients. It may be used for volume control at immediate or early post-transplant.
OTHER MANAGEMENT FOR BLOOD PRESSURE
*Native Nephrectomy
In ESRD patients with resistant HTN, defined as uncontrolled BP with at least three antihypertensive medications of which one is a diuretic, secondary HTN should be considered.
*Native Renal Sympathetic Denervation
Done in sympathetic overactivity from failed native kidneys is another mechanism that leads to resistant HTN
The effect of RDN on BP control was established
*Surgical Renal Denervation by Bilateral Native Nephrectomy
*Catheter Ablative Renal Denervation
# How do you manage hypertension after kidney transplantation in your work place?
For measurement of blood pressure we use office BP and home BP monitoring, in very rare cases we may need 24-h ABPM
Non-pharmacologic management like control the diet, exercise, and stress reduction should be done for all patients.
Calcium Channel Blockers and or Beta-Blockers are used as first-line during the immediate or early post-transplant period.
In some cases one or more additional drug/ drugs can be added like Alpha2 Agonists ( methyldopa), Doxazosin. Diuretics may be used for volume control at immediate or early post-transplant.
ACEI or ARB should be stopped before one week of transplantation and reintroduce only after 3 monthes when there is indication.
Wadia Elhardallo
2 years ago
Briefly summarise this article
Introduction:
· Cardiovascular diseases are the leading cause of mortality in post-transplant patients, and Hypertension is one of the most common cardiovascular co-morbidities (prevalence ranged from 24 to 90%) it’s important to diagnosed and properly managed.
· Its define as a persistently elevated BP or normotension with use of antihypertensive medications *as SBP ≥140 and DBP <90 mmHg in most of the society guidelines . and divided to 4 types depending on BP status pre transplant: persistent HTN, recovered HTN, persistent normotension, and post-transplant HTN.
Depending on timing to transplantation factors contributed to raise in blood pressure vary: Immediate Post-Transplant Period: ü Peri-transplant hypervolemia ü Induction immunosuppressive medications ü Rebound hypertension ü Inadequate pain control
Early Post-Transplant Period: define as between 24 and 52 weeks’ post-transplantation:
ü Weight gain ü Calcineurin inhibitors ü Steroids ü Hypertensive donor kidney ü Transplant renal artery stenosis
Late Post-Transplant Period:
ü Factors of early post-transplant above ü Chronic renal allograft dysfunction ü Fibroblast growth factor 23 ü Obstructive sleep apnea ü Failed native kidneys ü Sympathetic overactivity
These factors might also be classified as Immunological factors including: DGF, Immunosuppression (CNI, Corticosteroids), Acute or chronic rejection Non-immunological Factors: ü Surgical related: Intraoperative volume administration, Transplant renal artery stenosis ü related to the Donor: Hypertensive kidney, Family history of HTN in donor, Transplant renal artery stenosis ü related to the Recipient: Pre-existing HTN, Renal allograft dysfunction, Dietary sodium intake, Metabolic syndrome, TRAS, OSA, Failed native kidneys, Sympathetic over activity
Blood Pressure Management: target ≤130/80 Non-pharmacologic: ü Dietary control ü Life style modification: exercise, and stress reduction
Pharmacological: antihypertensive medications:
Diuretics : not the first line Loop ,Thiazide: · Used for volume control · May use with ACEI or ARB in TRAS · Renal sodium excretion defect in CsA-induced HTN
CCB calcium channel blocker · Afferent arteriolar vasodilatation · May improve renal allograft function and lower DGF but inconclusive *Non-dipyridamole CCB is CYP450 inhibitor and increases CNI level ACEI/ARB · Anti-proteinuric · Cardioprotection · May use with diuretic in TRAS
Beta-blockers: cardioprotection
Mineralocorticoid receptor antagonists: – Systolic dysfunction – Safe with using ACEI and ARB but increase hyperkalaemia
Alpha1 antagonist :Generally, not the first line Alpha2 agonist · Lower plasma renin activity that modulated renal vascular resistance and lower MAP. · No change in GFR and effective renal plasma flow.
Other Interventions: for resistant HTN: Specific to certain etiologies, such as Transplant Renal Artery Angioplasty ± Stenting Bilateral Native Nephrectomy Renal sympathetic denervation
How do you manage hypertension after kidney transplantation in your workplace?
During perioperative time: close monitor to BP, with adequate pain control to avoid low or high reading. if needed parenteral antihypertensive medication can be used (labetalol example) At hospital discharge advice about weight control, salt low, and general dietary plan with nutritionist Follow up visit and BP regular measuring to diagnose any HTN early. When BP reading is high: looking for drug level, assessment of graft function, volume status and all other possible factors Medication: CCB is commonly used as first line, we avoid ACEi specially at early post-transplant period so not to be confused if creatinine readings start to rise.
Huda Saadeddin
2 years ago
Hypertension is one of the most common cardiovascular co-morbidities after successful kidney transplantation.
The pathogenesis of post-transplant hypertension is complex and is a result of the interplay between immunological and non-immunological factors,which can be divided intoimmediate, early, and late post-transplant periods.
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation.
it can be divided into four groups: persistent HTN, recovered HTN, persistent normotension, and post-transplant HTN. Persistent HTN occurs in patients with HTN both in the pre- and posttransplant periods, whereas patients with recovered HTN have HTN only during the pre- but not the post-transplant period. Persistent normotensive patients have no history of HTN preceding transplant and remain normotensive post-transplant. Post-transplant HTN requires developing de novo HTN after kidney transplant
The European Society of Hypertension and the European Society of Cardiology guidelines defined isolated systolic HTN in the general population as SBP ≥ 140 and DBP <90 mmHg , new BP guidelines and re-defined HTN for the general population as systolic blood pressure (SBP) >130 or DBP >80 mmHg
main causes of of post transplant HTN are classified into :
immediate post transplant
peritransplant HTN
induction immunosuppressive medications
rebound HTN
inadquate pain control
early post transplantation
weight gain
calcineurin inhibitors
steriods
HTN donor kidney
transplant RAS
late post transplantation
chronic renal allograft rejection
fibroblast growth factor 23
OSA
failed native kidney
sympathetic over activity
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
Pre-transplant BP is associated with renal allograft and patient survival outcomes after kidney transplantation. Very low pretransplant SBP (<110 mmHg) and DBP (<50 mmHg) are associated with a decrease in renal allograft loss. Specifically during dialysis lower pre- and post-dialysis DBP are associated with better patient survival post-transplantation
Several studies have demonstrated an association between post-transplant HTN and renal allograft failure.
BLOOD PRESSURE MANAGEMENT
Non-pharmacologic interventions, such as diet, exercise, and stress reduction, should always be part of treatment of HTN but pharmacological intervention remains the cornerstone of BP control in this population. Additionally, other interventions specific to certain etiologies of resistant HTN, such as transplant renal artery angioplasty ± stenting and treatment for OSA, should be implemented. Renal sympathetic denervation of the native kidneys either by bilateral native nephrectomy or catheter ablation is also treatment option for resistant HTN in this population .
there is no drug of choice for BP control after kidney transplantation. Several factors are involved in selecting the appropriate antihypertensive medications include immunologic and non-immunologic factors as well as the time after kidney transplantation.
Different from the non-transplant CKD population, betablockers and calcium channel blockers are the most frequently used combination in kidney transplant recipients. Beta-blockers provide a cardioprotective effect for kidney transplant patients, who likely have underlying CAD.Calcium channel blockers have vasodilatory effect that counteracts the vasoconstrictive effect of CNIs .
Similarly to ACEIs and ARBs, diuretics are not generally used as the first line for BP control in kidney transplant recipients. It may be used for volume control at immediate or early post-transplant.
Management for OSA and interventions for resistant HTN, such as transplant renal artery angioplasty ± stenting, bilateral native nephrectomy, and native RDN, remain options for resistant HTN in selected kidney transplant recipients. There is no conclusive BP target for this population and therapy targets need to be individualized.
Mu'taz Saleh
2 years ago
Hypertension is one of the most common cardiovascular co-morbidities after
successful kidney transplantation
The pathogenesis of post-transplant hypertension is complex and is a result of the interplay between immunological and non-immunological factors
Post-transplant hypertension can be divided into immediate, early, and late post-transplant periods.
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation.
the presence or absence of HTN during the pre-kidney transplant period
may further categorize kidney transplant recipients into
four groups:
persistent HTN,
recovered HTN,
persistent normotension,
post-transplant HTN
PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION :
1- Immediate Post-transplant Period
Peri-transplant Hypervolemia
High-Dose Steroids
Rebound Hypertension
Inappropriate Pain Management
2- Early Post-transplant Period ( 26–50 weeks after kidney transplantation )
Weight Gain
Calcineurin Inhibitors
Hypertensive Donor Kidney
Transplant Renal Artery Stenosis (TRAS)
3- Late Post-transplant Period
Chronic Renal Allograft Dysfunction
Fibroblast Growth Factor (FGF) 23
Obstructive Sleep Apnea
BLOOD PRESSURE MANAGEMENT
Non-pharmacologic interventions, such as diet, exercise, and stress reduction,
PHARMACOLOGICAL MANAGEMENTS
there is no drug of choice for BP control after kidney transplantation. Several factors are involved in selecting the appropriate antihypertensive medications include
immunologic and non-immunologic factors as well as the time
after kidney transplantation.
Different from the non-transplant CKD population, betablockers and calcium channel blockers are the most frequently used combination in kidney transplant recipients. ACEIs and ARBs, on the other hand, are not routinely used antihypertensive medications in kidney transplant recipients. They can, however, be considered when
there is a specific indication for their use, such as proteinuria and posttransplant erythrocytosis. .
diuretics are not generally used as the first line for BP control in kidney transplant recipients. It may be used for volume control at immediate or
early post-transplant.
EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION
Depending on the definition and methods of blood pressure (BP) measurement utilized
has ranged from 24 to 90%
DEFINITION OF POST-TRANSPLANT HYPERTENSION
a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation.
kidney transplant recipients categorized into four groups:
persistent HTN
recovered HTN
persistent normotension
post-transplant HTN.
The European Society of Hypertension and the European Society of Cardiology guidelines defined isolated systolic HTN in the general population as SBP ≥140 and DBP <90 mmHg
diastolic HTN is defined as DBP of ≥90 mmHg, with a SBP <140 mmHg, and is more common in younger
recent 2017 (ACC/AHA) guidelines recommend a target BP of <130/80 mmHg
Pathogenesis of post-kidney transplant hypertension is divided into
■ immunological factors
▪︎ Renal allograft dys function ( DGF , rejection )
▪︎ Immunosupression ( CNi , steroid )
■ Non immunological factors
▪︎ Donor ( hypertensive kidney , TRAS , family history of hypertension )
▪︎ Surgical ( intraoperative volume administration , TRAS )
▪︎ Recipiant ( pre-existing HTN , renal allograft dysfunction , diatery sodum intake , metabolic syndroms , OSA , TRAS , failed native kidney , sympathic overactivity )
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
during dialysis lower pre- and post-dialysis DBP are associated with better patient survival post-transplantation
During the post-transplant period, elevated BP is associated with poorer renal allograft and patient outcomes
Cardiovascular Outcomes-Related to Post-transplant Hypertension
HTN is a risk factors for heart failure with preserved EF
Uncontrolled HTN after kidney transplantation leads to structural damage to both the renal allograft and heart eventually resulting in decreased renal and cardiac functions.
BLOOD PRESSURE MEASUREMENT
BP standardized with the following definitions:
Office BP :
the mean of three non-invasive BP measurements
HBPM :
recording at least twice the daily average of two home blood pressure readings over a minimum of 4 days
24-h ABPM
wearing an electronic blood pressure measurement device to record and averages multiple readings over a 24 h period
Physiological decreases in nocturnal BP further classifies patients into dippers, non-dippers, and reverse dippers.
There is a significant decrease in the nocturnal reduction SBP after kidney transplantation and was associated with a lower renal allograft function.
Although a 24-h ABPM can discover white coat and masked HTN, OBP and HBPM are more commonly used in clinical practice.
There is a higher correlation between a 24-h ABPM and HBPM than 24-h ABPM and OBP and nighttime elevation in SBP exhibited decreased graft function
association
An elevated 24-h average SBP was significantly associated with graft loss, cardiovascular events and death over a 5-year follow-up period in kidney transplant recipients with diabetes, lower eGFR, proteinuria, young age, and female
BLOOD PRESSURE MANAGEMENT
Non-pharmacologic interventions, such as diet, exercise, and stress reduction
pharmacological intervention remains the cornerstone of BP control in this population.
** Diuretics are not commonly used as the first line antihypertensive medication in kidney transplant recipients
Volume control rather than BP control is the indication for loop diuretics in kidney transplant recipients
Thiazides may be considered for kidney transplant recipients with CNI-induced salt-sensitive HTN and hypomagnesemia.
metabolic side effects which include hyperglycemia, hyperuricemia, hypercalcemia, and hyponatremia
Mineralocorticoid Receptor Antagonists MCRA may be a new option for BP control in individual with CNI-induced HTN and proteinuria.
** Beta-Blockers
mechanism is via mitigation of the sympathetic nervous system in failed native kidneys and decrease proinflammatory cytokines, and atherosclerosis
The side effects, including proteinuria, hyperkalemia, and masking of hypoglycemic symptoms.
** Calcium Channel Blockers
their vasodilatory effect can counteract the vasoconstrictive effect of CNIs and improve BP control
It also prevent post-transplant ATN or DGF
It can result in peripheral edema and muscle weakness
It leads to increase in both calcium channel blocker and CNI exposure levels.
** Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor Blockers (ARB)
Although ACEIs and ARBs provide antiproteinuric effect, they are not the drugs of choice during the immediate and early post-transplant HTN
** Alpha1-Antagonists
clonidine is often restarted and be tapered off during early post-transplant period. But it is rarely used as a single antihypertensive agent
certain interventions such as
transplant renal artery angioplasty ± stenting
treatment for OSA
Renal sympathetic denervation of the native kidneys
bilateral native nephrectomy
catheter ablation
In our centre
We use duretics for patients with hypervolemia
In case of patient with HTN first 3 months of transplantation we use CCBs and BBs
After 3 months of transplantation we use ACEi and ARBs especially if the patient has protienuria or polycythemia
HBPM may used to in addtion to office BP readings for the diagnosis high BP in the kidney transplant population.
Abdul Rahim Khan
2 years ago
Briefly summarise this article
Hypertension is common in patients with obesity, dyslipidemia and diabetes. It is an important cause of morbidity after kidney transplant. The pathogenesis is complex and may be related to immunological and non immunological factors. This articles discusses the pathogenesis, timing of intervention and types of management options.
Post transplant hypertension can be divided into:
Immediate post transplant period
Causes can be-
Peri operative hypervolemia
High dose steroids
Rebound hypertension
Inappropriate pain management
Early post transplant period
Causes can be –
weight gain
CNI
TRAS- transplant renal artery stenosis.
Hypertensive donor kidneys
Late post transplant period
Causes can be –
Chronic allograft dysfunction
FGF- Fibroblastic growth factor
Obstructive sleep apnoea
Management
The target blood pressure should be at 130/80 mm Hg
Treatment is both pharmacological and non pharmacological.
Exercise, healthy diet and less stress can help.
Medical therapy-
includes diuretics , calcium channel blockers, ACEI and ARBi, alpha blockers, aldosterone antagonists, alpha2 agonists.
Surgical options can be native Nephrectomy, Angioplasty and stenting in TRAS, denervation, catheter ablative renal denervation,
In conclusion, hypertension is a common disease in ESRD and pathogenesis is complex. Clinicians should take into account transplant and immunology while making choice of antihypertensive agents. New surgical modalities to treat hypertension can be helpful too.
abosaeed mohamed
2 years ago
Introduction:
cardiovascular diseases (CVD) is the leading cause of morbidity and mortality in kidney transplant recipients . Hypertension (HTN) is a usual finding in this population and one of the most common risk factors for CVD .
EPIDEMIOLOGY:
· Overall prevalence of post-transplant HTN has ranged from 24 to 90 %
· the prevalence of post-transplant HTN has been widely reported, and it has generally increased over time. This greater incidence of post-transplant hypertension maybe related to the introduction of cyclosporine
DEFINITION :
– definition of HTN in kidney transplant recipients remains controversial .
– In addition to the defining normal BP levels, the presence or absence of HTN during the pre-kidney transplant period may further categorize kidney transplant recipients into four groups :
1-persistent HTN
2-recovered HTN
3- persistent normotension
4-post-transplant HTN.
– The European Society of Hypertension and the European Society of Cardiology guidelines defined isolated systolic HTN in the general population as SBP ≥140 and DBP <90 mmHg . This is the most common phenotype of HTN in elderly patients .
– alternatively, diastolic HTN is defined as DBP of ≥90 mmHg, with a SBP <140 mmHg, and is more common in younger, sedentary individuals with a higher body mass index (BMI) .
– new BP guidelines and re-defined HTN for the general population as systolic blood pressure (SBP) >130 or DBP >80 mmHg .
– in kidney transplant recipients, a BP ≥130/80 mmHg may be a reasonable definition for HTN in this population
– Tighter BP control with BP <125/75 if proteinuria > <125/75 in the patient with proteinuria >1 g/day
PATHOGENESIS :
1- immediate post transplant hypertension
– pre operative hypervolemia ( particularly in patients with delayed graft function (DGF) ) – induction immunosuppression (Since a steroid dose of more than 20 mg of prednisone per day is the threshold for having HTN , high-dose IV steroids can contribute to HTN during immediate post-transplant period ) – inadequate pain control ( Opioid analgesic is commonly used for pain management during immediate post-transplant period ) – rebound hypertension ( Beta-adrenergic agonists, clonidine (both oral and transdermal forms) , and beta-blockers are commonly associated with this phenomenon, particularly when abruptly stopped )
2- early post transplant hypertension
Defined as the time between 24 and 52 weeks post-transplantation
-weight gain Obesity (BMI ≥ 30 kg/m2) after kidney transplantation is significantly associated with post-transplant HTN
-CNI , two main mechanisms :
a- altered vascular tone , increased Increased renal sodium transport handling Increased renal sodium transport handling V.C & impaired V.D
b- Increased renal sodium transport handling
>>CNI induces salt-sensitive HTN via activation of the WNK- SPAK-NCC pathway similarly to a rare genetic form of HTN , called familial hyperkalemic hypertension (FHHt, also called Gordon syndrome or pseudohypoaldosteronism type 2 , manifests as hyperkalemic hypertension with a non-anion gap metabolic acidosis and hypercalciuria
>>CNI inhibits calcineurin and leads to phosphorylation and activation of WNK and SPAK kinases and NCC. Therefore, sodium and chloride reabsorption in the DCT is increased and salt-sensitive HTN occurs. Low fractional excretion of chloride supports increased NCC activity , and a decreased plasma aldosterone level is consistent with volume expansion. So , theoretically , thiazide diuretics should be effective for CNI-induced HTN .
-maintenance steroid use
–Hypertensive Donor Kidney (study in kidney transplant recipients who had undergone native nephrectomy before transplantation from normotensive donors found that all recipients were normotensive post-transplant without need for antihypertensive therapy )
– Transplant Renal Artery Stenosis (TRAS)
>>Approximately 1–5% of post-transplant HTN is secondary to TRAS , may occur at any time after kidney transplantation but is generally diagnosed between 3 and 24 months post transplantation
>>causes : immunologicakl & non immunological factors
>>clinically :uncontrolled HTN , flash pulmonary edema , increased of s.cr after ACEI & ARBS
>>diagnosis: US doppler , CT angiography , MRA
>>management : -Patients with worsening serum creatinine and/or uncontrolled HTN attributable to TRAS should undergo renal artery angioplasty with stenting
-Surgical revascularization is reserved for cases of unsuccessful angioplasty.
3- Late Post-transplant Period :
– Chronic Renal Allograft Dysfunction
– Fibroblast Growth Factor (FGF) 23
- Obstructive Sleep Apnea
>> risk factors for OSA in kidney transplant recipients are male gender, obesity, use of hypnotic drugs, presence of severe comorbidity (e.g., heart disease, cerebrovascular disease, peripheral vascular disease, diabetes mellitus), and impaired kidney function
>> appropriate management of OSA is an essential component of the antihypertensive therapy in kidney transplant recipients who later develop renal allograft dysfunction especially with resistant HTN
OUTCOMES :
Increased post-transplant SBP and DBP were associated with progressively decreased renal allograft function and death-censored chronic graft failure
BLOOD PRESSURE MEASUREMENT :
-office blood pressure (OBP)
– home blood pressure monitoring (HBPM) , recording at least twice the daily average of two home blood pressure readings over a minimum of 4 days
– 24- h ambulatory blood pressure monitoring (24-h ABPM), which requires wearing an electronic blood pressure measurement device to record and averages multiple readings over a 24 h period
MANAGEMENT :
–Non-pharmacologic : such as diet, exercise, and stress reduction for all patients.
• Beta-blockers (have cardioprotective effects and survival benefit , decrease proinflammatory cytokines, which are known to increase the risk for atherosclerosis , s/e >>hyperkalemia , proteinuria & masking hypoglycemia symptoms )
• Renin-Angiotensin Aldosterone System blockade – Angiotensin-converting enzyme inhibitors – ARB, angiotensin II receptor blockers – Mineralocorticoid receptor antagonists
>>avoid in early period post transpalnt
• Alpha1 antagonists( djunctive therapy)
• Alpha2 agonists (>>Centrally acting , work on presynaptic alpha2 adrenoceptors in the central nervous system and suppress central sympathetic activity
· clonidine>> associated with weight gain and progressive resistance with continued use.
>> rebound HTN is common after discontinuation of clonidine, and patients who are on clonidine prior to kidney transplant tend to have uncontrolled HTN resulting from this rebound phenomenon. In these patients, clonidine is often re-started and be tapered off during early post-transplant period
· methyl dopa>> associated with antihypertensive tolerance, edema, and weight gain
· Procedural or surgical interventions Specific treatment modalities :
– HTN is a very common disease in CKD and ESRD and remains so after kidney transplantation. The pathogenesis of post-transplant HTN is complex. BP measurement is still the main barrier to accurately diagnose and follow-up in HTN management. A 24-h ABPM, though the gold standard, is inconvenient and not wildly utilized.
-The choice of antihypertensive medication requires the clinician to take transplant and immunological factors into the consideration. Management for OSA and interventions for resistant HTN, such as transplant renal artery angioplasty ± stenting, bilateral native nephrectomy, and native RDN, remain options for resistant HTN in selected kidney transplant recipients.
Summary of the article:
-Hypertension is one of the most common cardiovascular morbidities.
Causes can be classified according to the onset either immediately post-transplant, early or late.
-Immediately after the transplant may be due to induction IS drugs, rebound hypertension, hypervolemia or inadequate pain control.
-Early onset may be due to steroids, renal artery stenosis or CNI’s.
-Late onset may be due to chronic allograft dysfunction or failing native kidneys.
Antihypertensive medications used:
-Calcium channel blockers (dihydropyridine or non-dihydropyredine)
-B-blockers
-alpha 1 blocker
-Diuretics
-ACEI or ARBS
Management of post-transplant hypertension in my center
-The treatment of immediate post-transplant hypertension is done through nitroglycerin infusion, CCBs (dihydropyridine based-amlodipine), B blockers and diuretics in cases of hypervolemia/pulmonary congestion or edema.
-The Use of non dihydropyredine in cases associated with low drug levels.
-Alfa blockers are used in cases of associated with prostatic enlargement or as add on drug.
-ACEI or ARBs in cases associated with proteinuria (diabetic nephropathy or on mTori or those with chronic allograft nephropathy with acceptable eGFR).
Hypertension is one of the most common comorbid among renal transplant recipient especially those with history of diabetes mellitus, hyperlipidemia, and obesity.
The pathogenesis of post-transplant hypertension is complex and is multifactorial. Post-transplant hypertension can be divided into immediate, early, and late post-transplant periods.
Volume overload from intravenous fluid administration is common during the immediate post-transplant period and commonly contributes to hypertension seen early after transplantation.
Immunosuppressive medications and donor kidneys are associated with post-transplant hypertension occurring at any time point after transplantation.
Transplant renal artery stenosis and obstructive sleep apnea (OSA) are recognized causes of resistant hypertension post-transplantation.
Blood pressure (BP) targets and management involve both non-pharmacologic and pharmacologic treatment ; preferably CCB , betablocker, diuretic avoid ACE/ ARB. and should be individualized. BP of <130/80 mmHg is a reasonable target. Similar to complete renal denervation in non-transplant patients, bilateral native nephrectomy s another treatment option for resistant post-transplant hypertension.
Further research needed for evidence for the pathogenesis of post-transplant HTN and guide clinicians on the appropriate BP measurement method, use of antihypertensive medications, surgical or procedural interventions, and establish BP targets for kidney transplant recipients.
Kidney transplantation is the treatment of choice for advanced chronic kidney disease unless contraindicated .Cardiovascular morbidity and mortality remain high after transplantation. Major and important risk factor for CVD is Hypertension- one of the leading cause of CKD and accounts for about 24-90% post transplantation. Also associated with metabolic diseases, such as diabetes mellitus, hyperlipidemia, and obesity. Hypertension can be classified into persistent , Recovered hypertension ,persistent normotensive and Post transplant Hypertension. Target blood pressure should be <130/90mmHg in kidney transplant patients according to ACC/AHA guidelines. Post transplant hypertension is defined as elevated BP persistently with the use of antihypertensive medications after kidney transplantation. Post transplant hypertension can further be categorized based on time of presentation.
1) Immediate post transplantation can be because of Hypervolemia during the surgery, heavy doses of steroids,Rebound Hypertension and Inappropriate Pain Management
2) Early post-transplant hypertension can be due to drugs(CNIs, steroids)and TRAS.
3) Late post-transplant-due to Chronic Renal Allograft Dysfunction,Fibroblast Growth Factor (FGF) 23 and Obstructive Sleep Apnea
BLOOD PRESSURE MANAGEMENT OF POST RENAL TRANSPLANT PATIENT.
Non-pharmacologic interventions are similar to other types of patients –adopt lifestyle changes like modification in diet, exercise at least five times a week , and stress reduction, and smoking cessation.
Pharmacological management of post renal transplant hypertension
1) Diuretics-loop diuretic( In case of volume overload with peripheral edema and pulmonary congestion)
Thiazide diuretic (CNIs salt sensitivity hypertension ),Mineralocorticoid receptor antagonist (anti-proteinuric effect and cardiovascular benefits )
2) Beta blocker-most common anti-hypertensive drugs-reduce sympathetic effect and decrease pro-inflammatory cytokines but cause masking of hypoglycemic symptoms
3) Calcium channel blocker- a preferred first line antihypertensive agent for kidney transplant recipients if no contraindication -act as a vasodilator to counter the vasoconstrictive effect of CNIs and prevent post-transplant acute tubular injury (ATI) or DGF.
4) ACEIs and ARBs-not to be used in early post transplant period as chances of hyperkalemia and worsening of graft function.it has additional effect in reducing proteinuria and cardiovascular benefit.
5) Alfa 1 antagonist-to be used along with other anti-hypertensives , not a potent drug.
6) Alpha 2 agonist-major side effect is rebound hypertension when abruptly stopped.
Surgical Management: in cases of resistant and refractory hypertension .Native nephrectomy ,Native renal sympathetic denervation, Catheter ablative sympathetic denervation
How do you manage hypertension after kidney transplantation in your workplace?
Non-pharmacological management at our center is almost the same ,however pharmacological treatment includes-first line calcium channel blocker(amlodipine) followed by beta blocker (bisoprolol or labetolol),then alpha blocker or vasodilator like hydralazine .Loop diuretic are only given in cases of volume overload.In cases of hypertensive emergency-first line is labetolol and with angina symptoms nitrates.
Post kidney transplant hypertension is a common medical problem ,it divided into three groups according to the time of diagnosis ;immediate ,early and late
the main cause of immediate is fluid overload and pretransplant hypertension
the early group risk factors had relation with drugs like CNI and predinsilone,the late presentation represents chronic allograft failure or renal artery stenosis
so the diagnosis could be office measurement or ambulatory 24 hr measurement
Mangment start by life style modifications,diet control and then pharmacological treatment,drugs used in mangment are calcium Chanel blockers,dirutics ,beta blockers
in our center we used same way of treatment
Kidney transplant is best mode of RRT, it improves survival & quality of life.
With calcineurin inhibitors (CNI) in the 1980’s short-term renal allograft survival has greatly improved
Several immunological and non-immunological causes contribute to long-term renal and patient survival outcomes.
Similar to non-transplant patients, cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality in kidney transplant recipients (4). Hypertension (HTN) is a usual finding in this population and one of the most common risk factors for CVD (5).
review the pathogenesis of posttransplant HTN,
including transplant renal artery stenosis (TRAS)
and differing management options based on the etiology of hypertension in different clinical transplant recipient scenarios.
Determining when non-pharmacological interventions, including transplant renal artery angioplasty and/or stenting, bilateral native nephrectomy, and native renal denervation (RDN), are appropriate will also be discussed.
EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION
The greater incidence of post-transplant hypertension maybe related to the introduction of cyclosporine
A study in Spain looked at patients transplanted in three different years (1990 vs. 1994 vs. 1998) and noted a progressive increase in the incidence of post-transplant HTN with subsequent years for all those three periods. The number of antihypertensive medications required in more recent transplants also increased compared to patients who were transplanted earlier (9).
Overall prevalence of post-transplant HTN has ranged from 24 to 90%
DEFINITION OF POST-TRANSPLANT HYPERTENSION
Post-kidney transplant HTN can be defined as a
1. persistently elevated BP or
2. normotension with use of antihypertensive medications after successful kidney transplantation
posttransplant HTN with different cutoff levels are reported as 140/90 or 145/95 or 150 /90 in different studies
In addition to the defining normal BP levels, the presence or absence of HTN during the pre-kidney transplant period may further categorize kidney transplant recipients into four groups:
1. persistent HTN, occurs in patients with HTN both in the pre- and posttransplant periods. Incidences 40%
2. recovered HTN, have HTN only during the pre- but not the post-transplant period. Incidences 28%.
3. persistent normotension, patients have no history of HTN preceding transplant and remain normotensive post-transplant. Incidences 13%.
4. post-transplant HTN. develops de novo HTN after kidney transplant incidences 19%.
In this review, post-kidney transplant HTN refers to persistent and post-transplant (de novo) HTN unless otherwise specified.
The European Society of Hypertension and the European Society of Cardiology guidelines defined isolated Systolic HTN in the general population as SBP ≥140 and DBP <90 mmHg (20). Similar to elderlies
Pathogenesis of isolated systolic HTN involves in both intrinsic alterations resulting from
1-normal aging process
2-development of modifiable risk factors leading to increased arterial stiffness .
Diastolic HTN is defined as DBP of ≥90 mmHg, with a SBP 130 or DBP >80 mmHg .
A recent 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a target BP of <130/80 mmHg. More than this will be defining the hypertensive post kidney transplant.
PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION
Identifying initial occurrence of post-transplant HTN can narrow the differential diagnosis for the etiology and can tailored therapy.
1-Immediate Post-transplant Period
During this time, post-transplant HTN is generally a result of external factors like transplant surgery, IV fluids, and high doses of steroids.
Peri-transplant Hypervolemia
IV fluid given during surgery and in the immediate postoperative period can lead to hypervolemia, particularly in patients with delayed graft function (DGF). A single center cross-sectional study showed that the prevalence of hypervolemia measured by multifrequency bioimpedance analysis for extracellular fluid in stable kidney transplant recipients was 30%, and up to 5% had severe hypervolemia. This study showed that hypervolemia was significantly associated with elevated systolic, diastolic, and mean arterial pressures.
Several indicators can be used to estimate volume status.
These include
· conventional measurements such as BP, heart rate, urine output, central venous pressure, and pulmonary artery pressure.
· non–conventional measurements such as intraoperative transesophageal echocardiography , non-invasive dynamic cardiac output technology, e.g., pulse contour analysis, pulse wave transit time, thoracic electrical bioimpedance/bioreactance, and carbon dioxide rebreathing technologies. These are not readily available.
High-Dose Steroids
· Causing alterations in intrinsic pressor response leading to arterial vascular resistance
· Might be responsible for HTN during immediate post-transplant period.
Rebound Hypertension
Medications Such as B blockers and clonidine.
Inappropriate Pain Management
2-Early Post-transplant Period
systolic HTN (≥140 mmHg) occurred at the mean duration of 26–50 weeks after kidney transplantation, while the baseline renal allograft function and stable dose of maintenance immunosuppressive medications are generally reached around 3–6 months post-transplant.
Weight Gain
Between 6- and 12-months post-transplantation, weight gain commonly occurs, Obesity (BMI ≥ 30 kg/m2) after kidney transplantation is significantly associated with post-transplant HTN
Positive fluid intake from intra-and post-operative IV fluid is a common cause of weight gain, However, after regaining renal allograft function, urinary excretion of the fluid gain can mobilize sodium and water. This can partly help to control BP.
Calcineurin Inhibitors
There are two main mechanism of CNI-induced post-transplant HTN resulting from interfering vascular tone and renal sodium transport handling.
· Renal vasoconstriction. mediated by endothelin rather than angiotensin 2.
· Renal vasodilation. Impaired vasodilation is a result of CNI induced reduction of nitric oxide, a vasodilator. CNIs inhibit inducible nitric oxide synthase in vascular smooth muscle cells
· Increased renal sodium transport handling
Steroids
Hypertensive Donor Kidney
Transplant Renal Artery Stenosis (TRAS)
3-Late Post-transplant Period
Chronic Renal Allograft Dysfunction
Fibroblast Growth Factor (FGF) 23
Obstructive Sleep Apnea
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
Cardiovascular Outcomes-Related to Post-transplant Hypertension, During the post-transplant period, elevated BP is associated with poorer renal allograft and patient outcomes.
HTN is one of the most important risk factors for heart failure, particularly heart failure with preserved ejection fraction (HFpEF). Uncontrolled HTN after kidney transplantation leads to structural damage to both the renal allograft and heart eventually resulting in decreased renal and cardiac functions.
BLOOD PRESSURE MANAGEMENT
pharmacological and non pharmacological
Others include native nephrectomy
Native Sympathetic denervation and Catheter Ablative Renal Denervation
in our practice
we exclude dehydration or over hydration , then we initiate anti-hypertensives including ACE and calcium channel blockers
Definition of hypertension after kidney transplantation is still controverse , while ACC/AHA define HPN in general non transplantation population as systole >130 and diastole>80 mmhg and defind isolated systolic HPN as systole > 140 while diastole <90 which is common in elderly population mainly due to arterial stiffness while isolated diastolic HPN refers to diastole > 90 mmHg while systole is <140 that is more common in young ,obese patients with sedentary life , but in transplant population no definite cut off levelto define HPN but most investigators consider level >130/80 mmHg as HPN .
Posttransplantation HPN can be classified according to either
A) onset time : it can be classified into
1) immediate onset : usually caused by volume overload, effect of induction IS , in adequate pain control, rebound HPN of the pre transplant HPN
2) early onset : wt gain , drug effect specially steroid and CNI .
3) late onset : usually it’s drug induced transplant nephropathy, transplant renal artery stenosis, increase fibroblast growth factor 23 , sympathetic over activity and native kidneys induced HPN or other causes.
B) According to HPN status before transplantion, post transplantion HPN can be further devided into
1) Persistent HPN:
refers to HPN that excite pre and post transplant
2) recoverd HPN :
HPN present pre but not post transplant
3) persistent norm tension :
no HPN , neither pre nor post transplant
4) post transplant HPN :
dono vo HPN that start after transplantion and was not present pre transplant.
Drug effect specially steroid and CNI , Hypertensive donor , transplant artery stenosis
Transplant renal artery stenosis (TRAS)
is a common vascular complications in kidney transplantion affecting 1-23% of patients and is responsible for upto 5% of cases of post transplant HPN. It’s caused by interaction between immunological and non immunological causes
2- Non immunological causes : vascular injury during transplant operation, presence of vascular disease in donor or recipient, atherosclerosis, CMV infection.
2- Immunological causes as
Immune complex mediated endothelial injury
Clinical presentation of TRAS :
– unexplained deterioration of kidney function.
– generalized odema due to renal ischemia that activate RAS system
Investigations
1- duppler US on renal vessels : non invasive, can diagnose presence and severity of TRAS , but it’s operator dependant
2- Renal artery CT : risk of contrast nephropathy is present.
3- MRA.
4- Carbon dioxide (CO2) angiography.
Treatment of TRAS
1- pharmacological treatment: ACEI or ARBS + diuretics
2- Renal artery angioplasty and stent insertion.
3- surgical revascularization.
Out come of HPN after kidney transplantation
pre transplant HPN can affect patient and graft survival where lower diastolic BP is associated with better survival.
Post transplant HPN inversely affect graft and patient survival and increase associated CV risk
Management of post transplantion HPN
1- non pharmacological measures ,: stop smoking , regular exercise, low salt diet .
2- Drug therapy including CCB , BB and diuretics
Treatment of refractory post transplant HPN
1- Native nephrectomy
2- Bilateral renal sympathetic denervation .
B) Treatment of HPN in kidney recipient n my institution
1- In mild HPN :
-During early post operative period :
Revise volume status , adequate pain control , psychological support and sometime we had to use low dose anyxolytic drugs.
-After longer time from transplantation
We start with revising patient diet specially salt intake, volume status and smoking and life style modification . If no improvement or HPN progressed to higher level ,we consider drug therapy starting with CaCB, BB and centrally acting drugs
Epidemiology of post transplant hypertension
Prevelance is 24 to 90%.
Definition of post transplant HTN
Post transplant HTN is a persistent elevation of BP or normotension with use of antihypertensive medications after successful kidneytransplantation.
Post transplant HTN is persistent HTN or denovo post transplant HTN.
SBP > 140, DBP > 90 mmHg.
Pathogenesis of post transplant hypertension
1. Immediate post transplant period
Peri transplant hypervolemia
Induction immunosuppressive medications ( high dose steroids)
Rebound hypertension due to abrupt discontinuation of antihypertensive therapy in pre transplant BP medications to avoid early hypotension especially B blockers or clonidine.
Inadequate pain control.
2. Early post transplant
Weight gain
Calcineurin inhibitors
Steroids
Hypertensive donor kidney
Transplant renal artery stenosis
3. Late post transplant
Chronic renal allograft dysfunction
Obstructive sleep apnea
Fibroblast growth factor 23
Failed native nephrectomy
Sympathetic overactivity
Outcomes of HTN after kidney transplantation
Elevated BP is associated with poorer renal allograft and patient Outcomes.
HTN is one of the most important risk factors for heart failure,
especially heart failure with preserved ejection fraction.
Patients with LVH or HFpEF have increased morbidity and mortality and are at high risk for cardiac related events.
BP measurement
A 24 hours ABPM though the gold standard, is inconvenient and not widely utilized.
Home blood pressure monitoring
Office blood pressure recording
Blood pressure management
1. Lifestyle modifications as diet, exercise and stress reduction are required for all patients.
2. Pharmacological therapy
Choice of medications depending on patient’s characteristics, tolerability and medication side effects ( diuretics, CCB,BB, Renin angiotensin aldosterone system blockade , Alpha1 antagonists or Alpha 2 agonists).
3. Procedural or surgical interventions
Transplant renal artery stenosis: Transplant renal artery angioplasty +/- stenting.
Obstructive sleep apnea: CPAP
Failed native nephrectomy: bilateral native nephrectomy
Sympathetic overactivity: native renal denervation
This is a review of post-transplant hypertension epidemiology, pathogenesis, specific etiologies. cardiovascular and survival outcomes, medications, guidelines and non-pharmacological interventions
DEFINITION OF POST-TRANSPLANT HYPERTENSION:
Is a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation. the cut values are less than 140/90 in most of studies.
It is classified according to presence or absence of HTN during the pre-kidney transplant period into four groups: persistent HTN, recovered HTN, persistent normotension, and post-transplant HTN.
1- Persistent HTN occurs in patients with HTN both in the pre- and posttransplant periods,
2- recovered HTN have HTN only during the pre- but not the post-transplant period.
3- Persistent normotensive patients have no history of HTN preceding transplant and remain normotensive post-transplant.
4- Post-transplant HTN requires developing de novo HTN after kidney transplant.
Another entity is isolated forms of HTN both systolic and diastolic. The former is the most common phenotype of HTN in elderly patients and the latter occur in younger, sedentary individuals with a higher body mass index (BMI)
PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION:
Post-transplant hypertension can be divided into immediate, early, and late post-transplant periods. Each has different pathogeneses.
1- Immediate :
Peritransplant hypervolemia
Induction medications
Rebound HTN
Inadequate pain control
2- Early:
Weight gain
CNI
Steroid
Hypertensive donor kidney
Transplant renal artery stenosis
3- Late post-transplant
Chronic renal allograft dysfunction
Fibroblast growth factor 23
OSA
Failed native kidney
Sympathetic over activity
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION:
Several studies have demonstrated an association between post-transplant HTN and renal allograft failure. HTN can lead to heart failure with preserved ejection fraction and renal patients has increased tendancy of LVH. kidney transplant recipients with either of these have increased morbidity and mortality and are at high risk for cardiac-related events. Uncontrolled HTN after kidney transplantation leads to structural damage to both the renal allograft and heart eventually resulting in decreased renal and cardiac functions.
BLOOD PRESSURE MEASUREMENT
Reliable BP measurement can be standardized with the following definitions:
-office blood pressure :the mean of three non-invasive BP measurements is referred to as
-home blood pressure monitoring :recording at least twice the daily average of two home blood pressure readings over a minimum of 4 days
-24h ambulatory blood pressure monitoring : requires wearing an electronic blood pressure measurement device to record and averages multiple readings over a 24h period
BLOOD PRESSURE MANAGEMENT
1- Lifestyle modifications: Diet, Exercise and Stress reduction
2- Pharmacological therapy: Diuretics , Calcium channel blockers, Beta-blockers, RAS blockade , Alpha1-antagonists and alpha2 agonists
3- Procedural or surgical interventions: Transplant renal artery angioplasty ± stenting , Continuous positive airway pressure , Bilateral native nephrectomy and Native renal denervation
in Sudan, we depend mainly on office blood pressure measuring and we use medications according to international guidelines.
Introduction
Hypertension is one of the most common cardiovascular co-morbidities after successful kidney transplantation. It commonly occurs in patients with other metabolic diseases, such as diabetes mellitus, hyperlipidemia, and obesity. The pathogenesis of post-transplant hypertension is complex and is a result oftheinterplaybetween immunological and non-immunological factors. Post-transplant hypertension can be divided into immediate, early, and late post-transplant periods. This classification can help clinicians determine the etiology and provide the appropriate management for these complex patients. Volume overload from intravenous fluid administration is common during the immediate post-transplant period and commonly contributes to hypertension seen early after transplantation. Immunosuppressive medications and donor kidneys are associated with post-transplant hypertension occurring at any time point after transplantation.
This article will review the pathogenesis of posttransplant HTN, including transplant renal artery stenosis (TRAS) and diering management options based on the etiology of hypertension in dierent clinical transplant recipient scenarios. Determining when non-pharmacological interventions, including transplant renal artery angioplasty and/or stenting, bilateral native nephrectomy, and native renal denervation (RDN), are appropriate will also be discussed.
EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION
Depending on the definition and methods of blood pressure (BP) measurement utilized, the prevalence of post-transplant HTN has been widely reported, and it has generally increased over time. This greater incidence of post-transplant hypertension maybe related to the introduction of cyclosporine (CsA).A study in Spain looked at patients transplanted in three dierent years (1990 vs. 1994 vs. 1998) and noted a progressive increase in the incidence of post-transplant HTN with subsequent years for all those three periods. The number of antihypertensive medications required in more recent transplants also increased compared to patients who were transplanted earlier . Overall prevalence of post-transplant HTN has ranged from 24 to 90%
DEFINITION OF POST-TRANSPLANT HYPERTENSION
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation. However, the main question that remains is what is a normal BP level? Dierent studies have defined posttransplant HTN with dierent cutolevels for systolic and diastolic blood pressure (SBP and DBP) and dierent requirements for the use of antihypertensive medications.
Isolated forms of HTN both systolic and diastolic still occur after kidney transplantation. The European Society of Hypertension and the European Society of Cardiology guidelines defined isolated systolic HTN in the general population as SBP 140 and DBP <90 mmHg (20). This is the most common phenotype of HTN in elderly patients
PATHOGENESISOFPOST-TRANSPLANT HYPERTENSION
-Immediate Post-transplant Period
During this time, post-transplant HTN is generally a result of external factors like transplant surgery, IV fluids, and high doses of steroids.
1-Peri-transplant Hypervolemia
2-High-Dose Steroids
3-Rebound Hypertension
4-Inappropriate Pain Management
–Early Post-transplant Period
1-Weight Gain
2-Calcineurin Inhibitors
3-Steroids
4-Hypertensive Donor Kidney
5-Transplant Renal Artery Stenosis (TRAS)
–Late Post-transplant Period
Apart from the above-discussed factors contributing to HTN in the early post-transplant period, some factors may contribute to HTN in the late post-transplant period.
1-Chronic Renal Allograft Dysfunction
2-Fibroblast Growth Factor (FGF) 23
3-Obstructive Sleep Apnea
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
Pre-transplant BP is associated with renal allograft and patient survival outcomes after kidney transplantation. Very low pretransplant SBP (<110 mmHg) and DBP (<50 mmHg) are associated with a decrease in renal allograft loss. Specifically during dialysis lower pre- and post-dialysis DBP are associated with better patient survival post-transplantation
Cardiovascular Outcomes-Related to Post-transplant Hypertension
HTN is one of the most important risk factors for heart failure, particularly heart failure with preserved ejection fraction (HFpEF) (124). Kidney transplant recipients with left ventricular hypertrophy (LVH) or HFpEF have increased morbidity and mortality and are at high risk for cardiac-related events. Both pressure and volume overload contributed to LVH, which is further exacerbated by age, genetic factors, vascular hemodialysis access, dialysis vintage, diabetes, and blood pressure
BLOOD PRESSURE GUIDELINE FOR KIDNEY TRANSPLANT RECIPIENTS
BP targets have been a controversial topic not only in the nontransplant population but also in kidney transplant recipients. Several professional societies from different countries have created clinical practice guidelines with some similaritiesand differences . Until there is strong clinical outcome evidence in terms
of CV, patients, or renal allograft survival, BP targets should be individualized, taking into account immunologic and nonimmunologic factors that are contributing to HTN in each kidney transplant recipient.
CONCLUSIONS
HTN is a very common disease inCKD and ESRD and remains so after kidney transplantation. The pathogenesis ofpost-transplant HTN is complex. BP measurement is still the main barrier to accurately diagnose and follow-up in HTN management. A 24-h ABPM, though the gold standard, is inconvenient and not wildly utilized. The choice of antihypertensive medication requires the clinician to take transplant and immunological factors into the consideration. Management for OSA and interventions for resistant HTN, such as transplant renal artery angioplasty ± stenting, bilateral native nephrectomy, and native RDN, remain options for resistant HTN in selected kidney transplant recipients. There is no conclusive BP target for this population and therapy targets need to be individualized. Further research to develop a stronger body of evidence for the pathogenesis of post-transplant HTN and guide clinicians on the appropriate BP measurement method, use of antihypertensive medications, surgical or procedural interventions, and establish BP targets for kidney transplant recipients.
In our center
1-focus on modification of life styles
2-encourage for daily exercise
3-decease steroid dose if possible
4-if no benefits we use the pharmacological methods
Hypertension is one of the major factor causing cardiovascular co-morbidities.
It is common that hypertension persists even following kidney transplantation in immediate and late post transplant period. Its prevalence has increased after the beginning of use of calcineurin inhibitors.
Post kidney transplant hypertension is divided into three main groups depending on the onset of hypertension ;immediate, early and late.
There are no consensus guidelines for defining post transplant hypertension but there are studies which have tried defining post transplant hypertension. Their range varies from SBP > 140-150 and DBP > 90-95 mm Hg.
Post transplant hypertension has also been classified further in 4 groups depending on presence or absence of pre transplant hypertension :persistent hypertension ,recovered hypertension ,persistent normal Bp, and post-transplant hypertension.
-Immediate post transplantation – hypervolemia, induction immunosuppression, rebound hypertension and inadequate pain control-
Early post transplantation – weight gain, CNI, steroids, hypertensive donor kidney and TRAS
-Late post transplantation – Chronic allograft dysfunction, FGF23, OSA, failed native kidneys and sympathetic overdrive.
The higher is the post transplant hypertension, the higher the chance of renal allograft failure. BPs as low as SBP<110 and DBP< 50 are associated with decreased renal allograft lost.
HTN management includes lifestyle modification, pharmacological therapy and surgical interventions ;native nephrectomy and renal sympathetic denervation.
This article explains post transplant hypertension in satisfactory depth and could be very informative and practical..
1-Briefly summarise this article
Approach and Management of Hypertension After Kidney Transplantation
EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION
The prevalence of post-transplant HTN has been widely recorded and, depending on the criteria and techniques of blood pressure (BP) measurement used, it has generally risen over time. The introduction of cyclosporine (CsA) may have contributed to the higher frequency of post-transplant hypertension. From 24 to 90% of people had post-transplant HTN overall.
DEFINITION OF POST-TRANSPLANT HYPERTENSION
after kidney replacement After a successful kidney transplant, HTN is characterized by persistently increased blood pressure or normotension with antihypertensive drug use.
In addition to defining normal blood pressure levels, the presence or absence of HTN in the time before a kidney transplant may further divide kidney transplant recipients into four groups: post-transplant HTN, persistent HTN, recovered HTN, and persistent normotension.
Patients with persistent HTN experience HTN both before and after transplantation, whereas those with recovered HTN only experience HTN before transplantation and not after. Patients with persistent normotension have no history of HTN before transplant and continue to have normal blood pressure after transplant. After a kidney transplant, de novo HTN must occur in order to have post-transplant HTN.
After a kidney transplant, isolated forms of HTN, both systolic and diastolic, continue to exist.
A suitable definition of HTN in post-transplant recipients may be BP 130/80 mmHg.
PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION
common factors contributing to post-transplant hypertension during three different periods.
Immediate Post-transplant Period
Early Post-transplant Period
Late Post-transplant Period
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION :
Pre-transplant blood pressure is linked to renal allograft and post-kidney transplant patient survival rates. Renal allograft loss is decreased by very low SBP (110 mmHg) and DBP (50 mmHg) levels prior to transplant. Lower pre- and post-dialysis DBP, in particular, is linked to improved patient survival after transplantation .
Elevated blood pressure is linked to worse renal allograft and patient outcomes in the post-transplant period. However, as was already mentioned, there are a number of renal allograft injuries that are linked to post-transplant HTN.
Cardiovascular Outcomes-Related to Post-transplant Hypertension:
One of the main risk factors for heart failure, especially heart failure with preserved ejection fraction (HFpEF), is high blood pressure (HTN) .Patients undergoing kidney transplantation who have LVH or HFpEF have a higher risk of morbidity and death as well as cardiac-related complications. Both pressure and volume overload played a role in LVH, which was made worse by age, genetics, vascular hemodialysis access, dialysis vintage, blood pressure, diabetes, and other conditions.
BLOOD PRESSURE MANAGEMENT
Non-pharmacological measures :
Non-pharmacologic interventions, such as diet, exercise, and stress reduction, should always be part of treatment of HTN.
Pharmacological measures:
Use of Antihypertensive Medications
Diuretics, Loop Diuretics, Thiazides,
Mineralocorticoid Receptor Antagonists
Beta-Blockers
Calcium Channel Blockers
Angiotensin-Converting Enzyme Inhibitors
(ACEI) and Angiotensin II Receptor
Blockers (ARB)
Alpha1-Antagonists
Alpha2 Agonists
OTHER MANAGEMENT FOR BLOOD PRESSURE
Native Nephrectomy
Native Renal Sympathetic Denervation
Surgical Renal Denervation by Bilateral
Native Nephrectomy
Catheter Ablative Renal Denervation
2-How do you manage hypertension after kidney transplantation in your workplace?
By changing lifestyle
Non-pharmacological measures and pharmacological measures.
Q1- Introduction:
A very common and complex pathology after the transplantation is Hypertension which can be caused by a lot of nonimmunological and immunological factors that are collateral for transplantation. Transplant renal artery stenosis (TRAS), dyslipidemia, medication effects, in particular, CNI, metabolic syndrome, OSA, obesity, DM can cause high cardiovascular risk and effect the graft survival. Also, post-transplant hypertension, usually associated with chronic graft dysfunction, being classified as early, immediate and late after TX.
The article goes through pathogenesis of hypertension post-transplantation, its causes, classification and the treatment options including interventional angioplasty and pharmacological or native kidney nephrectomy and renal denervation in the type of hypertension which shows resistance, based on the evidence available in the guideline.
Defining post-transplantation:
The meaning and the prevalence Of HTN post-transplantation vary in different studies. However, target Bp has the condition of being less than 130/80 Persistent high blood pressure or normotensive with medications post-transplantation. Other classifications of hypertension include: persistent normotension, persistent HTN, recovered HTN, and post TX HTN, with aging isolated systolic HTN. In addition, common, Post-transplant HTN associated with increased CVS morbidity is in our list.
HTN after the transplantation:
IVF peri-and postoperative time can cause Immediate post-transplant period, leading to induction immunosuppression medications such as steroids accompanied with increased sympathetic over activity, volume overload, deficient pain control also due to sympathetic overactivity, and rebound HTN especially those on BB.
Early post-transplantation: Between 24-52 weeks post-TX, having many factors involved:
immunosuppression therapy (CNI, STEROIDS), Weight gain, hypertensive kidney donor, transplant RAS
CNI Induced HTN:
Change of Vascular tone, with arteriolar vasoconstriction and reduced vasodilator
Late post-transplantation:
OSA, Sympathetic overactivity, Chronic allograft dysfunction, Failed native kidneys, FBGF23, RAS, renal artery stenosis
Q2- Fluid management if overload, calcium channel blockers like dilthiazem and so on.
Hypertension (HTN) is a usual finding in transplant patients and one of the most common risk factors for CVD. After kidney transplantation, the most common cardio-vascular co-morbidities is hypertension.
EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION
This greater incidence of post-transplant hypertension may be related to the introduction of cyclosporine (CsA). Overall prevalence of post-transplant HTN has ranged from 24 to 90%. The number of antihypertensive medications required in more recent transplants also increased compared to patients who were transplanted earlier.
DEFINITION OF POST-TRANSPLANT HYPERTENSION
It is a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation. different studies defined HTN with different cutoff levels for systolic and diastolic blood pressure. In addition to definition of normal blood pressure, the presence or absent of HTN in the pre- and post-transplant period may further categorized in to four categories:
1- Persistent HTN: HTN present in both pre- and post-transplant periods.
2- Recovered HTN: HTN only during pre- but not the post-transplant period.
3- Persistent normotensive patients have no history of HTN before transplant and remain normotensive post-transplant.
4- Post-transplant HTN requires developing de novo HTN after kidney transplant.
HTN is defined isolated systolic HTN in the general population as SBP ≥140 and DBP <90 mmHg.
In elderly patients the systolic BP is usually increased while diastolic BP decrease. The pathogenesis involves both intrinsic alterations resulting from normal aging process accompanied by development of modifiable risk factors leading to increased arterial stiffness. While, diastolic HTN is defined as DBP of ≥90 mmHg, with a SBP <140 mmHg, and is more common in younger, sedentary individuals with a higher body mass index (BMI).
SPRINT demonstrated cardiovascular (CV) benefits of tighter BP control leading to new BP guidelines and re-defined HTN for the general population as systolic blood pressure (SBP) >130 or DBP >80 mmHg. But the definition of HTN in kidney transplant recipients remains controversial.
PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION
There is different pathogenesis in the development of HTN in transplant recipient.
Immediate Post-transplant Period:
HTN in this period is generally a result of external factors like transplant surgery, IV fluids, and high doses of steroids.
A- Immediate post-transplantation
· Peri-transplant hypervolemia
· Induction immunosuppressive medication
· Rebound hypertension
· Inadequate pain control
B- Early post-transplantation
· Weigt gin
· CNI inhibitors
· Steroids
· Hypertensive donor kidney
· Transplant renal artery stenosis
C- Late post-transplantation
· Chronic renal allograft dysfunction
· Fibroblast growth factor 23
· Obstructive sleep apnea
· Failed native kidney
· Sympathetic overactivity.
Calcineurin inhibitors and their role in HTN pathogenesis:
Ø Altered vascular tone
They cause both increase in vasoconstriction and impaired vasodilatation.
Ø Altered renal sodium transport handling:
Sympathetic nervous system activation with subsequent sodium retention.
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
Very low pretransplant SBP (<110 mmHg) and DBP (<50 mmHg) are associated with a decrease in renal allograft loss. In dialysis lower pre- and post-dialysis DBP are associated with better patient survival post-transplantation. During the post-transplant period, elevated BP is associated with poorer renal allograft and patient outcomes.
They found that patients with a SBP >140 mmHg at 1 year who were controlled to a SBP ≤140 mmHg at 3 years post-transplantation had improved renal allograft outcomes and reduced CV death compared to those with persistent SBP of >140 mmHg both at 1 and 3 years post-transplantation.
Cardiovascular Outcomes-Related to Post-transplant Hypertension
Kidney transplant recipients with left ventricular hypertrophy (LVH) or HFpEF have increased morbidity and mortality and are at high risk for cardiac-related events.
Renal insufficiency is involved in the pathogenesis of HFpEF and causes salt-sensitive HTN. Importantly, a
vicious cycle of cardio-renal dysfunction can result from salt and volume overload. Uncontrolled HTN after kidney transplantation leads to structural damage to both the renal allograft and heart eventually resulting in decreased renal and cardiac function.
BLOOD PRESSURE MEASUREMENT
1- Office blood pressure (OBP)
2- Home blood pressure (HBPM) is a common utilized method of following BP
3- 24-h ABPM
There is good correlation between 24-h ABPM and HBPM than between 24-H ABPM and office blood pressure (OBP).
Elevated day and night SBP obtained from 24-h ABPM were associated with declining renal allograft function, and nighttime elevation is stronger association.
24-h ABPM associated more significantly with graft loss, cardiovascular event and death.
Management:
Lifestyle modification regarding diet, exercise, decrease stress.
PHARMACOLOGICAL MANAGEMENTS
Use of Antihypertensive Medications
Study in Poland found that, Beta-blockers were the most common antihypertensive medication used in this cohort followed by calcium channel blockers. Uses of ACEI, diuretics, and alphablockers were about the same. ARB therapy was utilized least.
BLOOD PRESSURE CONTROL DURING PERI-TRANSPLANT PERIOD
Antihypertensive Medications
Volume-overload is a major cause of HTN in CKD and ESRD patients. Volume-dependent HTN is managed with fluid removal during dialysis. Recipient who are about to undergo the transplant surgery are usually left with post-dialysis weight slightly above their established dry weight in an effort to avoid intra- and post-operative hypotension.
ACEI and ARB are generally held following a transplant. An alpha2 agonist like clonidine, however, may need to be continued during peritransplant period to avoid rebound HTN. Most transplant physician chose the antihypertensive medication according to their local common practice. But antihypertensive drugs should be individualized.
Diuretics
they are not used as first line anti-hypertensive drugs in transplant recipients. As they may cause volume depletion, electrolyte disturbances, and worsening renal allograft function. But they are indicated in special sitting as overload.
Loop Diuretics:
Volume control rather than BP control is the indication for loop diuretics in kidney transplant recipients, especially in peri-operative period. During this period the recipient usually given IV fluid in large volume to keep urine output. Volume overload present with peripheral edema, pulmonary congestion, or HTN, diuretics are used to controlled this condition. loop diuretic use has been associated with increased risk
of UTI during the first 5 years after kidney transplantation, because there use depletes medullary NaCl
gradient, which is known to modulate the adaptive and innate immune response.
Furosemide is the most commonly used loop diuretic. It can be used to predict prognosis in AKI (furosemide stress test FST) in non-transplant patients.
Also, in transplant patient furosemide can provide prognostic value as the inadequate response, < 350 ml within 4 h, to a single IV furosemide dose of 1.5 mg/kg given 3 h after renal allograft anastomosis predict increased risk of DGF. The benefit nd risks of their used should be balanced according to patients need.
Thiazides
They are used commonly in treatment of HTN in general population, but their used in transplant recipients are uncommon due to their metabolic side effects like hyperglycemia, hyperuricemia, hypercalcemia and hyponatremia.
Thiazides inhibit Na-Cl co-transporter, and may control CNI-induced HTN. Calcium channel blockers, due to their vasodilator effect, are commonly used antihypertensive drugs and are capable of counteract the systemic and renal vasoconstrictive effect of CNI via endothelin. But due to their side effects like peripheral edema and proterinuria, the thiazide are suitable alternative to them for BP control in these cases.
Also, thiazides are good in transplant recipient with hypomagnesemia, especially loop diuretic can worsen it as they can cause magnesium wasting.
CNI and loop diuretics act through the same pathway causing hypomagnesemia, so their combination can cause further urinary magnesium loss.
Thiazides, on the other hand, increase s. Mg when used with CNI. Although, long-term thiazide use may lead to Mg wasting when there is concomitant hypokalemia.
Thiazides may be considered for kidney transplant recipients with CNI-induced salt-sensitive HTN and hypomagnesemia.
Mineralocorticoid Receptor Antagonists
They have CV benefits and antiproteinuric effect but are not commonly used in kidney transplant recipients, especially those with impaired renal allograft function. Hyperkalemia is a common side effect that can be worse with CNI-induced hyperkalemia.
One pilot study tests the anti-proteinuric effect of spironolactone, found improvement in the proteinuria by 50%, despite slight decrease in GFR 52 –to-48.
Eplenerone effect on serum potassium had been tested by a study, found slight increase in s. K which was not significant.
Mineralocorticoids are potentially reno-protective by blunting the renal vascular resistance induced by CNI therapy.
With some evidence for antiproteinuric effect and their established safety in transplant recipients even when in combination with ACEI or ARB, MCRA may be a new option for BP control in individual with CNI-induced HTN and proteinuria.
beta-blockers
they have cardio-potective effect and survival advantage in general population, dialysis, and transplant recipients as well. Beta-blocker also have additive effect with ACEI and ARB with greater survival in recipients taking this combination. This action don through its effect on sympathetic nervous system as well, its anti-inflammatory effect by decreasing the cytokines which are atherosclerotic mediators.
Calcium Channel Blockers
The vasodilatory effect of calcium channel blochers can counteract the vasoconstrictive effect of CNIs and improve BP control. They prevent post-transplant acute tubular injury (ATI) or DGF lower ischemic damage in the renal allograft and reduced CNI nephrotoxicity. Although calcium channel blockers provide better renal allograft function, several studies showed no difference in terms of BP control when using verapamil compared to enalapril or doxazosin. Given the available information, calcium channel blockers remain a preferred antihypertensive agent for kidney transplant recipients barring there are no specific indications for other antihypertensive agents or contraindications to calcium channel blocker therapy.
Dihydropyridine calcium channel blockers can compete with CNI for cytochrome P450 (CYP)3A4 isoenzyme, this leads to increase in both calcium channel blocker and CNI exposure levels. Non-dihydropyridine calcium channel blockers inhibit CYP3A4 isoenzyme and significantly increase CNI level.
Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor Blockers (ARB)
ACEIs and ARBs are antihypertensive agents with known antiproteinuric effect. As they decrease GFR at start, it is advisable not use them early post-transplantation to not make confusion regarding graft function. They may be considered in transplant recipients, particularly those with LVH, congestive heart failure, and proteinuria.
Alpha1-Antagonists (doxazosin)
They reduce BP by decreasing peripheral vasoconstriction. But they do not used as first line or as a single drug. Alpha1-antagonist may have a role as an adjunctive therapy rather than first line antihypertensive agent in transplant recipients.
Alpha2 Agonists
They suppress central sympathetic activity. Specifically, activation of alpha2A receptors causes a sympatho-inhibitory effect and lowers BP. They decrease renal vascular resistance. Two of the oldest alpha2 agonists, methyldopa and clonidine, have long been used for BP control. when used as monotherapy, methyldopa is associated with antihypertensive tolerance, edema, and weight gain. Clonidine is also associated with weight gain and progressive resistance with continued use.
Rebound HTN is common after discontinuation of clonidine, and patients who are on clonidine prior to kidney transplant tend to have uncontrolled HTN resulting from this rebound phenomenon. Therefore, clonidine is rarely used as a single antihypertensive agent following kidney transplantation.
OTHER MANAGEMENT FOR BLOOD PRESSURE
Native Nephrectomy
Native Renal Sympathetic Denervation
Surgical Renal Denervation by Bilateral Native Nephrectomy
Catheter Ablative Renal Denervation
calcium channel blocker with or with out Beta-blocker are the fist line therapy in general specially in early period.
Introduction:
Hypertension is common posttransplant. Risk increased in-patient with other risk factors.
Classified as early, immediate and late.
This review the pathogenesis of posttransplant HTN, including transplant renal artery stenosis (TRAS) and differing management options based on the etiology of hypertension.
EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION:
Prevalence and incidence, increased overtime, especially with introduction of CNI.
Prevalence of post-transplant HTN has ranged from 24 to 90%.
DEFINITION OF POST-TRANSPLANT HYPERTENSION:
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation.
The presence or absence of HTN during the pre-kidney transplant period may further categorize kidney transplant recipients into four groups:
Persistent HTN,
Recovered HTN,
Persistent normotension,
Post-transplant HTN.
Different studies have defined posttransplant HTN with different cutoff levels for systolic and diastolic blood pressure;
Budde et al. >150/90 or using antihypertensive medications except the single use of diuretics.
Malek-Hosseini et al. 145/95 or required antihypertensive medication.
Zeier et al. >140/90 mmHg or antihypertensive treatment.
Kasiske et al. ≥140/90 mmHg.
Campistol et al. SBP ≥140 and/or DSP ≥90 and/or treated with antihypertensive medications.
Until there is stronger evidence of an association between BP level and outcomes in kidney transplant recipients, a BP ≥130/80 mmHg may be a reasonable definition for HTN in this population.
PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION:
Immediate Post-transplant Period:
Due to transplant surgery, IV fluids, and high doses of steroids.
Peri-transplant Hypervolemia:
IV fluid given during surgery and in the immediate postoperative period can lead to hypervolemia, particularly in patients with delayed graft function .In addition to CBI ,CAN ,TRAS .FGF23,OSA.
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION:
Poorer renal allograft and patient outcomes.
HTN is one of the most important risk factors for heart failure. Kidney transplant recipients with left ventricular hypertrophy (LVH).
Have increased morbidity and mortality and are at high risk for cardiac-related events.
BLOOD PRESSURE MEASUREMENT:
HBPM in conjunction with OBP for our kidney transplant patients to minimize misclassification of HTN diagnosis, monitor possible white coat or masked HTN, and adjust antihypertensive medications.
BLOOD PRESSURE MANAGEMENT
Non-pharmacologic interventions:
Diet, exercise, and stress reduction.
Pharmacological intervention remains the cornerstone of BP control in this population.
Renal sympathetic denervation:
Of the native kidneys by either bilateral native nephrectomy or catheter, ablation is also treatment option for resistant HTN in this population.
Additionally, other interventions specific to certain etiologies of resistant HTN, such as transplant renal artery angioplasty ± stenting and treatment for OSA, should be implemented.
Guideline for kidney transplant recipients from different scientific medical societies:
KDIGO 2012 (205) ≤130/80.
K/DOQI 2004 (206) ≤130/80
BRA 2011 (209) Clinic blood pressure ≤130/80 125/75 mmHg if urine protein/creatinine ratio (PCR) >50 or ACR>35) (2C) – RAS may be more effective in the minimization of proteinuria but – Used with caution in the first 3 months post-transplant.
CSN Work Group 2014 ≤140/90 regardless of the level of albuminuria ≤130/80 in kidney transplant recipients with Based on comorbidities including DM, stroke, CAD, CCB, recent MI, and CHF – RAS blockers should be avoided in the immediate post-transplantation.
KHA-CARI 2012 guideline (adaptation of the 2009 KDIGO) (212) ≤130/80 in adult – Tighter BP control with BP <125/75 in the patient with proteinuria >1 g/day – Suggests using CCB as the first line antihypertensive agent; however, this should be balance with the patients’ comorbidity and proteinuria. Closely monitor CNI level.
2017 ACC/AHA.
We use CCB in our practice ,late we add ACE or ARB after 3months.
Summarize the article:
Introduction:
Kidney transplantation is still the preferable modality of RRT for CKD patients. CVD is the leading cause of morbidity and mortality post kidney transplantation. HTN is the most common cardio vascular risk factors. It is associated with poor renal allograft and patient outcomes, the overall prevalence in the post-transplant period ranged from 24 to 90%.The pathogenesis is complex and may be related to immunological and non-immunological factors.
Definition and categories of post-transplant hypertension:
Persistently elevated BP ≥130/80 mmHg, or normo-tension with the use of Bp medications after successful kidney transplantation.
Categories:
1. Persistent HTN: both in pre- and post-transplant period (40%)
2. Recovered HTN: only during the pre- and not the post-transplant period (28%)
3. Normo-tension: no HTN pre-transplant, remain normotensive post-transplant(13%)
4. Post-transplant HTN: new HTN after kidney transplant (19%)
Risk factors for post-transplantation hypertension:
In the immediate post-transplant period: Inadequate pain control, Hypervolemia, the use of induction immunosuppression and rebound hypertension.
In the early post-transplant period: weight gain, immunosuppressive medication(steroids and CNIs), TRAS.
In the late post-transplant period: chronic allograft nephropathy, sympathetic over activity, failed native kidneys and FGF-23
Blood pressure management options include:
Non-pharmacologic measures:
life style modification with diet control, encourage exercise, reduce stress.
Pharmacological measures (the cornerstone of BP control):
– Calcium channel blockers: dihydropyridine and non-dihydropyridine can be used. non-dihydropyridine CCBs can increase the CNI levels so careful monitoring of CNIs levels should be done.
– Diuretics: They are not the first line of treatment. Loop diuretics are used in volume overload status but they may worsen renal allograft function and cause electrolyte disturbance. Thiazide diuretics can cause metabolic disturbances and hyperlipidemia. Mineralocorticoid antagonists are used mainly in cases of systolic dysfunction but may result in hyperkalemia.
– Beta-Blockers: have cardiac protection but there use may mask symptoms of hypoglycemia and thyrotoxicosis, worse lipid profiles and also result in hyperkalemia
– ACEI and ARBs: They have anti-proteinuria and cardio-protection effects. Adverse effects are elevated creatinine, hyperkalemia and anemia. Not the drugs of choice during the immediate and early post-transplant periods as the cause irreversible decrease in GFR and confusion with other causes of renal allograft dysfunction.
– Alpha1-Antagonists, Alpha2 Agonists: not first line of treatment
Procedural or surgical interventions:
Conclusion:
· No conclusive BP target and target therapy need to be individualized.
· Further research is needed to develop a stronger body of evidence for the pathogenesis of post-transplant HTN and guide clinicians on the appropriate BP measurement method to achieve BP targets for kidney transplant recipients
How do you manage hypertension after kidney transplantation in your workplace?
· We encourage life style modification.
· With regard to pharmacological measures, we start with dihydropyridine CCBs and beta blockers in the immediate post-transplant period. RAAS inhibitors can be added after the stabilization of graft function
· Procedures and surgery are carried as required. We carry TRAS angioplasty with a good outcome. Native nephrectomy if indicated.
mmaryApproaSuch and Management of Hypertension After Kidney Transplantation Introduction
CVD is a common cause of morbidity and mortality in KTRs. and HTN is the most common risk factor for CVD.
This article will review the pathogenesis of post transplant HTN including Renal Artery Stenosis and different management option based on the etiology of hypertension
Epidemiology of post-Transplant HTN
The greater incidence of post-Transplant HTN may be related to cyclosporine
The overall prevalence of post Transplant HTN from 24-90%
Definition of post-Transplant Hypertension
Post Kidney Transplant HTN can be defined as a persistently elevated BP or normotension with the use of antihypertension medication after KT
The definition of HTN in Kidney Transplant recipients remains controversial and hard outcomes related to BP levels are still limited. Cardiology American guidelines recommended a target BP< 130/80mmHs in post-Renal transplant recipients until there is stronger evidence of an association between BP level and outcome in Kidney Transplant recipients.
Pathogenesis of Post Transplant Hypertension
Immediate post-transplant period:-
During this time, post-Transplant HTN is generally a result of external factors like Transplant surgery, I.V fluid, and high dose of steroid
Peri-Transplant hypervolemia:
I.V fluid during surgery given and post-operative period can lead to hypervolemia and particularly in pts with delayed graft function. The same study showed that hyper volume was associated with elevated systolic, diastolic, and mean artial pressure.
High dose steroid
High-dose IV steroids are the cause of HTN immediately post-Transplant period. And the mechanism is unclear and usually dose of more than 20 mg of prednisolone per day is the threshold for having HTN.
Rebound HTN:-
Discontinuation of anti-hypertensive therapy can lead to rebound hypertension-most probably due to sudden discontinuation of beta blocker , clonidine, and beta-adrenergic against- and this is due to sympathetic overactivity.
Inappropriate pain management:-
Acute pain associated with elevated BP via sympathetic ravens system activation, leading to an increase in peripheral vascular resistance, heart rate, and stroke volume
Early post-Transplant period
Early post-transplant period is the time between 24 and 52 weeks post-transplants
Weight gain
Between 6-12 months post-transplant BMI >= 30kg/m2 after transplant is associated with post Transplant HTN.
Calcineurin inhibitors
The prevalence of HTN in Kidney Transplant recipients is between 70 and 90% two mechanisms of CNI-induced post-transplant HTN:-
1- Interfering vascular tone-
2- Renal sodium Transplant handling steroids
-a systemic review and meta-analysis revealed that steroid avoidance or withdrawal decreases CVS outcomes including HTN but increases the risk of acute rejection.
A randomized control trial demonstrates no difference in blood pressure change between alternative day and daily prednisone.
Hypertensive donor Kidney
Several animal studies revealed a renal rate in the development of HTN Kidney transplantation From Idiopathic hypertension rate donors to genetically normotensive recipients led to post Transplant HTN resulting from deceased renal salt excretion
Transplant Renal Artery Stenosis
TRAS is a common vascular complication that leads to worse renal allograft function and CVS complications.
Including post-transplant HTN 1-5% of post transplant, HTN is secondary to TRAS.
The cause is immunological and nonimmunological causes.
Symptoms and signs of TRAS are non-specific but can be present by unexplained worsening of renal allograft function or uncontrolled HTN.
CDU is the initial imaging study used because it is non-invasive
Peak systolic velocity of main Renal Artery and postenotic intrarenal arterial resistive index. Are used to determine and grade the severity of TRAS.To confirm the diagnosis using CT and MRA Renal Artery.
Therapeutic options for TRAS are pharmacological therapy in addition to renal artery angioplasty with stenting or surgical revascularization.
Use ARB or ACE or diuretics to control the BP.
Angioplasty with stenting if:-
1- Worsening serum creatinine.
2- Uncontrolled HTN due to TRAS.
Late post-Transplant period
Factors that can result in a late post-Transplant period:-
1- Chronic renal allograft dysfunction:–acute and chronic renal allograft injuries both are associated with HTN.
HTN and immunological factors affect the expression of growth factors in Renal allograft and may be the cause of chronic renal allograft dysfunction fibroblast growth factor is
FGF is an independent risk factor of renal allograft loss, CVS, and all causes of mortality in Kidney transplant recipients
High level of FGF is associated with increased SBP and DBP as well as an incident HTN in nonhypertensive yang adults>
Obstructive sleep Apnea:
In one of the studies kidney transplant patients with OSA required a significantly higher number of anti-hypertensive medications and tend to have higher SBP.
OSA is associated with CVS risks, morbidity, and mortality.
The outcome of HTN after kidney transplantation
Pre-transplant BP is associated with renal allograft and patient survival outcomes after kidney transplantation. post renal transplant HTN is associated with poorer renal allograft and patient outcomes .no sufficient data about CVS and mortality outcomes related to isolated diastolic HTN in a kidney transplant recipient and more studies are required to determine appropriate management target for isolated diastolic HTN in this population.
CVS outcomes related to post-transplant HTN:
Kidney transplant recipients with left ventricular hypertrophy or HF PEF have increased mortality and morbidity and also they are at high risk for cardiac-related events
Blood pressure management
Non-pharmacological such as diet, exercise, and stress reduction are crucial in the management.
Pharmacological management
Use of Antihypertensive medication:
Diuretics:
Usually given in the peri-transplant period.
Loop diuretics are usually indicated during the immediate and early post-transplant period.
Thiazides
Uncommon used in kidney transplantation recipients because of their side effects.
Mineralocorticoid Receptor antagonist
Use post-KTRs but can cause hyperkalaemia. some evidence for antiproteinuric effect and safety in transplant recipients even when combined with ACE I or ARBs.
Beta Blocker
Has a cardioprotective effect and survival benefits and also decreases proinflammatory cytokines which increase the risk of atherosclerosis.
Calcium channel blocker
Is an appropriate agent for post-transplant HTN and also can prevent post-transplant acute tubular injury or DGF.
Angiotensin-converting Enzyme inhibitors and angiotensin 2 Receptor Blocker
There was insufficient data regarding the benefit of ACEi or ARBs therapy for the patient or renal allograft survival.
Alpha -Antagonists
Are rarely used as the initial or as a single antihypertensive agent in kidney transplant recipients.
Alpha2-Agonist
Centrally acting alpha-agonist e.g methyldopa, clonidine.
In summary, there is no drug of choice for Bp control after kidney transplantation. Several factors to select the appropriate antihypertensive medication.
The most commonly used medication is calcium channel blocker is the most frequently used combination in post-kidney transplantation.
Other management for blood pressure native nephrectomy
There is evidence that kidney recipient with pre or post transplant native recipient has decreased blood pressure when compared to those without native nephrectomy.
Native renal sympathetic denervation
The effect of RDN on BP control was established, there are surgical or catheter ablation denervation, bilateral native nephrectomy in kidney transplantation is invasive and carries risk so it should be reserved for selected patients
Conclusions
HTN is a very common disease in CKD and ESRD and remains after kidney transplantation.24 hours ABPM is the gold standard measurement. The choice of antihypertensive medication requires the clinician to take a transplant and immunological factor
Consideration, there is no BP target and the therapy target needs to be individualized.
In our centre, we use a calcium channel blocker .and combined it with ACE I or ARBs but we avoid in early transplant period
Approach and Management of Hypertension After Kidney Transplantation
EPIDEMIOLOGY OF POST-TRANSPLANTHYPERTENSION:
Over all prevalence of HT is increasing gradually. May be due to introduction of CNI the prevalence range from 24-90%.
DEFINITION OF POST-TRANSPLANT HYPERTENSION:
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation. Different studies mention different definition of HT, 140/90 or 145/95 or 150/90.
HT post kidney transplantation can categorized into four groups:
1- persistent HTN.
2- recovered HTN.
3- persistent normotension.
4- post-transplant HTN
isolated systolic HTN defined as SBP <140 and DBP <90 mmHg. It is common in elderly patient. diastolic HTN is defined as DBP of < 90 mmHg with a SBP <140 mmHg, is more common in younger,
sedentary individuals.
A recent 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a target BP of <130/80 mmHg.
PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION:
Immediate Post-transplant Period:
a- Peri-transplant Hypervolemia
b- High-Dose Steroids
c- Rebound Hypertension
Early Post-transplant Period:
a- Weight Gain
b- Calcineurin Inhibitors
c- Altered vascular tone
d- Increased renal sodium transport handling
e- Steroids
f- Transplant Renal Artery Stenosis (TRAS)
Late Post-transplant Period:
Chronic Renal Allograft Dysfunction
Fibroblast Growth Factor (FGF) 23
Obstructive Sleep Apnea
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
During the post-transplant period, elevated BP is associated
with poorer renal allograft and patient outcomes.
Opelz et al. conducted a retrospective study conclude that
Increased post-transplant SBP and DBP were associated with progressively decreased renal allograft function and death-censored chronic graft failure.
Cardiovascular Outcomes-Related to Post-transplant
Hypertension:
HTN is one of the most important risk factors for heart
failure, particularly heart failure with preserved ejection fraction (HFpEF).
BLOOD PRESSURE MEASUREMENT:
can be standardized with the following definitions:
– the meanof three non-invasive BP measurements is referred to as office blood pressure (OBP);
– recording at least twice the daily average of two home blood pressure readings over aminimum of 4 days is referred to as home blood pressure monitoring (HBPM),
– 24-h ambulatory blood pressure monitoring (24-h ABPM), which requires wearing an electronic blood pressure measurement device to record and averages multiple readings over a 24 h period .
A 24-h ABPM provides the average of both day and night
BP readings. Physiological decreases in nocturnal BP further
classifies patients into dippers, non-dippers, and reverse dippers.
Lee et al. demonstrated a significant decrease in the nocturnal reduction in SBPafter kidney transplantation.
A 24-h ABPM can address and assist with the common
misclassification of HTN diagnosed traditionally by OBP or
HBPM. Compared with OBP, a 24-h ABPM led to 61% disagreement in diagnosis.
BLOOD PRESSURE MANAGEMENT:
there is no drug of choice for BP control after kidney transplantation. Several factors are involved in selecting the appropriate antihypertensive medications include immunologic and non-immunologic factors as well as the time
after kidney transplantation.
Diuretics:
Diuretics are not commonly used as the first line antihypertensivemedication in kidney transplant recipients
Loop Diuretics:
Volume control rather than BP control is the indication
for loop diuretics in kidney transplant recipients, especially
during immediate and early post-transplant periods
Thiazides:
Thiazide diuretics are commonly used antihypertensives
in general population. They are however uncommon in
the management of kidney transplant recipients because of
their metabolic side effects which include hyperglycemia,
hyperuricemia, hypercalcemia, and hyponatremia
Mineralocorticoid Receptor Antagonists:
Mineralocorticoid receptor antagonists (MCRA) have CV
benefits and antiproteinuric effect but are not
commonly used antihypertensives in kidney transplant
recipients, especially those with impaired renal allograftfunction. Hyperkalemia is a common side effects of MCRA and it may be worse in kidney transplant recipients who have CNI-induced hyperkalemia.
Beta-Blockers:
The cardioprotective effects and survival benefit of beta-blockers make them a favored medication in the general and
ESRD populations . In kidney transplant recipients, a
recent retrospective study from 2001 to 2014 showed that beta blockers are the most common used antihypertensive medication.
Calcium Channel Blockers:
Calcium channel blockers inhibit entry of calcium into vascular
smooth muscle cells, resulting in vascular vasodilation.
Since the vasoconstrictive effect of CNIs leads to post-transplant HTN (172), calcium channel blockers are thought to be an appropriate agent for post-transplant HTN. Theoretically their vasodilatory effect can counteract the vasoconstrictive effect of CNIs and improve BP control.
Angiotensin-Converting Enzyme Inhibitors:
Since proteinuria is a surrogate marker for renal disease, lowering proteinuria is one strategy to slow the progression of CKD. ACEIs and ARBs are antihypertensive agents with known
antiproteinuric effect. ACEIs inhibit angiotensin-converting
enzyme, which converts renin to angiotensin. There was insufficient data regarding the benefits of ACEI or ARB
therapy in terms of patient or renal allograft survival
(ACEI) and Angiotensin II Receptor Blockers (ARB)
Alpha1-Antagonists:
Alpha1-antagonists are rarely used as the initial or as a single
antihypertensive agent in kidney transplant recipients.
OTHER MANAGEMENT FOR BLOOD PRESSURE:
1- Native Nephrectomy.
2- Native Renal Sympathetic Denervation.
3- Surgical Renal Denervation by Bilateral Native Nephrectomy.
4- Catheter Ablative Renal Denervation.
First of all to search for any treatable cause for example volume overload, then to apply the general measure as for any hypertensive patient . than to use medication most commonly used medication involves calcium channel blocker .
The definition of hypertension in kidney transplant recipients is a very controversial topic, but in this work the following was used: as persistently high blood pressure (BP) levels or normotension with the use of antihypertensive drugs after successful kidney transplantation. The importance of hypertension is due to the fact that it is the most common risk factor for cardiovascular diseases, which are the main cause of morbidity and mortality among kidney transplant recipients.
IMPORTANCE OF PRESSURE LEVELS:
Pre-transplant BP is associated with renal allograft and patient survival outcomes after kidney transplantation. Very low pre-transplant SBP (< 110 mmHg) and DBP ( < 500mmHg) are associated with a decrease in renal allograft loss. Specifically during dialysis lower pre- and post-dialysis DBP are associated with better patient survival post-transplantation.
During the post-transplant period, elevated BP is associated with poorer renal allograft and patient outcomes. However, as discussed above, various forms of renal allograft injury are also associated with post-transplant HTN.
CATEGORIZATION:
In general, there are pre- and post-transplant etiologies for the development of post-transplant hypertension, and defining when it first occurred helps to define the differential diagnoses for the etiology of post-transplant hypertension, leading to personalized therapy. The most used categorization divides post-transplant hypertension into: immediate X early X late
Immediate post-transplantation:
– hypervolemia: used in the pre- and perioperative period
– Corticosteroids: effect of immunosuppressive pulse therapy
– Rebound hypertension: due to discontinuation of antihypertensive drugs in the preoperative period;
– acute pain
Early post-transplant
– Weight gain
– Calcineurin inhibitors: altered vascular tone and/or management of sodium transport
– Corticosteroids
– donor kidney with hypertension – sodium retention
– Renal artery stenosis: surgical anastomosis, native vascular disease, fibromuscular dysplasia, vascular rejection
Late post-transplant
– Graft dysfunction
– Fibroblast growth factor
– obstructive sleep apnea
HYPERTENSION MANAGEMENT:
– Non-pharmacological: pain treatment, exercises, diet and stress reduction.
– Pharmacological:
– Diuretics: loop (preferred for volume control) X Thiazides
– Mineralocorticoid receptor antagonists: they are not often used because they induce hyperkalemia, but they have excellent effects for cardiovascular protection and proteinuria decrease
B beta-blockers: they are the most commonly used, they decrease inflammatory cytokines
– ACE inhibitors and ARBs – decreased proteinuria, but no evidence of improved patient or renal allograft survival
– Calcium channel blockers: vasodilator effect that opposes the vasoconstrictor of CNIs. They also prevent acute renal tubular injury.
– Alpha 1 inhibitors – are rarely used, there is no evidence that alpha 1 antagonists provide a superior antihypertensive effect or delay the progression of renal allograft dysfunction
-Alpha 2 inhibitors – central action, inhibiting sympathetic activity.
In summary, there is no drug of choice for controlling BP after kidney transplantation, and the best treatment is the one planned for each patient.
In obvious cases of immediate post-transplant hypertension, we try to induce a decrease in volemide with diuretics and, if that fails, institute hemodialysis. In other situations, we tried to manage drugs, such as decreasing the dose of corticoids and CNI, and introducing antihypertensive drugs.
Post-TX hypertension is classified into:
1- Persistent: Pre-TX HTN that continues Post-TX.
2- Recovered: Pre-TX HTN that disappears Post-TX.
3- Post TX HTN: denovo HTN post-TX.
In RTX: target BP less than 130/90.
Causes of Post-TX HTN:
1- Hypervolemia.
2- High dose of steroids used in induction immunosuppression.
3- Rebound HTN: from reducing or stopping anti-HTN medications.
4- Pain induced.
5- Weight gain.
6- CNI induced.
7- Steroid induced.
8- Transplant renal artery stenosis.
9- Chronic allograft nephropathy.
10- OSA.
11- FGF-23.
Management of Post-TX HTN:
a- Non-pharmacological.
b- Pharmacological:
1- Diuretics especially loop diuretics if fluid overloaded.
2- B-blockers.
3- CCBs: especially in CNI induced HTN.
4- ACE.I/ARBs: postponed to 3 months post TX, useful if DM, HF, proteinuric.
5- Alpha blockers.
6- Alpha-2 agnoists.
7- Native nephrectomy.
8- Native Renal sympathetic denervation.
9- Catheter ablative renal denervation.
Non pharmacological, CCBs, diuretics commonly used in my work place in the early post TX period.
INTRODUCTION
Renal transplantation is the best treatment for advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) of greater survival benefit and achievement of better quality of life. However, still cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in renal transplant recipients affecting their survival. The most common risk factor for CVD is hypertension.
EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION
The incidence of post-transplant hypertension is estimated about 24% ranging to 90% owing to the wide use of cyclosporine (CsA) necessitating the increased number of antihypertensive agents administered to achieve the ultimate control of blood pressure.
DEFINITION OF POST-TRANSPLANT HYPERTENSION
A persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation is the best definition for post-transplant hypertension. In other words, Post-transplant HTN is de novo HTN after kidney transplantation.
Two main points were needed to establish regarding the normal blood pressure value post transplantation and whether hypertension existed pretransplantation or not.
American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a target BP of <130/80 mmHg.
Immediate Post-transplant Period
It is mostly due to some external factors as transplant surgery, IV fluids, and high doses of steroids.
Whereas hypervolemia is evident particularly in patients with delayed graft function (DGF). Weight gain exceeding the pre-transplant dry weight was correlated to immediate post-transplant HTN. BP, heart rate, urine output, central venous pressure, and pulmonary artery pressure are important surrogates to assess the volume status besides the body weight.
High-Dose Steroids may lead to alterations in intrinsic pressor response manifesting arterial vascular resistance.
Rebound Hypertension
Beta-adrenergic agonists, clonidine and beta-blockers are commonly linked to this phenomenon. Sympathetic over activity without renin angiotensin system mediation is the main culprit in the mechanism of rebound HTN from clonidine.
In patients with underlying coronary artery disease (CAD) rebound HTN from beta-blockers causes elevated BP and heart rate, up to serious cardiac events including angina, myocardial infarction, or sudden cardiac death.
Inappropriate Pain Management
Acute pain is causes markedly elevated BP by sympathetic nervous system activation with subsequent increases in peripheral vascular resistance, heart rate, and stroke volume. Also stimulation of the neuroendocrine system via hypothalamic-pituitary adrenal axis aggravates pain-induced HTN.
Early Post-transplant Period
The most contributing factors are:
Weight Gain:
Weight gain is common between 6- and 12-months post-transplantation. Obesity (BMI more than 30 kg/m2) after renal transplantation is significantly causes post-transplant HTN.
Calcineurin Inhibitors
The prevalence of HTN in renal transplant recipients ranges between 70 and 90% compared to pre-CNI era which was estimated by 40 to 50%.
Two main mechanisms lead to CNI-induced post-transplant HTN via interfering vascular tone and renal sodium transport handling. Altered vascular tone in the form of both increased vasoconstriction and impaired vasodilation while CsA results in sympathetic system stimulation with the association of subsequent sodium retention by the effect of phospho-protein synapsin which is found on microvesicles within renal sensory nerve endings. Thiazide diuretics are known to be effective for CNI-induced HTN being of salt sensitive aetiology.
Steroids
The prevalence of HTN decreased in patients taking alternate day steroid therapy. Also despite conflicting data regarding graft survival, steroid withdrawal or avoidance regimens are being adopted recently specifically for those who would be at greater risk for CV outcomes but have immunologically lower risk of rejection.
Hypertensive Donor Kidney
A study conducted in renal transplant recipients who did native nephrectomy prior to renal transplantation from normotensive donors concluded that all recipients became normotensive post-transplant without any need for antihypertensive medications. However, another study in recipients with known familial HTN, renal transplantation from any type of kidney did not affect the prevalence of post-transplant HTN. So there is a proposed role for kidney and genetic kidney disease in developing HTN.
Transplant Renal Artery Stenosis (TRAS)
TRAS may occur at any time post renal transplantation, commonly diagnosed between 3 and 24 months post transplantation. The prevalence of TRAS increased from 2.4 to 12.4% after the introduction of color Doppler ultrasonography (CDU) in 1985, due to improved detection with noninvasive testing.
The pathogenesis of TRAS is complex varying between both non-immunological and immunological contributing factors. The non-immunological factors preclude vascular damage at the time of surgical anastomosis between the donor renal artery and recipient artery as well as the existence of native vascular diseases in both donor and recipient arteries. Also the connection between these smaller arteries might be predisposed to narrowing followed by subsequent development of TRAS. The association between post anastomotic TRAS and de novo class II donor-specific antibodies raises the possibility of immunologic contribution to atherosclerotic TRAS.
The most important common clinical clue that directs to a work-up for TRAS is either unexplained worsening of renal allograft function or uncontrolled HTN. Using imaging studies is preferred notably the CDU being non-invasive, widely available, and relatively inexpensive by assessing the RI to determine and grade the severity of TRAS.
Therapeutic options include pharmacological management alone or adding renal artery angioplasty with stenting or surgical revascularization upon need.
Late Post-transplant Period
The main causes proposed are Chronic Renal Allograft Dysfunction, Fibroblast Growth Factor (FGF) 23, and Obstructive Sleep Apnea.
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
In the post-transplant period, elevated BP is associated with poorer both renal allograft and patient outcomes. Increased post-transplant SBP and DBP were associated with progressively decreased renal allograft function and death-censored chronic graft failure according to Opelz study. Cardiovascular Outcomes-Related to Post-transplant Hypertension are manifested by heart failure with preserved EF.
BLOOD PRESSURE MANAGEMENT
Non-pharmacologic means like healthy diet, exercise, and stress reduction are essential in the management prior to pharmacological treatment. Thiazides can be used in CNI post-transplant HTN being salt sensitive .CCB can be used with monitoring of drug levels. Other lines as diuretics, ACEI or ARBS are discouraged. So antihypertensive agents should be tailored to each patient.
Management of HTN post renal transplantation in our centre is carried out by meticulous identification of the cause, lifestyle modification in the form of healthy diet ,exercise ,cessation of smoking ,perfect fluid balance guided by the patient’s volume status, early detection of rejection, and minimizing steroid doses the sooner the better especially for those with lowest immunological risk. The usage of antihypertensive agents is tailored to every patient individually.
Introduction:
· Cardiovascular diseases are the leading cause of mortality in post-transplant patients, and Hypertension is one of the most common cardiovascular co-morbidities (prevalence ranged from 24 to 90%) it’s important to diagnosed and properly managed.
· Its define as a persistently elevated BP or normotension with use of antihypertensive medications *as SBP ≥140 and DBP <90 mmHg in most of the society guidelines . and divided to 4 types depending on BP status pre transplant: persistent HTN, recovered HTN, persistent normotension, and post-transplant HTN.
Depending on timing to transplantation factors contributed to raise in blood pressure vary:
Immediate Post-Transplant Period:
ü Peri-transplant hypervolemia
ü Induction immunosuppressive medications
ü Rebound hypertension
ü Inadequate pain control
Early Post-Transplant Period: define as between 24 and 52 weeks’ post-transplantation:
ü Weight gain
ü Calcineurin inhibitors
ü Steroids
ü Hypertensive donor kidney
ü Transplant renal artery stenosis
Late Post-Transplant Period:
ü Factors of early post-transplant above
ü Chronic renal allograft dysfunction
ü Fibroblast growth factor 23
ü Obstructive sleep apnea
ü Failed native kidneys
ü Sympathetic overactivity
These factors might also be classified as
Immunological factors including: DGF, Immunosuppression (CNI, Corticosteroids), Acute or chronic rejection
Non-immunological Factors:
ü Surgical related: Intraoperative volume administration, Transplant renal artery stenosis
ü related to the Donor: Hypertensive kidney, Family history of HTN in donor, Transplant renal artery stenosis
ü related to the Recipient: Pre-existing HTN, Renal allograft dysfunction, Dietary sodium intake, Metabolic syndrome, TRAS, OSA, Failed native kidneys, Sympathetic over activity
Blood Pressure Management: target ≤130/80
Non-pharmacologic:
ü Dietary control
ü Life style modification: exercise, and stress reduction
Pharmacological: antihypertensive medications:
Diuretics : not the first line
Loop ,Thiazide:
· Used for volume control
· May use with ACEI or ARB in TRAS
· Renal sodium excretion defect in CsA-induced HTN
CCB calcium channel blocker
· Afferent arteriolar vasodilatation
· May improve renal allograft function and lower DGF but inconclusive
*Non-dipyridamole CCB is CYP450 inhibitor and increases CNI level
ACEI/ARB
· Anti-proteinuric
· Cardioprotection
· May use with diuretic in TRAS
Beta-blockers: cardioprotection
Mineralocorticoid receptor antagonists:
– Systolic dysfunction – Safe with using ACEI and ARB but increase hyperkalaemia
Alpha1 antagonist :Generally, not the first line
Alpha2 agonist
· Lower plasma renin activity that modulated renal vascular resistance and lower MAP.
· No change in GFR and effective renal plasma flow.
Other Interventions: for resistant HTN:
Specific to certain etiologies, such as Transplant Renal Artery Angioplasty ± Stenting
Bilateral Native Nephrectomy
Renal sympathetic denervation
During perioperative time: close monitor to BP, with adequate pain control to avoid low or high reading. if needed parenteral antihypertensive medication can be used (labetalol example)
At hospital discharge advice about weight control, salt low, and general dietary plan with nutritionist
Follow up visit and BP regular measuring to diagnose any HTN early.
When BP reading is high: looking for drug level, assessment of graft function, volume status and all other possible factors
Medication: CCB is commonly used as first line, we avoid ACEi specially at early post-transplant period so not to be confused if creatinine readings start to rise.
Summary
This article is about hypertension following kidney transplant. The treatment options for resistant hypertension post transplant as well as antihypertensive medications and their mechanism of action has also been discussed.
The risk factors that make a recipient more susceptible than others to hypertension following kidney transplant include the presence of 3 factors listed below :
Hypertension post transplant can occur in different periods :
In the immediate period, volume overload contributes to development of hypertension. Hypertension can develop in any period associated with donor kidneys or immunosuppressive medications.
Factors contributing to development of post transplant hypertension according to different time periods mentioned above :
Immediate post transplant period
Early post transplant period
Late post transplant period
Two common causes of resistant but treatable hypertension following transplant include :
An important factor contributing to hypertension in the late post transplant period includes chronic renal allograft dysfunction.
Increase in fibroblast growth factor 23 or FGF23 is associated with increased cardiovascular and all cause mortality in kidney recipients.
One of the major issues adding to the burden of hypertension is improper pain management. NSAIDs are to be avoided in the post transplant phase and opioids are acceptable. NSAIDs can cause negative renal effects such as reduced renal plasma flow.
24 hour measurement of BP is essential but it is inconvenient and not utilized in many centers.
Bilateral native kidney nephrectomy can be a treatment option for resistant post transplant hypertension. Evidence suggests that recipients who have undergone native nephrectomy pre or post transplant have decreased BP compared to those without native nephrectomy. Native renal denervation can also be used.
Antihypertensive medications that can be used include diuretics, calcium channel blockers, beta blockers, RAAS blockers such as ACEi, ARBs, mineralocorticoid receptor antagonists.
Further research is needed to develop stronger evidence concerning the pathogenesis of post transplant hypertension, appropriate measurement of BP, effective pain management, appropriate dosing and application of antihypertensive medications and the surgical methods of treatment for resistant post transplant hypertension.
Introduction
Hypertension Post-transplantation very common and complex pathology, many immunological and nonimmunological factors related to transplantation can lead to hypertension in addition to medication effects, in particular, CNI, transplant renal artery stenosis (TRAS), OSA, metabolic syndrome, dyslipidemia, obesity, and DM, it carries high cardiovascular risk and impacts the graft survival, post-transplant hypertension can be classified as early, immediate and late after TX, which usually associated with chronic graft dysfunction .this article review the causes, pathogenesis of hypertension post-transplantation, classification and treatment options including pharmacological and interventional angioplasty or renal denervation and native kidney nephrectomy in the resistant type of hypertension based on the available evidence from the guideline.
Definition of post-kidney transplantation
The definition and prevalence Of HTN post-transplantation are quite variable between studies due to variation in the definition and it’s in the range between 25-90%, however, target Bp should be < 130/80
1. Persistent high blood pressure
2. recovered HTN,
3. persistent normotension,
4. post-TX HTN, and with aging isolated systolic HTN is also common, Post-transplant HTN is associated with increased CVD morbidity.
Post-transplant HTN
Immediate post-transplant period due to IVF peri-and postoperative time which leads to volume overload
Induction immunosuppression medications like steroids with increased sympathetic overactivity
Rebound HTN especially those on BB,
post-operative pain management also due to sympathetic overactivity.
Early post-transplantation
Between 24-52 weeks post-TX, involve many factors
Weight gain
immunosuppression therapy (CNI, Steroids’ )
Hypertensive kidney donor
Transplant RAS
CNI Induced HTN
Change of Vascular tone, with arteriolar vasoconstriction due to the effect of endothelin, not angiotensin 11, and reduced vasodilator like nitic oxides
CNI induces salt-sensitive HTN via activation of the WNK- SPAK-NCC pathway similarly to a rare genetic form of HTN, called familial hyperkalemic hypertension (FHHt, also called Gordon syndrome or pseudohypo-aldosteronism type 2), so patient will have normal anion gap hyperkalemic acidosis with low fractional excretion of chloride with hypercalciuria and thiazide diuretics will be effective for CNI induced hypertension
Late post-transplantation
Chronic allograft dysfunction
Fibroblast growth factor (GF23) is considered an independent risk factor for graft loss
OSA post-transplantation more in males with higher BMI, DM, impaired graft function, on hypnotic medications and it’s associated with higher CVD, PVD, and CVA risk
Failed native kidneys
Sympathetic overactivity
RAS, renal artery stenosis
So in summary post-transplantation hypertension is quite common and variable prevalence between 70-90% in the era of CNI and can be classified as an immunological risk for HTN including DGF acute or chronic rejection immunosuppression ( CNI ,steroids )
the non-immunological risk factors include
donor-related factors ( HTN kidney donor or FH of hypertension in the donor, ARAS,
recipient-related factors (preexisting HTN, ARAS, medications
surgical factors ( volume load , RAS)
post-transplant hypertension is complex and is a result of the interplay between
immunological and non-immunological factors. Post-transplant hypertension can be
divided into immediate, early, and late post-transplant periods. a BP of <130/80 mmHg is a reasonable target.
kidney transplant recipients can be divided into four groups: persistent HTN, recovered HTN, persistent normotension, and post-transplant HTN.
Common causes of post-transplant hypertension according the period of transplant
a) immediate post-transplant
1- hypervolemia
2- induction Is medications
3- rebound hypertension
4- inadequate pain control
b) early post-transplant
1- weight gain
2- CNI and /or steroids medications
3- hypertensive transplant donor
4- TRAS
c) late post-transplant
1- Chronic allograft dysfunction
2- failed native kidneys
3- fibroblast growth factor 23
4- OSA
5- sympathetic overactivity
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
Elevated BP is associated with poorer renal allograft and patient outcomes
BLOOD PRESSURE MANAGEMENT
Non-pharmacologic interventions, such as diet, exercise, and stress reduction, should always be part of treatment of HTN.
Anti-hypertensive medications tailored according to patient condition and co-morbid
Procedural or surgical interventions; Specific treatment modalities
• Transplant renal artery angioplasty ± stenting
• Continuous positive airway pressure (CPAP)
• Bilateral native nephrectomy
• Native renal denervation
– In each opd visit
– -if patient high risk to have high bp and can’t detect it in the opd , so need ambulatory monitoring
– I don’t consider high bp unless confirmed by 3 readings in different occasions with physical and mental rest, or through 24-hour monitoring
– Educate the patient about the non-pharmacological measures
– If patient needs starting antihypertensive medications so should consider other comorbids, eGFR, proteinuria
– If resistant so need more investigations to detect the cause
After successful kidney transplantation, hypertension is one of the most common cardiovascular co-morbidities. People with metabolic diseases (diabetes, obesity etc) are more commonly affected. Prevalence of post-transplant HTN ranges from 24 to 90%.
Both immunological and non-immunological factors play a key role in the pathogenesis of post-transplant hypertension.
Post-transplant hypertension classification is divided into immediate, early, and late post-transplant periods and this classification is used to help clinicians to choose the appropriate treatment and to determine the etiology.
In the Immediate post-transplant period patient may present hypertension secondary to: -Volume overload following intravenous fluid administration (peri-transplant
hypervolemia particularly in patients with delayed graft function)
-Steroids (result from alterations in intrinsic pressor response leading to arterial vascular
resistance)
-Rebound hypertension (result of sympathetic Overactivity following a sudden
discontinuation of antihypertensive therapy)
-Inappropriate pain management (via sympathetic nervous system activation, leading to
increases in peripheral vascular resistance, heart rate, and stroke volume).
In the early post operative period it was found that systolic HTN (140 mmHg) occurred at the mean duration of 26–50 weeks after kidney transplantation.
The most common factors that contribute to hypertension during this period include:
-Weight gain
-Steroids
-Calcineurin Inhibitors (increased vasoconstriction and impaired vasodilation contribute
to CNI-induced post-transplant HTN, Renal vasoconstriction and sympathetic excitation
with subsequent sodium retention)
-Hypertensive Donor Kidney (Salt intake can lead to water retention and HTN, especially
in salt sensitive individuals)
-Transplant Renal artery Stenosis (1–5%of post-transplant HTN is secondary to TRAS
and is generally diagnosed between 3 and 24 months post transplantation).
In the Late Post-transplant Period, causes of Hypertension include:
-Chronic Renal Allograft Dysfunction and OSA. With Chronic renal allograft dysfunction
as part of chronic kidney disease affecting the graft there is an increase FGF23 which is
associated with increased cardiovascular and all-cause mortality in kidney transplant
recipients. However, remains unclear the relation between post-transplant hypertension
and increased FGF23.
Very low pre-transplant SBP (<110 mmHg) and DBP (<50 mmHg) are associated with a
decrease in renal allograft loss. During the post-transplant period, elevated BP is
associated with poorer renal allograft and patient outcomes. Kidney transplant
recipients with left ventricular hypertrophy (LVH) or HFpEF have increased morbidity
and mortality and are at high risk for cardiac-related events.
BP can be standardized with office blood pressure (OBP) which is the mean of three non-invasive BP measurement, the home blood pressure monitoring (HBPM) recording at least twice the daily average of two home blood pressure readings over a minimum of 4 days and the 24- h ambulatory blood pressure monitoring (24-h ABPM) (record and averages multiple readings over a 24 h period).
Management of hypertension in renal transplant patient involve pharmacological and non-pharmacological approach. A reasonable target BP in renal transplant patient is < 130/80 mmHg.
Non pharmacological approach include physical activity, low salt diet and stress reduction.
Pharmacological approach include antihypertensive medications:
-Diuretics: Not commonly used as the first line antihypertensive medication in kidney
transplant recipients. Loop Diuretics are used for Volume control rather than BP control
is the indication in kidney transplant recipients, especially during immediate and early
post- transplant periods. Thiazides may theoretically control CNI-induced HTN since
CNI-induced HTN is salt sensitive
-Mineralocorticoid Receptor Antagonists (MCRA): not commonly used in kidney
transplant recipients, especially in case of declining graft function. Common side
effects of MCRA is hyperkalemia.
-Beta Blockers: cardioprotective effects and survival benefit both in the general and
ESRD populations. BBs are the most common used antihypertensive medication in
kidney transplant recipient. Kidney transplant recipients on BB seems to have a
significant survival advantage compared to those not on BB. Protective mechanism of
beta-blocker is through inhibition of the sympathetic nervous system. BB mask
symptoms of hypoglycemia and thyrotoxicosis and may worsen lipid profiles.
Possible side effect include Hyperkalemia
-Calcium Channel Blockers (CCB): its vasodilatory effect can counteract the
vasoconstrictive effect of CNIs and improve BP control. Prevent post-transplant acute
tubular injury (ATI) or DGF. Diltiazem has lower incidence of ATI, higher GFR with
primary function, lower incidences of rejection at 1 month post-transplant. Diltiazem
increases CsA level. Recent systematic review and meta-analysis of 60 trials including
3,802 patients showed that, compared to placebo or no treatment, CCB decreased graft
loss [risk ratio (RR) of 0.75, 95% confidence intervals (CI) 0.57–0.99] and increased
GFR [mean difference (MD) 4.5 mL/min, 95% CI 2.2–6.7]. CCB can cause peripheral
edema and muscle weakness (particularly when used in combination with steroids)
and gum hyperplasia (especially when calcium channel blockers are used with CsA)
-Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor Blockers
(ARB): Data regarding the benefits of ACEI or ARB therapy in terms of patient or renal
allograft survival are insufficient. RAAS activation is associated with interstitial fibrosis
and tubular atrophy (IF/TA) (IF/TA are one of the most common causes of renal allograft
loss). Perindopril seems to prevent cortical interstitial expansion (marker of fibrosis in
CKD patients with diabetic nephropathy). Despite their antiproteinuric effect during the
immediate and the early post-transplant period, they are generally not used as they
decrease GFR.
–Alpha 1 Antagonist: They reduce BP by decreasing peripheral vasoconstriction. They
are not commonly used as initial or as a single antihypertensive agent in kidney
transplant recipients.
-Alpha2 Agonists: Centrally acting alpha2 agonists work on presynaptic alpha2
adrenoceptors in the central nervous system. They suppress the central sympathetic
activity. methyldopa and clonidine are the most commonly used alpha2 agonist.
methyldopa, as a monotheraphy is associated with antihypertensive tolerance, edema,
and weight gain. Clonidine is also associated with weight gain and progressive
resistance with continued use.
Other Non pharmacological interventions for BP control include:
-Bilateral native nephrectomy: In kidney transplantation, the presence of failed native
kidneys is associated with post-transplant resistant HTN. ACEIs and native
nephrectomy may need to be considered
-Native renal denervation: In failed native kidney there is a sympathetic overactivity
which may lead resistant HTN.
-Surgical Renal Denervation by Bilateral Native Nephrectomy
We encourage life style changes in the first instance. In terms of pharmacological treatment we usually start with CCB. If patient has underlying cardiac disease or AF or tachycardia we prefer BB. We consider ACEinhibitor anr ARB 3 months post transplant for patient with stable graft function and proteinuria. We monitor renal profile 7 to 10 days after commencing ACEinh/ARB to ensure the graft function remains at its baseline. If there is a drop of eGFR within 20-25 % from baseline renal function we will continue on ACE inh/ARB otherwise we reduce the dose or we stop the medication. We consider ACE inh for hypertension associated with Polycythemia
In case of volume dependent hypertension we use diuretics (thiazide). As a second line for resistant hypertension we add alfa blockers
Introduction:
kidney transplantation is the treatment of choice for end-stage renal disease patients. Similar to non-transplant patients, cardiovascular diseases remain the leading cause of morbidity and mortality in kidney transplant recipients. Hypertension is a usual finding in this population and one of the most common risk factors for CVD.
Epidemiology of post-transplant hypertension:
The overall prevalence of post-transplant HTN has ranged from 24 to 90%. Depending on the definition and methods of blood pressure measurement utilized, the prevalence of post-transplant HTN has been widely reported, and it has generally increased over time.
Definition of post-transplant hypertension:
It can be defined as a persistently elevated BP or normotension with antihypertensive medications after successful kidney transplantation.
The cutoff for normal BP post-transplant differs; different studies have defined post-transplant HTN with different cutoff levels for systolic and diastolic blood pressure and different requirements for the use of antihypertensive medications. in addition, the presence or absence of HTN during the pre-kidney transplant period may further categorize kidney transplant recipients into four groups: persistent HTN, recovered HTN, persistent normotension, and post-transplant HTN.
Pathogenesis of post-transplant HTN:
Outcomes of hypertension after kidney transplantation:
Cardiovascular Outcomes-Related to Post-transplant Hypertension:
BP management:
BP control during the peri-transplant period:
Loop diuretics:
Volume control rather than BP control is the indication for loop diuretics in kidney transplant recipients, especially during immediate and early post-transplant periods.
Loop diuretics can also provide prognostic value regarding renal allograft function in the immediate post-transplant period. An inadequate response, urine output <350 ml within 4 h, to a single IV furosemide dose of 1.5 mg/kg given 3 h after renal allograft anastomosis predicts increased risk of DGF.
Additional RCTs are required to determine the efficacy and safety of loop diuretic in kidney transplant recipients.
Thiazides:
Uncommon to be used in the management of kidney transplant recipients because of their metabolic side effects which include hyperglycemia, hyperuricemia, hypercalcemia, and hyponatremia.
Thiazides, however, may theoretically control CNI-induced HTN but increase serum magnesium when used with CNI.
Thiazides may be considered for kidney transplant recipients with CNI-induced salt-sensitive HTN and hypomagnesemia.
Mineralocorticoid Receptor Antagonists:
have CV benefits and antiproteinuric effects but are not commonly used antihypertensives in kidney transplant recipients, especially with reduced graft function.
Hyperkalemia is a common side effect of MCRA, and it may be worse in kidney transplant recipients who have CNI-induced hyperkalemia.
RCTs showed CV benefits in renal transplant patients. The possible protective mechanism of beta-blocker is via mitigation of the sympathetic nervous system, which is stimulated in failed native kidneys. Also they can cause metabolic side effects, including proteinuria, hyperkalemia, and masking of hypoglycemic symptoms. Therefore, caution should be used when using beta blockers in kidney transplant recipients who are at risk to develop these side effects.
Theoretically, their vasodilatory effect can counteract the vasoconstrictive effect of CNIs and improve BP control. Also, prevent post-transplant acute tubular injury or DGF..
ACEi & ARB:
Although ACEIs and ARBs provide antiproteinuric effects, they are generally not the drugs of choice during the immediate and early post-transplant periods. This is mainly because they are known to decrease GFR.
Are rarely used as the initial or as a single antihypertensive agent in kidney transplant recipients. there is no evidence that alpha1-antagonists provide a superior antihypertensive effect or slow the progression of renal allograft dysfunction when compared to other antihypertensive medications.
Rebound HTN is common after discontinuation of clonidine, and patients who are on clonidine prior to kidney transplant tend to have uncontrolled HTN resulting from this rebound phenomenon.
OTHER MANAGEMENT FOR BLOOD PRESSURE:
Native Nephrectomy
kidney transplant recipients with resistant HTN, ACEIs and native nephrectomy may need to be considered.
Native Renal Sympathetic Denervation:
Renal and systemic sympathetic hyperactivity contributes to the pathophysiology of resistant HTN. The effect of RDN on BP control was established.
Surgical Renal Denervation by Bilateral Native Nephrectomy:
native nephrectomy for the purpose of BP control in kidney transplant recipients should be performed in select patients with severely uncontrolled post-transplant HTN who, without treatment, would have deterioration of renal allograft function or be at increased risk of CV complications.
Catheter Ablative Renal Denervation
complete RDN by bilateral native nephrectomy in kidney transplant recipients is invasive and carries a risk of additional operation, native RDN is another option, and it should be reserved for selected patients.
By antihypertensive medications starting with calcium channel blockers as the first line, then B-blockers as the second line, if additional antihypertensives are required, we use alfa methyl dopa.
We do not use ACEi and ARB in the early post-transplant period.
Hypertension is one of the most common cardiovascular co-morbidities after successful kidney transplantation.Post-transplant hypertension can be divided into
immediate,
early, and
late post-transplant periods.
Volume overload from intravenous fluid administration is common during the immediate post-transplant period and commonly contributes to hypertension seen early after transplantation.
Immunosuppressive medications
donor hypertensive kidneys are associated with post-transplant hypertension occurring at any time point after transplantation.
Transplant renal artery stenosis (TRAS) and obstructive sleep apnea (OSA) are recognized but common and treatable causes of resistant hypertension post-transplantation.
During late post-transplant period, chronic renal allograft dysfunction and associated increased fibroblast growth factor 23 (FGF23) is associated with increased cardiovascular and all-cause mortality in kidney transplant recipients.
There is no consensus that what is the optimum target BP in post transplant period however a BP of <130/80 mmHg is a reasonable target.
Different medications used for this purpose have there own advantages and disadvantages.Most commonly used drugs are
Diuretics
MRA
Beta Blockers
Calcium Channel blockers
ACEi/ARBs
Alpha 1 antagonists
Alpha2 Agonists
Calcium channel blockers are more widely used and ACEi and ARBs are mostly avoided in early transplant period.
bilateral native nephrectomyis another treatment option for resistant post-transplant hypertension. Native renal denervation offers promising outcomes for controlling resistant hypertension with no significant procedure-related complications.
Stenting for TRAS and management of OSA should always be considered
The choice of antihypertensive medication requires the transplant physician to consider immunological factors into account as well.
At our center mostly we manage it with calcium channel blockers and then do add on therapy. We don’t use ACE/ARB till six months post transplant
Hypertension is one of the most common cardiovascular comorbidities
Post kidney transplant HTN can be defined as a persistently elevated BP or normotension with the use of antihypertensive medication after successful kidney transplantation.
In this reveiw , post kidney transplation HTN refers to persistent and de novo post transplant HTN.
Causes:
Immediate post transplant period:
Early post transplant period:
This means HTN in between 24 to 52 weeks of post transplantation.
causes are:
1.Weight gain.
2.Calcineurin inhibitors.
3.steroids.
4.Hypertensive donor kidney
5.Transplant renal artery stenosis
Late post transplant period:
Blood pressure measurement:
Office blood pressure
Home measured blood pressure monitoring
24 hour ambulatory blood pressure monitoring
Mnagement
Non pharmacologic:
Diet
Exercise
Stress reduction
Pharmacologic therapy:
Diuretics
Calcium channel blockers
Beta blockers
Renin angiotensin aldosteron system blocke
Unless there is contraindication, kidney transplantation is the treatment of choice for advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD)
Survival benefit and quality of life are significantly improved after a successful kidney transplantation with renal allograft function.
Since the introduction of calcineurin inhibitors (CNI) in the 1980’s, short-term renal allograft survival has greatly improved
Several immunological and non-immunological causes contribute to long-term renal and patient survival outcomes.
Similar to non-transplant patients, cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality in kidney transplant recipients
Hypertension (HTN) is a usual finding in this population and one of the most common risk factors for CVD
EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION
Overall prevalence of post-transplant HTN has ranged from 24 to 90%
The prevalence of post-transplant hypertension increased could be due to introduction of cyclosporine (CsA)
DEFINITION OF POST-TRANSPLANT HYPERTENSION
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation
kidney transplant recipients are categorized into four groups:
(1) Persistent HTN occurs in patients with HTN both in the pre- and posttransplant periods
(2) recovered HTN have HTN only during the pre- but not the post-transplant period.
(3) Persistent normotensive patients have no history of HTN preceding transplant and remain normotensive post-transplant.
(4) Post-transplant HTN requires developing de novo HTN after kidney transplant
The most common phenotype of HTN in elderly patients isolated systolic HTN (defined as SBP ≥140 and DBP)
Linear increase in systolic and diastolic BP occurs with age until the fifth or the sixth decades of life when SBP continues increasing, but DBP tends to decrease
Diastolic HTN is defined as DBP of ≥90 mmHg, with a SBP <140 mmHg, and is more common in younger,
sedentary individuals with a higher body mass index (BMI)
After SPRINT trial, HTN was re-defined as (SBP) >130 or DBP >80 mmHg
A recent 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a target BP of
PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION
Immediate Post-transplant Period:
· Peri-transplant Hypervolemia
· High-Dose Steroids
· Rebound Hypertension
· Inappropriate Pain Management
Early Post-transplant Period:
· Weight Gain
· Calcineurin Inhibitors
· Increased renal sodium transport handling
· Steroids
· Hypertensive Donor Kidney
· Transplant Renal Artery Stenosis (TRAS)
Late Post-transplant Period
· Chronic Renal Allograft Dysfunction
· Fibroblast Growth Factor (FGF) 23
· Obstructive Sleep Apnea
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
Very low pretransplant SBP (<110 mmHg) and DBP (<50 mmHg) are associated with a decrease in renal allograft loss.
During the post-transplant period, elevated BP is associated with poorer renal allograft and patient outcomes.
Cardiovascular Outcomes-Related to Post-transplant Hypertension
Kidney transplant recipients with left ventricular hypertrophy (LVH) or HFpEF have increased morbidity and mortality and are at high risk for cardiac-related events
Renal insufficiency is involved in the pathogenesis of HFpEF (126) and causes salt-sensitive HTN
Uncontrolled HTN after kidney transplantation leads to structural damage to both the renal allograft and heart eventually resulting in decreased renal and cardiac functions.
BLOOD PRESSURE MEASUREMENT
· office blood pressure: the mean of three non-invasive BP measurements
· home blood pressure monitoring: recording at least twice the daily average of two home blood pressure readings over a minimum of 4 days
· 24- h ambulatory blood pressure monitoring
BLOOD PRESSURE MANAGEMENT
A. Non-pharmacologic interventions: diet, exercise, and stress reduction
B. PHARMACOLOGICAL:
1-Loop Diuretics:
· used for Volume control rather than BP control.
· can be used to control both volume and BP in patient with pulmonary congestion and HTN.
· increase risk of UTI during the first 5 years after kidney transplantation
2- Thiazides:
· may cause hyperglycemia, hyperuricemia, hypercalcemia, and hyponatremia
· can be used in the setting of volume overload and concomitant hypomagnesemia, to reduce the hypomagnesemic effect of CNI therapy
3- Mineralocorticoid Receptor Antagonists
· may be a new option for BP control in individual with CNI-induced HTN and proteinuria.
· Hyperkalemia is a common side effects and it may be worse in kidney transplant recipients who have CNI-induced hyperkalemia
4- Beta-Blockers
· In kidney transplant recipients, betablockers are the most common used antihypertensive medication
· has additive effect on ACEI or ARB with greater survival in kidney transplant patients on this combination compared to those who received either medication alone or neither
· they can cause proteinuria, hyperkalemia, and masking of hypoglycemic symptoms
5- Calcium Channel Blockers
· In addition to blood pressure control, they prevent post-transplant acute tubular injury (ATI) or DGF
· a recent systematic review showed that calcium channel blockers decreased graft loss and increased GFR
· can result in peripheral edema and muscle weakness especially when used in combination with steroids. Gum hyperplasia is also more common when CCB are used with CsA
6- Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor Blockers (ARB)
· Although ACEIs and ARBs provide antiproteinuric effect, they are generally not the drugs of choice during the immediate and early post-transplant periods
· they are known to decrease GFR
· can lead to regression of LVH in kidney transplant recipients
7- Alpha1-Antagonists
· rarely used as the initial or as a single antihypertensive agent in kidney transplant recipients
· there is no evidence that alpha1-antagonists provide superior antihypertensive effect or slows progression of renal allograft dysfunction when compared to other antihypertensive medications
8- Alpha2 Agonists (centrally acting)
· When used as monotherapy, methyldopa is associated with antihypertensive tolerance, edema, and weight gain
· Clonidine is also associated with weight gain and progressive resistance with continued use
· rebound HTN is common after discontinuation of clonidine
C. OTHER MANAGEMENT FOR BLOOD PRESSURE
· Native Nephrectomy: for resistant HTN
· Native Renal Sympathetic Denervation
· Surgical Renal Denervation by Bilateral Native Nephrectomy
· Catheter Ablative Renal Denervation
How do you manage hypertension after kidney transplantation in your workplace?
·
Early post transplantation: be sure that patient is not overloaded, adjust CNI level. If Bp still high I would start with amlodipine and or bisoprolol if there was tachycardia or heart failure
· If the patient developed lower limbs oedema after adding CCB, I would change it to centrally acting Alpha2 Agonists, or alpha 1 blocker, in early stage
· After 1 year I may add an ACEi or ARB if the patient had L.L edema or proteinuria or polycythemia
· When I use ACEi or ab ARB, I repeat creatinine after one week, and then one month. I stop it if creatinine elevated more than 20% of the base line
· If the patient is overloaded and hypertensive, I may give thiazide or furosemide (if there is renal impairment)
Introduction
Hypertension Post-transplantation very common and complex pathology, many immunological and nonimmunological factors related to transplantation can lead to hypertension in addition to medication effects, in particular, CNI, transplant renal artery stenosis (TRAS), OSA, metabolic syndrome, dyslipidemia, obesity, and DM, it carries high cardiovascular risk and impacts the graft survival, post-transplant hypertension can be classified as early, immediate and late after TX, which usually associated with chronic graft dysfunction .this article review the causes, pathogenesis of hypertension post-transplantation, classification and treatment options including pharmacological and interventional angioplasty or renal denervation and native kidney nephrectomy in the resistant type of hypertension based on the available evidence from the guideline.
Definition of post-kidney transplantation
The definition and prevalence Of HTN post-transplantation are quite variable between studies however target Bp should be < 130/80 Persistent high blood pressure or normotensive with medications after kidney transplantation further classification of hypertension can be categorized as persistent HTN, recovered HTN, persistent normotension, and post TX HTN, and with aging isolated systolic HTN also common, Post-transplant HTN associated with increased CVS morbidity.
Post-transplant HTN
Immediate post-transplant period due to IVF peri-and postoperative time which leads to volume overload, induction immunosuppression medications like steroids with increased sympathetic over activity, rebound HTN especially those on BB, and deficient pain control also due to sympathetic overactivity
Early post-transplantation
Between 24-52 weeks post-TX, involve many factors
Weight gain, immunosuppression therapy (CNI, STEROIDS), hypertensive kidney donor, transplant RAS
CNI Induced HTN
Change of Vascular tone, with arteriolar vasoconstriction and reduced vasodilator
Late post-transplantation
Chronic allograft dysfunction
FBGF23
OSA
Failed native kidneys
Sympathetic overactivity
RAS , renal artery stenosis
Why we need to control Hypertension After Kidney Transplantation
• Several studies have demonstrated an association between post-transplant HTN, CV risk, and renal allograft failure.
• Opelz et al. conducted a retrospective study of 29,751 kidney transplant recipients followed for over 7 years. Increased post-transplant SBP and DBP were associated with progressively decreased renal allograft function and death-censored chronic graft failure
• There is insufficient information about CV and mortality outcomes related to isolated diastolic HTN in kidney transplant recipients.
Epidemiology Of Post-transplant Hypertension
• the prevalence of post-transplant HTN has been widely reported,
• The exact prevalence is difficult to diagnose because the definition and methods of blood pressure (BP) measurement in studies didn’t share the same criteria but it has generally increased over time. This greater incidence of post-transplant hypertension may be related to the introduction of cyclosporine
Definition Of Post-transplant Hypertension
· the definition of HTN in kidney transplant recipients remains controversial, and hard outcomes related to BP levels are still limited.
· A recent 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a target BP of <130/80 mmHg.
· Until there is stronger evidence of an association between BP level and outcomes in kidney transplant recipients, a BP ≥130/80 mmHg may be a reasonable definition for HTN in this population.
PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION
Immediate Post-transplant Period
Rebound Hypertension
it is common practice to hold some if not all of the pre-transplant BP medications in an effort to avoid early hypotension. However, this abrupt discontinuation of antihypertensive therapy can lead to rebound hypertension, an elevated BP above pretreatment levels, as a result of sympathetic overactivity.
2. beta-blockers
Early Post-transplant Period
• the vasoconstrictive effect on renal or systemic vasculature remains unclear.
• Increased renal sodium transport handling: Sympathetic nervous system activation. CSA causes sympathetic excitation and subsequent sodium retention(Sodium Chloride Cotransporter (WNK-SPAKNCC) pathway
2. . Transplant Renal Artery Stenosis (TRAS):
o It’s associated with poorer transplant outcomes and CV complications including post-transplant HTN and early treatment causes reverse those negative outcomes.
o TRAS may occur at any time after kidney transplantation but is generally diagnosed between 3 and 24 months post-transplantation( Immunological factors leading to vascular endothelial dysfunction can cause TRAS. Other transplant-related risk factors have been reported including cytomegalovirus (CMV) infection)
o Diagnosis: Renal artery angiography remains the gold standard diagnostic test for TRAS, but it is invasive and can lead to CIN. Carbon dioxide (CO2) angiography can mitigate some of the risks of CIN, but, in most cases, small amounts of IV contrast are still required to attain sufficiently detailed images.
o Three therapeutic options for TRAS are pharmacological therapy alone or pharmacologic therapy in addition to renal artery angioplasty with stenting or surgical revascularization
o Medical antihypertensive therapy may be utilized to control blood pressure. Statins and acetylsalicylic acid may also be part of pharmacological therapy although there is no clear evidence for these use specifically in TRAS
o Indication for intervention
o Patients with worsening serum creatinine and/or uncontrolled HTN attributable to TRAS
o There is no randomized controlled clinical trial (RCT) comparing the efficacy of angioplasty ± stenting vs. surgical revascularization vs. pharmacological therapy alone in the kidney transplant population.
Late Post-transplant Period
• Obstructive Sleep Apnea
• Sleep disorders Evaluation in Patients after kidney Transplantation (SLEPT) : In this study, kidney transplant patients with OSA required a significantly higher number of antihypertensive medications and tended to have higher SBP as compared to non-OSA patients
• They share the same risk factors including male gender, obesity, use of hypnotic drugs, presence of severe comorbidity (e.g., heart disease, cerebrovascular disease, peripheral vascular disease, diabetes mellitus), and impaired kidney function (indication for a sleep study)
• If any of these diseases is uncontrolled or progresses the other two conditions tend to worsen or become more difficult to manage. Therefore, appropriate management of OSA is an essential component of the antihypertensive therapy in kidney transplant recipients who later develop renal allograft dysfunction, especially with resistant HTN.
BLOOD PRESSURE MEASUREMENT:
• it may frequently be unreliable due to variation of physiologic response to internal and external stimuli as well as inappropriate BP measurement techniques.
• Reliable BP measurement should be mandatory in clinical practice and can be standardized with the following definitions
• office blood pressure (OBP): the mean of three BP measurements
• home blood pressure monitoring (HBPM): recording at least twice the daily average of two home blood pressure readings over a minimum of 4 days
• 24- h ambulatory blood pressure monitoring (24-h ABPM): dippers, non-dippers, and reverse dippers
• Compared with OBP, a 24-h ABPM led to 61% disagreement in diagnosis (58% and 3% due to masked and white-coat HTN, respectively).
• Although a 24-h ABPM can provide useful information to diagnose patterns of HTN like white coat and masked HTN, OBP and HBPM are more commonly used in clinical practice.
• Since transplant renal allografts are very sensitive to BP hemodynamic changes, HBPM appears to be a commonly utilized method of following BP after kidney transplantation. Based on study addressed by Mallamaci F. (2018): revealed a higher correlation between a 24-h ABPM and HBPM than 24-h ABPM and OBP
• Although HBPM is widely available, better correlated to 24-h ABPM, and superior to OBP when predicting hard outcomes, we used HBPM in conjunction with OBP for our kidney transplant patients to minimize misclassification of HTN diagnosis, monitor possible white coat or masked HTN, and adjust antihypertensive medications.
Blood Pressure Management
• PHARMACOLOGICAL MANAGEMENT
• there is no drug of choice for BP control after kidney transplantation.
• Several factors are involved in selecting the appropriate antihypertensive medications including immunologic and non-immunologic factors as well as the time after kidney transplantation.
• Different from the non-transplant CKD population, beta blockers and calcium channel blockers are the most frequently used combination in kidney transplant recipients. Beta-blockers provide a cardioprotective effect for kidney transplant patients, who likely have underlying CAD.
• Calcium channel blockers have the vasodilatory effect that counteracts the vasoconstrictive effect of CNIs.
• ACEIs and ARBs are not routinely used as antihypertensive medications in kidney transplant recipients. This is especially true during the early post-transplant period when baseline renal allograft function is not well-established. They can, however, be considered when there is a specific indication for their use, such as proteinuria and posttransplant erythrocytosis.
• diuretics are not generally used as the first line for BP control in kidney transplant recipients.
• we routinely use dihydropyridine calcium channel blockers and/or beta-blockers as first-line antihypertensive medications.
• Since the majority of patients do not achieve BP control during the immediate or early post-transplant period, the combination of dihydropyridine channel blockers with beta-blockers is commonly used in our transplant center.
• Once renal allograft function is established and stable, we consider adding or replacing ACEI or ARB for dihydropyridine channel blockers and beta-blockers if there are appropriate indications, such as proteinuria or posttransplant polycythemia
• Until there is strong clinical outcome evidence in terms of CV, patients, or renal allograft survival, BP targets should be individualized, taking into account immunologic and nonimmunologic factors that are contributing to HTN in each kidney transplant recipient.
• OTHER MANAGEMENT FOR BLOOD PRESSURE
a. Native Nephrectomy
The majority of these studies were notably conducted in patients with ADPKD as the cause of ESRD with resistant HTN, defined as uncontrolled BP with at least three antihypertensive medications of which one is a diuretic. Apart from renovascular and hormonal causes of secondary HTN (but should not be routine practice)
b. Native Renal Sympathetic Denervation
single-center RCT with 6-month follow-up of 18 kidney transplant recipients with resistant HTN compared (efficacy of renal sympathetic denervation as compared to medical therapy alone).
RDN group had
• a significantly decreased office SBP of 23.3 ± 14.5 mmHg
• a higher proportion of patients who converted from non-dippers to dippers. Nocturnal BP recorded with 24-h ABPM, but not daytime BP, was also lower by 10.38 ± 12.8 mmHg in the RDN group, though this was not statistically significant.
• Safety endpoints including changes in renal allograft function and renovascular complications were not different between the 2 groups. Although native RDN is effective in controlling BP, larger RCTs with a sham-control are required.
Prevalence of Hypertension in KTR is ranging from 24-90%, occurring in patients with other metabolic diseases like diabetes mellitus, obesity, and hyperlipidaemia. It can be classified: persistent hypertension, recovered hypertension, persistent normotension and post-transplant hypertension The prevalence of persistent hypertension and post-transplant hypertension is 40% and 19% respectively.
Post-transplant hypertension can be defined as immediate-, early (24 to 52 weeks) and late- (after 1 year).
· Risk factors for hypertension in immediate post-transplant:
· Overload-due to intravenous fluids, especially in patients with delayed graft function
· use of induction agent and high dose steroids-increasing vascular resistance
· inadequate analgesia caused increased pain -due to sympathetic overactivity
· rebound hypertension -due to sudden stoppage of beta blockers and clonidine
Risk factors for hypertension in early post-transplant period:
· obesity and weight gain,
· calcineurin inhibitor use
· steroid use
· donor hypertension / if donor has a family history of hypertension
· transplant renal artery stenosis-immunological and non-immunological causes
Hypertension in late post-transplant period is associated with chronic graft dysfunction (persistent antibody mediated rejection, Interstitial fibrosis, and tubular atrophy, thrombotic microangiopathy and disease recurrence), obstructive sleep apnoea (due to sympathetic overactivity, endothelial dysfunction, and chronic volume overload), failed native kidneys, elevated FGF23 and sympathetic overactivity.
Post-transplant hypertension – associated with decreased graft survival (high systolic blood pressures) and increased mortality due to left ventricular hypertension and HFpEF.
Blood pressure measurement method could be either office BP (OBP), home BP monitoring (HBPM) or a 24-hour ambulatory BP monitoring (ABPM). A combination of OBP and HBPM is commonly used.
harmacological managements include antihypertensives like:
· Loop diuretics: Useful in control of volume overload in immediate post-transplant period, but cause hypomagnesemia and its use has been shown to be associated with increased UTI risk in first 5 years post-transplant. May be used with ACE inhibitors and ARBS in transplant renal artery stenosis.
· Thiazide diuretics: useful in patients with oedema and hypomagnesemia. Can be used in combination with CNIs (causing salt-sensitive hypertension). May cause hypercalcemia, hyperuricemia, and hyponatremia.
· Mineralocorticoid receptor antagonists: They are useful in patients with systolic dysfunction, CNI induced hypertension and proteinuria due to antiproteinuric effects and cardiovascular benefits. But their use is associated with hyperkalaemia.
· Beta blockers: most common antihypertensive used in transplant recipients. They inhibit sympathetic nervous system and decrease atherosclerotic risk (cardioprotective) but cause proteinuria, hyperkalaemia, and mask symptoms of hypoglycaemia.
· Calcium channel blockers (CCBs): Commonly used, they prevent post-transplant acute tubular injury and delayed graft function, are associated with reduced graft loss and increased GFR. The use of diltiazem is associated with elevated CNI levels. They may cause peripheral oedema, muscle weakness (when used with steroids) and gum hyperplasia.
· ACE inhibitors/ ARBs: They cause regression of LVH, are antiproteinuric and reduce occurrence of interstitial fibrosis/ tubular atrophy. But their use is associated with reduction in GFR and haematocrit. They should not be used in early post-transplant period and are useful in patients with LVH, CCF and proteinuria.
· Alpha1 antagonists: used as adjunctive drugs
· Alpha2 agonists: Control sympathetic activity. Their use is associated with weight gain, oedema and tolerance. Rebound hypertension on discontinuation take place.
· Transplant renal artery angiography and stenting: for TRAS with increasing serum creatinine and uncontrollable hypertension
· Surgical revascularization of transplant renal artery stenosis: if renal artery angioplasty is unsuccessful.
· Treatment of OSA: Weight reduction and use of BiPAP
How do you manage hypertension after kidney transplantation in your workplace?
In our centre, we try to avoid antihypertension and usually keep bp at high value. We prefer CCB over B blocker unless patient is tachycardia or AF post LRKT. ACE I and ARB will be introduce later probably after 3 months
Post-kidney transplant HTN can be defined as persistently elevated BP or normal BP with the use of antihypertensive after a successful kidney transplant. The transplant recipient’s HTN is classified as
a) Persistent HTN
b) Recovered HTN
c) Persistent normotension
d) Post-transplant HTN
Post-transplant hypertension pathophysiology and classification:
a) Immediate post-transplant period that includes peri-transplant hypervolemia, high dose steroids, rebound hypertension, and inappropriate pain control.
b) Early post-transplant period about 26-50 weeks after kidney transplant and include: medications use like calcineurin inhibitors, weight gain, transplant renal artery stenosis, and hypertensive donor kidney.
c) Late post-transplant period which includes fibroblast growth factors-23, chronic renal allograft dysfunction, and finally obstructive sleep apnea.
The management of hypertension. It includes:
a)Lifestyle modification: The non-medications involve lifestyle modifications that have to do with diet, exercise, stress reduction. Which required for all patients.
b)The pharmacological treatment of post-transplant hypertension is a long list of medications that can be used adequately control. The drugs are-
1) Diuretics
– Loop
– Thiazides
2) Calcium channel blockers
3) Beta-blockers
4) ARBs and ACEIs
5) Alpha 1 and Alpha 2 antagonists
c) Procedural or surgical interventions:
1) Native renal sympathetic denervation
2) Native nephrectomy
3) Surgical renal denervation by bilateral native nephrectomy.
4) Catheter ablative renal denervation
5) Transplant renal artery angioplasty/stenting
So, hypertension post-transplant is common and must be detected early and treatment must initiate immediately to avoid loss of the graft. The most common morbidity in these patients is cardiovascular disease and hypertension.
In my country, I usually use CCB and Beta-blockers in most hypertensive transplant patients.
Summarize this article
Hypertension (HTN) is a common co-morbidity post-transplant and its prevalence ranges from 24 to 90%.
In absence of available strong evidence, BP of less than 130/80 is a reasonable target in post-transplant population.
Post-Transplant HTN is categorized as
1. Persistent HTN
2. Recovered HTN
3. Post-Transplant HTN
Causes of Post-Transplant HTN differs across different post-transplant periods and classified as:
Immediate Post Transplant Period:
1. Peri-Transplant Hypervolemia
2. High Dose steroids: Due to arterial vascular resistance from alteration in intrinsic pressor response. Threshold dose for having HTN is 20mg of steroids.
3. Rebound Hypertension: Due to sympathetic overactivity due to abrupt discontinuation especially Clonidine and Beta-Blockers.
4. Inappropriate Pain management: Sympathetic nervous system activation and stimulation of neuro-endocrine system via HPA axis leads to pain induced hypertension
Early Post-Operative Period: Between 24 to 52 weeks post-transplant
1. Weight Gain
2. CNI: Increased Vasoconstriction, Impaired Vasodilation, sympathetic excitation, and increased Na and Cl reabsorption in DCT leading to salt sensitive HTN
3. Steroids
4. Hypertensive Donor Kidney
5. Transplant Renal artery Stenosis: accounts for 1-5% Post Transplant HTN. Generally diagnosed between 3 to 24 months post-transplant. Non-Immunological causes includes vascular damage during surgery or native vascular disease in both donor and recipient artery. Immunological causes are vascular endothelial dysfunction, immune mediated vascular endothelial injury (Diffuse stenosis). Other risk factors are CMV infection, atherosclerosis.
Late Post Transplant period:
1. Chronic Renal allograft Dysfunction
2. Fibroblast Growth Factor 23
3. OSA
Blood Pressure measurement: Home blood pressure monitoring (recording at least twice the daily average of two home blood pressure reading over a min for 4 days) and office blood pressure (mean of three non-invasive BP measurement in office) is widely used for HTN diagnosis, monitor possible white coat or masked hypertension and prescribing/adjusting antihypertensive medications
HTN Management:
Lifestyle management: Diet, exercise, and stress reduction
Pharmacological management:
1. Diuretics: Not commonly used as first line.
Loop Diuretic: Mechanism of Action (MOA): Volume control and vasodilator effect.
Thiazides: MOA is inhibition of Na-Cl cotransporter in DCT. Used in CNI induced salt sensitive HTN and hypomagnesemia
2. Mineralocorticoid Receptor Antagonist: Inhibit MCR in principal cells of CD. Antiproteinuric with Hyperkalaemia as side effect. Indicated for CNI induced Hypertension and proteinuria
3. Beta-Blockers: Favored medication in Post-Transplant HTN. Mitigation of sympathetic tone and decrease proinflammatory cytokine thereby decreasing risk of atherosclerosis and is cardio protective. SE includes proteinuria, hyperkalemia, and masking of hypoglycemic symptoms.
4. CCB: MOA, Vasodilatory effects. Preferred first line for post-transplant HTN.SE, Peripheral oedema and muscle weakness especially when used along with steroids. Dihydropyridines compete with CNI as metabolized by a CYP (Cytochrome P45)3A4 isoenzyme leads to increase in both CCB and CNI exposure. Non-Dihydropyridines CCB inhibits CYP3A4 isoenzyme and significantly increases CNI level
5. ACEI/ARB: Not the first choice in immediate and early transplant period due to known effect in decrease in GFR which will add confusion. Used later when graft function stabilizes and especially in proteinuria with LVH or congestive heart failure
6. Alpha 1 Antagonist: Adjunctive therapy and rarely as initial or single antihypertensive therapy
7. Alpha 2 Agonist: MOA, stimulates Presynaptic adrenoreceptors in CNS and suppress central sympathetic activity. Rarely used as initial/single agent
Other measures for Blood pressure control
1. Native Nephrectomy: Mainly studied in ADPKD
2. Surgical renal denervation by bilateral nephrectomy
How do you manage hypertension after kidney transplantation in your workplace?
CCB and/or Beta blockers are commonly used medication in immediate and early transplant period
Diuretics are used for volume control in immediate or early post-transplant period
Once graft function stabilizes addition or replacing ACEI/ARB for Dihydropyridine CCB and betablockers if Proteinuria or post-transplant Polycythemia
Various risk factors like Obesity, OSA to be adequately treated
Advise Lifestyle modification
Hypertension in kidney transplant patients is common with prevalence ranging from 24-90%, occurring in patients with other metabolic diseases like diabetes mellitus, obesity and hyperlipidemia. It can be categorized into 4 different categories: persistent hypertension (hypertension in both pre- and post-transplant period), recovered hypertension (correction of hypertension post-transplant), persistent normotension (no hypertension pre- and post-transplant) and post-transplant hypertension (new onset hypertension after transplant). The prevalence of persistent hypertension and post-transplant hypertension is 40% and 19% respectively.
Post-transplant hypertension can be classified as immediate-, early- (first 24 to 52 weeks) and late- (after 1 year) onset hypertension.
Risk factors for hypertension in immediate post-transplant period include volume overload (due to intravenous fluids, especially in patients with delayed graft function), use of induction agent and high dose steroids (increasing vascular resistance), increased pain (due to sympathetic overactivity), and rebound hypertension (due to sudden stoppage of beta blockers and clonidine).
Risk factors for hypertension in early post-transplant period include obesity and weight gain, calcineurin inhibitor use (due to reduced vasodilatation and sympathetic nervous system activation), steroid use (if dose more than 20 mg per day), donor hypertension (or if donor has a family history of hypertension) and transplant renal artery stenosis (due to immunological and non-immunological causes).
Hypertension in late post-transplant period is associated with chronic graft dysfunction (persistent antibody mediated rejection, Interstitial fibrosis and tubular atrophy, thrombotic microangiopathy and disease recurrence), obstructive sleep apnea (due to sympathetic overactivity, endothelial dysfunction and chronic volume overload), failed native kidneys, elevated FGF23 and sympathetic overactivity.
Post-transplant hypertension is associated with decreased graft survival (especially with high systolic blood pressures) and increased mortality (due to left ventricular hypertension and HFpEF).
Blood pressure measurement method could be either office BP (OBP), home BP monitoring (HBPM) or a 24-hour ambulatory BP monitoring (ABPM). A combination of OBP and HBPM is commonly used.
Blood pressure management in kidney transplant recipients include non-pharmacological measures (lifestyle modifications – diet, exercise, weight reduction and stress reduction), pharmacological measures , and procedural or surgical interventions.
Pharmacological managements include antihypertensives like:
a) Loop diuretics: Useful in control of volume overload in immediate post-transplant period, but cause hypomagnesemia and its use has been shown to be associated with increased UTI risk in first 5 years post-transplant. May be used with ACE inhibitors and ARBS in transplant renal artery stenosis.
b) Thiazide diuretics: useful in patients with edema and hypomagnesemia. Can be used in combination with CNIs (causing salt-sensitive hypertension). May cause hypercalcemia, hyperuricemia and hyponatremia.
c) Mineralocorticoid receptor antagonists: They are useful in patients with systolic dysfunction, CNI induced hypertension and proteinuria due to antiproteinuric effects and cardiovascular benefits. But their use is associated with hyperkalemia.
d) Beta blockers: most common antihypertensive used in transplant recipients. They inhibit sympathetic nervous system and decrease atherosclerotic risk (cardioprotective) but cause proteinuria, hyperkalemia and mask symptoms of hypoglycemia.
e) Calcium channel blockers (CCBs): Commonly used, they prevent post-transplant acute tubular injury and delayed graft function, are associated with reduced graft loss and increased GFR. The use of diltiazem is associated with elevated CNI levels. They may cause peripheral edema, muscle weakness (when used with steroids) and gum hyperplasia.
f) ACE inhibitors/ ARBs: They cause regression of LVH, are antiproteinuric and reduce occurrence of interstitial fibrosis/ tubular atrophy. But their use is associated with reduction in GFR and hematocrit. They should not be used in early post-transplant period and are useful in patients with LVH, CCF and proteinuria.
g) Alpha1 antagonists: used as adjunctive drugs
h) Alpha2 agonists: Control sympathetic activity. Their use is associated with weight gain, edema and tolerance. Rebound hypertension on discontinuation take place.
Procedures and surgical interventions: These are adopted in patients with resistant hypertension, and include-
a) Native nephrectomy: especially in patients with ADPKD
b) Native renal sympathetic denervation
c) Surgical renal denervation by bilateral native nephrectomy
d) Catheter ablative renal denervation.
e) Transplant renal artery angiography and stenting: for transplant renal artery stenosis with increasing serum creatinine and uncontrollable hypertension
f) Surgical revascularization of transplant renal artery stenosis: if renal artery angioplasty is unsuccessful.
g) Treatment of OSA: Weight reduction and use of BiPAP
There is no specific antihypertensive recommended in post-transplant hypertension treatment. The treatment should be individualized.
The management of hypertension in our workplace includes emphasis on lifestyle modification (regular exercise and diet advise). The antihypertensives used in our unit include CCBs and beta blockers. Patients on clonidine pre-transplant are continued on them post-transplant and tapered later on as per the requirements. ACE inhibitors are added in proteinuric patients, keeping an eye on the creatinine levels. ACE inhibitors/ ARBS are avoided in first 3 months. If the creatinine increases with ACE inhibitor use, we rule out possibility of transplant renal artery stenosis by renal Doppler. We have not encountered any resistant hypertension requiring surgical nephrectomy. We do not have facility of renal denervation in our setup.
This article is giving details about the approach and management of hypertension after a kidney transplant. Cardiovascular diseases pre- and post-transplant are the most common comorbidity found in all patients. It is also present in the majority of posttransplant individuals.
Since the introduction of CNI graft survival has improved but the long-term effect has been evolving. This effect is the increased risk of mortality due to cardiovascular disease and the one of interest is hypertension. Hypertension is a usual finding in the transplant population and is the most common risk factor for CVD. The overall prevalence of posttransplant hypertension has ranged from 24 to 90%.
Post-transplant HTN is defined as a persistently elevated BP or normal BP with the use of antihypertensive after a successful kidney transplant. The transplant recipient’s HTN is classified as:
1) Persistent HTN
2) Recovered HTN
3) Persistent normotension
4) Post-transplant HTN
Post-transplant hypertension pathophysiology and classification:
1) Immediate post-transplant period that includes peri-transplant hypervolemia, high dose steroids, rebound hypertension, and inappropriate pain control.
2) Early post-transplant period about 26-50 weeks after kidney transplant and include: medications use like calcineurin inhibitors, weight gain, transplant renal artery stenosis, and hypertensive donor kidney.
3) Late post-transplant period which includes fibroblast growth factors-23, chronic renal allograft dysfunction, and finally obstructive sleep apnea.
The management of hypertension. It includes:
1) Non-medications
2) Medications
The non-medications involve lifestyle modifications that have to do with dieting, exercise, avoidance of stressful events or activities, avoiding alcohol and coffee, etc.
The pharmacological treatment of post-transplant hypertension is a long list of medications that can be used adequately control. The drugs are:
1) Anti-calcium channel blockers
2) Beta-blockers
3) ARBs and ACEIs are not frequently used in transplant patients. They have their rightful specifications, especially in patients with proteinuria and erythrocytosis.
4) Antidiuretics are not generally sued but may have indications for patients with fluid overload or to challenge the graft to respond after the patient is hydrated adequately.
5) Alpha 1 antagonists like clonidine
There are other forms of treatment that can be used but are not common practice because the above measures should be able to control the BP but if not the case the following can be attempted:
1) Native renal sympathetic denervation
2) Native nephrectomy
3) Surgical renal denervation by bilateral native nephrectomy.
4) Catheter ablative renal denervation
5) Transplant renal artery angioplasty/stenting
So, hypertension post-transplant is common and must be detected early and treatment must initiate immediately to avoid loss of the graft. The most common morbidity in these patients is cardiovascular disease and hypertension falls on the top list. Therefore, to preserve the graft it must be treated.
In my country, there aren’t many kidney transplants and my experience with using them is limited but to my knowledge gain, the above common ones are what are most likely to be used to control patients’ blood pressures.
It is a study talking about pre- and post-transplant hypertension and the risk groups involved, especially patients with a history of metabolic changes (diabetes mellitus, hyperlipidemia, and obesity). Post-transplant hypertension is divided into immediate, early, and late.
Cardiovascular disease is the main cause of death in this group, especially in patients using cyclosporine. Normotensive patients before and after transplantation (persistent normotensives) and those who normalized after transplantation (recovered hypertension) have the best prognosis, while persistent hypertension (already previously) and those who started after transplantation have the worst prognosis.
There is a lot of discussion about what is the appropriate blood pressure and diastolic pressure in this patient profile, but most consider it to be < 130x80mmHg.
Immediate Post-transplant period
Early Post-transplant period
Late post-transplant period
We are aware of the high correlation between blood pressure control, renal graft function and post-transplant cardiac function. Sometimes, to obtain more reliable values, an outpatient blood pressure assessment is necessary. High differences between blood pressure values during the day suggest post-transplant hypertension and the need for treatments with lifestyle changes (diet, exercise and stress reduction), as well as the best specific pharmacological profile for each individual.
Other management for blood pressure
In our service, we provide all antihypertensive drugs in the public system, with the exception of alpha 1 antagonists. A multidisciplinary team plays a crucial role in the individualization of treatment.
Briefly summarise this article
-Overall prevalence of post-transplant HTN has ranged from 24 to 90% .
– The definition of HTN in kidney transplant recipients remains controversial, and hard outcomes related to BP levels are still limited.
– A recent 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend a target BP of <130/80 mmHg .
Immediate Post-transplant Period
Post-transplant HTN is generally a result of external factors like transplant surgery, IV fluids, and high doses of steroids.
Early Post-transplant Period
– The early post-transplant period is between 24 and 52 weeks post transplantation. Several factors contribute to HTN like weight gain,steroids ,CNI,hypertensive donor kidney,transplant renal artery stenosis.
Late Post-transplant Period
-Chronic Renal Allograft Dysfunction
Common causes of renal allograft injury include acute allograft rejection—both
acute antibody-mediated—and acute cellular rejection. allograft (19).
-Fibroblast Growth Factor (FGF) 23.
-Obstructive Sleep Apnea .
-increased sympathetic activity .
-Several studies have demonstrated an association between post-transplant
HTN and renal allograft failure .
Management of HTN:
–Non-pharmacologic interventions :
-diet, exercise, and stress reduction, should always be part of treatment of HTN.
– Additionally, other interventions specific to certain etiologies of resistant HTN, such as transplant renal artery angioplasty ± stenting and treatment for OSA,
should be implemented.
-Renal sympathetic denervation of the native kidneys either by bilateral native nephrectomy or catheter ablation is also treatment option for resistant HTN in this population .
PHARMACOLOGICAL MANAGEMENTS
-Beta-blockers were the most common antihypertensive medication used in this cohort followed by calcium channel blockers.
-Uses of ACEI, diuretics, and alpha blockers were about the same.
-ARB therapy was utilized least.
– ACEI and ARB are generally held following a transplant. An alpha2 agonist like clonidine, however, may need to be continued during peritransplant
period to avoid rebound HTN.
-Diuretics are not commonly used as the first line antihypertensive medication in kidney transplant recipients. They may cause volume depletion, electrolyte disturbances, and worsening renal allograft function.
– Loop diuretic use has been associated with increased risk of UTI during the first 5 years after kidney transplantation..
-Thiazides may be considered for kidney transplant recipients with CNI-induced salt-sensitive HTN and hypomagnesemia.
-MCRA may be a new option for BP control in individual with CNI-induced HTN
and proteinuria.
– The beta blocker has additive effect on ACEI or ARB with greater survival
in kidney transplant patients on this combination compared to those who received either medication alone or neither.
-The vasoconstrictive effect of CNIs leads to post-transplant HTN , calcium channel blockers are thought to be an appropriate agent for post-transplant HTN. Theoretically their vasodilatory effect can counteract the vasoconstrictive effect ofCNIs and improve BP control .
-Calcium channel blockers also prevent post-transplant acute tubular injury (ATI)
or DGF.
-ACEIs and ARBs can lead to regression of LVH in kidney transplant recipients but no an improvement in all-cause mortality .
-ACEIs and ARBs are generally not the drugs of choice during the immediate
and early post-transplant periods.
-Alpha1-antagonists are rarely used as the initial or as a single antihypertensive agent in kidney transplant recipients.
– Alpha1-antagonist may have a role as an adjunctive therapy rather than first line antihypertensive agent in transplant recipients.
– Clonidine is currently the most commonly used alpha2 agonist. When used
as monotherapy, methyldopa is associated with antihypertensive tolerance, edema, and weight gain. Clonidine is also associated with weight gain and progressive resistance with continued use.
-Clonidine is rarely used as a single antihypertensive agent following kidney transplantation.
OTHER MANAGEMENT FOR BLOOD PRESSURE
Native Nephrectomy
Native Renal Sympathetic Denervation
Surgical Renal Denervation by Bilateral Native Nephrectomy
Catheter Ablative Renal Denervation
How do you manage hypertension after kidney transplantation in your workplace?
In the first months ,commonly we used CCB or BB…later we add ACEi or ARBs.
Briefly summarise this article
DEFINITION OF POST-TRANSPLANT HYPERTENSION
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation.
Kidney transplant recipients can be categorized, based upon HTN, into four groups:
· persistent HTN,
· recovered HTN
· persistent normotension
· post-transplant HTN
The European Society of Hypertension and the European Society of Cardiology guidelines defined isolated systolic in the general population as HTN as SBP>140 and DBP <90 mmHg.
PATHOGENESISOFPOST-TRANSPLANT HYPERTENSION
Immediate Post-transplant Period
· Peri-transplant Hypervolemia
· High-Dose Steroids
· Rebound Hypertension
· Inappropriate Pain Management
Early post-transplantation
· Weight Gain
· Calcineurin inhibitors
· Steroid
· Hypertensive donor kidney
· Transplant renal artery stenosis
Late post-transplantation
· Chronic renal allograft dysfunction
· Fibroblast growth factor 23
· Obstructive sleep apnea
· Failed native kidneys
· Sympathetic overactivity
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
Very low pretransplant BP (<110 / 50 mmHg) associated with a decrease in renal allograft loss. On the other hand, post-transplant elevated BP is associated with poorer renal allograft and patient outcomes.
Cardiovascular Outcomes-Related to Post-transplant Hypertension
Kidney transplant recipients with (LVH) or HFpEF have increased morbidity and mortality and are at high risk for cardiac-related events.
BLOOD PRESSURE MEASUREMENT
Reliable BP measurement should be mandatory in clinical practice and can be standardized with the following definitions:
· Office blood pressure (OBP) the mean of three non-invasive BP measurements
· Home blood pressure monitoring (HBPM) recording at least twice the daily average of two home blood pressure readings over a minimum of 4 days
· 24-h ambulatory blood pressure monitoring (24-h ABPM)
Although HBPM is available, better correlated to 24-h ABPM, and superior to OBP when predicting hard outcomes, HBPM is used in conjunction with OBP for KT patients to minimize misclassification of HTN diagnosis, monitor possible white coat or masked HTN, and adjust antihypertensive medications.
BLOOD PRESSURE MANAGEMENT
Non-pharmacologic interventions, such as diet, exercise, and stress reduction, should always be part of treatment of HTN.
Pharmacologic interventions by using the antihypertensive medications remain the cornerstone of BP control.
Procedural or Surgical interventions for certain cases of resistant HTN.
BLOOD PRESSURE CONTROL DURING PERI-TRANSPLANT PERIOD
Antihypertensive Medications
· Diuretics (Loop Diuretics, Thiazides, Mineralocorticoid Receptor Antagonists)
· Beta-Blockers
· Calcium Channel Blockers
· Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor Blockers (ARB)
· Alpha1-Antagonists
· Alpha2 Agonists
OTHER MANAGEMENT FOR BLOOD PRESSURE
· Native Nephrectomy
In ESRD patients with resistant HTN, defined as uncontrolled BP with at least three antihypertensive medications of which one is a diuretic, secondary HTN should be considered.
· Native Renal Sympathetic Denervation
Sympathetic over activity from failed native kidneys is another mechanism that leads to resistant HTN. The effect of RDN on BP control was established
· Surgical Renal Denervation by Bilateral Native Nephrectomy
· Catheter Ablative Renal Denervation
How do you manage hypertension after kidney transplantation in your workplace?
We usually follow similar scheme as outlined in the article, diuretics mainly loop are used in the immediate post-renal transplant for volume control if required. Otherwise, the patient is kept on Ca channel blockers with/out Beta blockers for controlling BP.
We usually avoid ACE-I/ARBs until 3 months post op to provide ant-proteinuric effect if indicated.
Of course, emphasis on healthy lifestyle and salt restriction as well.
Resistant cases should be investigated fully with referral to endocrinology if warranted.
Hypertension in the pre- and post-transplant period carries high risk of cardiovascular complications.
The pathogenesis of hypertension in renal transplant recipients is multifactorial including immunological and non-immunological causes. Prevalence of post-transplant HTN has ranged from 24 to 90%.
There is no agreement on the definition of hypertension between European and American societies in normal population, and so that in regards to transplant population. BP ≥130/80 mmHg may be a reasonable definition for HTN in renal transplant recipients.
In kidney transplant recipients HTN is classified into 4 categories:
Persistent HTN
Recovered HTN
Persistent normotension
Post-transplant HTN
Pathogenesis of post-transplant hypertension
1- Immediate post-transplant is hypertension that occurred in the post-operative period while patient is still hospitalized. It is usually driven by peri-transplant hypervolemia, the use of high dose steroids during induction, inappropriate pain management and rebound hypertension.
2- Early Post-transplant hypertension is defined as hypertension that occur in the period between 24 and 52 weeks post-transplantation
Development of hypertension in this period is attributed to weight gain (with resolution of uremia, patients have better appetite which is also increased by steroid use). CNI as a mainstay therapy for maintenance immunosuppression is a well-established cause of hypertension. Steroids are also common cause of hypertension by fluid retention and vasoconstriction. One should be also aware of graft related causes of hypertension that include hypertensive donor kidney and Transplant Renal Artery Stenosis (TRAS).
3- Late Post-transplant Period: In addition to factors that contribute to the development of hypertension in the early post-transplant period, additional factors may contribute to HTN in the late post-transplant period.
These include: Chronic Renal Allograft Dysfunction, altered levels of Fibroblast Growth Factor (FGF) 23 and Obstructive Sleep Apnea
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
– Very low pretransplant SBP (<110 mmHg) and DBP (<50 mmHg) are associated with a decrease in renal allograft loss
– In the post-transplant period, elevated BP is associated with poorer renal allograft and patient outcomes. Several studies have demonstrated an association between post-transplant HTN and renal allograft failure.
BP measurement is achieved with 3 different approaches:
1- Office blood pressure (OBP): the mean of 3 non-invasive BP measurements
2- Home blood pressure monitoring (HBPM): measurement at least twice, the daily average of two home BP readings over at least 4 days
3- 24-h ambulatory blood pressure monitoring (24-h ABPM): 24-h ABPM is the gold standard for the diagnosis of white coat and masked HTN
Hypertension management
Treatment is divided into medical and surgical, based on the underlying causes. Medical treatment is further subdivided into pharmacological and non-pharmacological.
Hypertension is one of the most common cardiovascular comorbidities along with other metabolic diseases.
Post kidney transplant HTN can be defined as a persistently elevated BP or normotension with the use of antihypertensive medication after successful kidney transplantation.
In this reveiw , post kidney transplation HTN refers to persistent and de novo post transplant HTN.
Causes:
Immediate post transplant period:
Early post transplant period:
This means HTN in between 24 to 52 weeks of post transplantation. Causes are:
1.Weight gain : Positive fluid intake from intra and post operative iv fluids is associated with post transplant HTN.
2.Calcineurin inhibitors: Both increased vasoconstriction and impaired vasodilation. Increased renal sodium transport handling is another cause.
3.steroids
4.Hypertensive donor kidney
5.Transplant renal artery stenosis
Late post transplant period:
Blood pressure measurement:
Office blood pressure
Home measured blood pressure monitoring
24 hour ambulatory blood pressure monitoring
Mnagement
Non pharmacologic:
Diet
Exercise
Stress reduction
Pharmacologic therapy:
Diuretics
Calcium channel blockers
Beta blockers
Renin angiotensin aldosteron system blocker
Alpha1 antagonist
ALPHA 2 AGONIST
Choices of medications depends upon patients characteristics, tolerability, medications side effects
Surgical interventions
Transplant renal; artery angioplasty with or without stenting
CPAP
Bilateral native vnephrectomy
Native renal dennervation
DEFINITION OF POST-TRANSPLANT HYPERTENSION
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation.
But what is a normal BP level?
We can categorize kidney transplant recipients into four groups:
guidelines defined isolated systolic HTN in the general population as SBP 140 and DBP <90 mmHg . This is the most common phenotype of HTN in elderly patients
PATHOGENESISOFPOST-TRANSPLANT HYPERTENSION .
2. Early post-transplantation
Cardiovascular Outcomes-Related to Post-transplant Hypertension
HTN is one of the most important risk factors for heart failure, particularly heart failure with preserved ejection fraction (HFpEF) .
Kidney transplant recipients with (LVH) or HFpEF have increased morbidity and mortality and are at high risk for cardiac-related events
BLOOD PRESSURE MEASUREMENT
Physiological decreases in nocturnal BP further classifies patients into
decrease in nocturnal reduction in SBP was associated with a lower renal allograft function.
A 24-h ABPM can address and assist with the common misclassification of HTN diagnosed traditionally by OBP or HBPM.
BLOODPRESSURECONTROLDURING PERI-TRANSPLANT PERIOD Antihypertensive Medications
Diuretics
Loop Diuretics
Thiazides
Mineralocorticoid Receptor Antagonists
Beta-Blockers
Calcium Channel Blockers
Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor Blockers (ARB)
Alpha1-Antagonists
Alpha2 Agonists
OTHER MANAGEMENT FOR BLOOD PRESSURE
In ESRD secondary to ADPKD, the mechanism of HTN from failed kidneys is related to intrarenal renin instead of systemic renin .
In kidney transplantation, the presence of failed native kidneys is associated with post-transplant resistant HTN.
ACEIs and native nephrectomy may need to be considered.
sympathetic over activity from failed native kidneys is another mechanism that leads to resistant HTN.
The effect of RDN on BP control was established
Complete RDN can be performed by bilateral native nephrectomy
Although native nephrectomy can improve posttransplant HTN, both pre- and post-transplant native nephrectomy can lead to surgical complications, which can cause impaired renal allograft function.
complete RDN by bilateral native nephrectomy in kidney transplant recipients is invasive and carries a risk of additional operation, it should be reserved for selected patients.
In our medical center
Immediately after transplantation, especially when the patient has Hypervolemia we use diuretics (Furosemide)
Persistent hypertension in the early post-transplant period we use CCB
After 3 months we use ACE inhibitor or ARBs for those who have proteinuria
This article review talk about hypertension in posttransplant patients cause greater incidence of hypertension after transplantation and outcomes after kidney transplantation and try to give a good defenetion of hypertension after transplantation.
The best defenetion by amirecan college of heart disease a blood pressure more than 130/80 is a good defenetion.
Type of hypertension is also mention and divided to four majour types :
1_persistant hypertension
2_recovered htn.
3_persistant normotensive.
4-post-transplant hypertension.
Pathogenesis ,:
Immediate:
because of iv fluids
Induction medication and steroids.
Rebound hypertension
Inadequate pain controll.
Early:
Weight gain.
Cn ihibitors
Renal artery stenosis
Late:
Chronic allograft dysfunction.
Fgf 23
Obstructiv sleep apnea.
Symptomatic overactivity.
Blood pressure management.
Divided to pharmacological and non-pharmacologic
Exercise,diet, stress reduction
Drug treatment :
Depend on the patient age and characteristic, tolerance, and medication side effect.
1- Duiretic : especially loop Duiretic better for volume control .
Furosemide is the most common used .
Its use is individually
Thiazide : uncommonly use to avoid its metabolic effects.
Maybe beneficial in cn inhibitors hypertension and decrease hyperkalemia
.
Mineral corticosteroids antagonist:
May have cv benefits and decresse protienurea.
Hyperkalemia restrict its use.
Beta blockers:
Provides survival benefits intransplanted patient but caus metabolic effect (hyperkalemia _protienurea- masking hypoglycemia)
Calcium channel blockers:
It is an appropriate choice for posttransplant patients.
Vasodilation effect against cu inhibitors vasoconstriction.
Prevent atn in some study
So it is a preferred agent in transplanted patients.
Pereferal edema ,drug to drug reactions shoud be in consideration.
Angiotensin converting enzyme inhibitors
(Acei -Arbs):
The most important effect is decreasing protienurea.
Also benefit in reducing interstitial fibrosis and tubular atrophy and lvh patients
However ,they are not the drug of choice in early and immediately transplant because they are known to cause decrease in eGFR .
Alpha1 antagonists:
It is rarley used cause .
Alpha 2 agoonists :
Centrally action
Not preferred agents
In conclusion :
Beta blockers and calcium channel blockers are the main therapy for transplanted patient.
Other nopharmacological treatment are available
Catheter ablative renal denervation and syrgical renal denervation by bilaterally nephroctomy .
How do you managment hypertension in your workplace ?
As this article we mainly depend on the tow agents
Calcium chanel blockers and betablockers and use Duiretic as nedded for volume oveload patient
Some patiens may have specific situation make us use another agents (heart failure _ protienurea)so we treat these kind of patients as appropriate.
# Briefly summarise this article
# EPIDEMIOLOGY OF POST-TRANSPLANT HTN
*The prevalence of post-transplant HTN has been increased over time, maybe related to the introduction of cyclosporine (CsA). * Overall prevalence of post-transplant HTN has ranged from 24 to 90%.
# DEFINITION OF POST-TRANSPLANT HTN
*Defined as a persistently elevated BP or norm tension with use of antihypertensive medications after successful kidney transplantation, however, different studies have defined post transplant HTN with different cutoff levels for systolic and diastolic blood pressure and different requirements for the use of antihypertensive medications.
* Kidney transplant recipients classified into 4 groups:
1)Persistent HTN (occurs in patients with HTN both in the pre- and post transplant periods 40%)
2)Recovered HTN (only during the pre- but not the post-transplant period 28%)
3)Persistent norm tensions (have no history of HTN preceding transplant and remain normotensive post-transplant 13%)
4)Post-transplant HTN (requires developing de novo HTN after kidney transplant 19%).
*Isolated HTN( systolic and diastolic) occur after KT.
*The European Society of Hypertension and the European Society of Cardiology guidelines defined isolated systolic HTN as SBP>140 and DBP <90 mmHg, most common HTN in elderly patients.
The pathogenesis involves in both intrinsic alterations resulting from normal aging process accompanied
by development of modifiable risk factors leading to increased arterial stiffness
*Diastolic HTN is defined as DBP of >90 mmHg, with a SBP <140 mmHg, and is more common in younger with higher (BMI).
*A recent 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines
recommend a target BP of <130/80 mmHg. Until there is stronger evidence of an association between BP level and outcomes in kidney transplant recipients, a BP >130/80 mmHg may be a reasonable definition for HTN in this population.
# PATHOGENESIS OF POST-TRANSPLANT HTN
# Immediate post transplantation
*Peri transplant hypervolemia
*Induction immunosuppressive medications
*Rebound hypertension
*Inadequate pain control
# Early post transplantation: (It is time between 24 and 52 weeks post-transplantation).
*Weight gain (Between 6- and 12-months post-transplantation)
*Calcineurin inhibitors(The prevalence of HTN in KT is between 70 and 90%, which is greater than the pre-CNI era of 40–50%. There are two main mechanism of CNI-induced post-transplant HTN resulting from interfering vascular tone and renal sodium transport handling.
*Steroids( may result from alterations in intrinsic pressor response leading to arterial vascular resistance)
*Hypertensive donor kidney
*Transplant renal artery stenosis (TRAS)
May occur at any time after KT but is generally diagnosed between 3 and 24
months post transplantation. Unlike (RAS) in non-transplant patients, pathogenesis of TRAS is
complex and involve:
1) Non-immunological factors include vascular damage at the time of surgical anastomosis between the donor renal artery and recipient artery as well as the presence of native vascular diseases in both donor and recipient arteries
2) Immunological factors leading to vascular endothelial dysfunction can cause
TRAS.
3) Cytomegalovirus (CMV) infection
*Three therapeutic options for TRAS are pharmacological therapy alone or pharmacologic therapy in addition to renal artery angioplasty with stenting or surgical revascularization.
*For pharmacological therapy, ACEI or ARB plus diuretics are effective regimen for BP control, but it is limited by reducing the renal function. Statins and acetylsalicylic acid may also be part of pharmacological therapy.
*Pharmacological therapy and angioplasty is preferred procedure when TRAS is recent, linear, and distal.
*Surgical revascularization is performed primarily in kinking and proximal TR
# Late post transplantation
*Chronic renal allograft dysfunction
*Fibroblast growth factor 23
*Obstructive sleep apnea
*Failed native kidneys
*Sympathetic over activity
# OUTCOMES OF HTN POST KT
* Very low pretransplant BP (<110 / 50 mmHg) associated with a decrease in renal allograft loss.
*Post-transplant elevated BP is associated with poorer renal allograft and patient outcomes
*HTN increase the of heart failure, particularly heart failure with preserved ejection fraction (HFpEF), (LVH) and so increased morbidity and mortality PKT.
*The cardio-renal dysfunction can result from salt and volume overload
# BLOOD PRESSURE MEASUREMENT
*Reliable BP measurement should be mandatory in clinical practice and can be standardized with the following definitions
1) Office blood pressure (OBP) the mean of three non-invasive BP measurements
2) Home blood pressure monitoring (HBPM) recording at least twice the daily average of two home blood pressure readings over aminimum of 4 days
3)24-h ambulatory blood pressure monitoring (24-h ABPM) which provides the average of both day and night BP readings
*HBPM is available, better correlated to 24-h ABPM, and superior to OBP when predicting hard outcomes, the used of HBPM in conjunction with OBP for KT patients to minimize misclassification of HTN diagnosis, monitor possible white coat or masked HTN, and adjust antihypertensive medications.
# BLOOD PRESSURE MANAGEMENT
* Non-pharmacologic interventions, such as diet, exercise, and stress reduction, should always be part of treatment of HTN.
* Pharmacologic interventions by using the antihypertensive medications remain the cornerstone of BP control.
*Surgical interventions
# PHARMACOLOGICAL MANAGEMENTS use of Antihypertensive Medications
*Diuretics
Not commonly used as the first line antihypertensive medication in KT recipients, due to volume depletion, electrolyte disturbances, and worsening renal allograft function, they are indicated in the peri transplant period.
*Loop Diuretics
Volume control is the indication for loop diuretics in KT recipients, during immediate and early post-transplant periods. Associated with increased risk of UTI during the first 5 years after K.
Furosemide is the most commonly used loop diuretic.
*Thiazides
Commonly used antihypertensives, but uncommon in KT recipients because of
Their S/E which include hyperglycemia, hyperuricemia, hypercalcemia, and Hyponatremia, theoretically control CNI-induced HTN. Since CNI-induced HTN is salt sensitive
*Mineralocorticoid Receptor Antagonists
Have CV benefits and antiproteinuric effect but are not used antihypertensives in KT recipients, especially those with impaired renal allograft
*Beta-Blockers
The cardioprotective effects and survival benefit of beta-blockers make them a favored medication in the general and ESRD populations
In KT recipients, has additive effect on ACEI or ARB with greater survival on this combination compared to those who received either medication alone or neither
Beta-blockers decrease proinflammatory cytokines, which are known to increase the risk for atherosclerosis.
The S/E are proteinuria, hyperkalemia, and masking of hypoglycemic symptoms.
*Calcium Channel Blockers
Can result in vascular vasodilation, since the vasoconstrictive effect of CNIs leads to post-transplant
HTN, it is suitable agent for post-transplant HTN. Also prevent post-transplant acute tubular injury (ATI) or DGF.
Although it provide better renal allograft function, several studies showed no difference in terms of BP control when using verapamil compared to enalapril or doxazosin
Calcium channel blockers
The S/E are peripheral edema and muscle weakness especially when used in combination with steroids. Gum hyperplasia when used with CsA. Although dihydropyridine calcium channel blockers do not inhibit the cytochrome P450 (CYP) 3A4 isoenzyme, leads to increase in both calcium channel blocker and CNI
exposure levels.
*Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor
Blockers (ARB)
ACEIs and ARBs are antihypertensive agents with known antiproteinuric effect, eGFR, and hematocrit, they can lead to regression of LVH in kidney transplant recipients, but they are not the drugs of choice during the immediate and early post-transplant periods, because they are decrease GFR. This S/E is reversible, but it leads to a confusion early on differentiating their role from other causes of renal allograft dysfunction and may lead to unnecessary invasive investigation, e.g. biopsy.
*Alpha1-Antagonists
Rarely used as the initial or single antihypertensive in KT recipients, they reduce BP by decreasing peripheral vasoconstriction
Alpha1-antagonist may have a role as an adjunctive therapy rather than first line antihypertensive agent
in transplant recipients.
*Alpha2 Agonists
Centrally acting work on presynaptic alpha2 adrenoceptors in the CNS and suppress central sympathetic activity and lowers BP.
Two of the oldest alpha2 agonists, methyldopa and clonidine, have long been used for BP control. methyldopa when used as monotherapy, is associated with antihypertensive tolerance, edema, and weight gain.
Clonidine is also associated with weight gain and progressive resistance and is rarely used as a single antihypertensive agent following KT due to rebound HTN after discontinuation
# In summary, there is no drug of choice for BP control after KT. Several factors are involved in selecting the appropriate antihypertensive medications include immunologic and non-immunologic factors as well as the time after KT. Bet ablockers and calcium channel blockers are the most frequently
used combination in KT recipients.
Beta-blockers provide a cardioprotective for CAD.
Calciumchannel blockers have vasodilatory effect that counteracts the vasoconstrictive effect of CNIs ACEIs and ARBs, are not routinely used in KT during the early post-transplant period when baseline renal allograft function is not well-established can be considered when there is a specific indication such as proteinuria and posttransplant erythrocytosis.
Elevated serum creatinine from ACEI or ARB therapy, although reversible, is the main reason
they are avoid.
Diuretics are not the first line for BP control in kidney transplant recipients. It may be used for volume control at immediate or early post-transplant.
OTHER MANAGEMENT FOR BLOOD PRESSURE
*Native Nephrectomy
In ESRD patients with resistant HTN, defined as uncontrolled BP with at least three antihypertensive medications of which one is a diuretic, secondary HTN should be considered.
*Native Renal Sympathetic Denervation
Done in sympathetic overactivity from failed native kidneys is another mechanism that leads to resistant HTN
The effect of RDN on BP control was established
*Surgical Renal Denervation by Bilateral Native Nephrectomy
*Catheter Ablative Renal Denervation
# How do you manage hypertension after kidney transplantation in your work place?
For measurement of blood pressure we use office BP and home BP monitoring, in very rare cases we may need 24-h ABPM
Non-pharmacologic management like control the diet, exercise, and stress reduction should be done for all patients.
Calcium Channel Blockers and or Beta-Blockers are used as first-line during the immediate or early post-transplant period.
In some cases one or more additional drug/ drugs can be added like Alpha2 Agonists ( methyldopa), Doxazosin.
Diuretics may be used for volume control at immediate or early post-transplant.
ACEI or ARB should be stopped before one week of transplantation and reintroduce only after 3 monthes when there is indication.
Introduction:
· Cardiovascular diseases are the leading cause of mortality in post-transplant patients, and Hypertension is one of the most common cardiovascular co-morbidities (prevalence ranged from 24 to 90%) it’s important to diagnosed and properly managed.
· Its define as a persistently elevated BP or normotension with use of antihypertensive medications *as SBP ≥140 and DBP <90 mmHg in most of the society guidelines . and divided to 4 types depending on BP status pre transplant: persistent HTN, recovered HTN, persistent normotension, and post-transplant HTN.
Depending on timing to transplantation factors contributed to raise in blood pressure vary:
Immediate Post-Transplant Period:
ü Peri-transplant hypervolemia
ü Induction immunosuppressive medications
ü Rebound hypertension
ü Inadequate pain control
Early Post-Transplant Period: define as between 24 and 52 weeks’ post-transplantation:
ü Weight gain
ü Calcineurin inhibitors
ü Steroids
ü Hypertensive donor kidney
ü Transplant renal artery stenosis
Late Post-Transplant Period:
ü Factors of early post-transplant above
ü Chronic renal allograft dysfunction
ü Fibroblast growth factor 23
ü Obstructive sleep apnea
ü Failed native kidneys
ü Sympathetic overactivity
These factors might also be classified as
Immunological factors including: DGF, Immunosuppression (CNI, Corticosteroids), Acute or chronic rejection
Non-immunological Factors:
ü Surgical related: Intraoperative volume administration, Transplant renal artery stenosis
ü related to the Donor: Hypertensive kidney, Family history of HTN in donor, Transplant renal artery stenosis
ü related to the Recipient: Pre-existing HTN, Renal allograft dysfunction, Dietary sodium intake, Metabolic syndrome, TRAS, OSA, Failed native kidneys, Sympathetic over activity
Blood Pressure Management: target ≤130/80
Non-pharmacologic:
ü Dietary control
ü Life style modification: exercise, and stress reduction
Pharmacological: antihypertensive medications:
Diuretics : not the first line
Loop ,Thiazide:
· Used for volume control
· May use with ACEI or ARB in TRAS
· Renal sodium excretion defect in CsA-induced HTN
CCB calcium channel blocker
· Afferent arteriolar vasodilatation
· May improve renal allograft function and lower DGF but inconclusive
*Non-dipyridamole CCB is CYP450 inhibitor and increases CNI level
ACEI/ARB
· Anti-proteinuric
· Cardioprotection
· May use with diuretic in TRAS
Beta-blockers: cardioprotection
Mineralocorticoid receptor antagonists:
– Systolic dysfunction – Safe with using ACEI and ARB but increase hyperkalaemia
Alpha1 antagonist :Generally, not the first line
Alpha2 agonist
· Lower plasma renin activity that modulated renal vascular resistance and lower MAP.
· No change in GFR and effective renal plasma flow.
Other Interventions: for resistant HTN:
Specific to certain etiologies, such as Transplant Renal Artery Angioplasty ± Stenting
Bilateral Native Nephrectomy
Renal sympathetic denervation
During perioperative time: close monitor to BP, with adequate pain control to avoid low or high reading. if needed parenteral antihypertensive medication can be used (labetalol example)
At hospital discharge advice about weight control, salt low, and general dietary plan with nutritionist
Follow up visit and BP regular measuring to diagnose any HTN early.
When BP reading is high: looking for drug level, assessment of graft function, volume status and all other possible factors
Medication: CCB is commonly used as first line, we avoid ACEi specially at early post-transplant period so not to be confused if creatinine readings start to rise.
Hypertension is one of the most common cardiovascular co-morbidities after successful kidney transplantation.
The pathogenesis of post-transplant hypertension is complex and is a result of the interplay between immunological and non-immunological factors,which can be divided intoimmediate, early, and late post-transplant periods.
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation.
it can be divided into four groups: persistent HTN, recovered HTN, persistent normotension, and post-transplant HTN. Persistent HTN occurs in patients with HTN both in the pre- and posttransplant periods, whereas patients with recovered HTN have HTN only during the pre- but not the post-transplant period. Persistent normotensive patients have no history of HTN preceding transplant and remain normotensive post-transplant. Post-transplant HTN requires developing de novo HTN after kidney transplant
The European Society of Hypertension and the European Society of Cardiology guidelines defined isolated systolic HTN in the general population as SBP ≥ 140 and DBP <90 mmHg , new BP guidelines and re-defined HTN for the general population as systolic blood pressure (SBP) >130 or DBP >80 mmHg
main causes of of post transplant HTN are classified into :
immediate post transplant
early post transplantation
late post transplantation
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
Pre-transplant BP is associated with renal allograft and patient survival outcomes after kidney transplantation. Very low pretransplant SBP (<110 mmHg) and DBP (<50 mmHg) are associated with a decrease in renal allograft loss. Specifically during dialysis lower pre- and post-dialysis DBP are associated with better patient survival post-transplantation
Several studies have demonstrated an association between post-transplant HTN and renal allograft failure.
BLOOD PRESSURE MANAGEMENT
Non-pharmacologic interventions, such as diet, exercise, and stress reduction, should always be part of treatment of HTN but pharmacological intervention remains the cornerstone of BP control in this population. Additionally, other interventions specific to certain etiologies of resistant HTN, such as transplant renal artery angioplasty ± stenting and treatment for OSA, should be implemented. Renal sympathetic denervation of the native kidneys either by bilateral native nephrectomy or catheter ablation is also treatment option for resistant HTN in this population .
there is no drug of choice for BP control after kidney transplantation. Several factors are involved in selecting the appropriate antihypertensive medications include immunologic and non-immunologic factors as well as the time after kidney transplantation.
Different from the non-transplant CKD population, betablockers and calcium channel blockers are the most frequently used combination in kidney transplant recipients. Beta-blockers provide a cardioprotective effect for kidney transplant patients, who likely have underlying CAD.Calcium channel blockers have vasodilatory effect that counteracts the vasoconstrictive effect of CNIs .
Similarly to ACEIs and ARBs, diuretics are not generally used as the first line for BP control in kidney transplant recipients. It may be used for volume control at immediate or early post-transplant.
Management for OSA and interventions for resistant HTN, such as transplant renal artery angioplasty ± stenting, bilateral native nephrectomy, and native RDN, remain options for resistant HTN in selected kidney transplant recipients. There is no conclusive BP target for this population and therapy targets need to be individualized.
Hypertension is one of the most common cardiovascular co-morbidities after
successful kidney transplantation
The pathogenesis of post-transplant hypertension is complex and is a result of the interplay between immunological and non-immunological factors
Post-transplant hypertension can be divided into immediate, early, and late post-transplant periods.
Post-kidney transplant HTN can be defined as a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation.
the presence or absence of HTN during the pre-kidney transplant period
may further categorize kidney transplant recipients into
four groups:
PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION :
1- Immediate Post-transplant Period
2- Early Post-transplant Period ( 26–50 weeks after kidney transplantation )
3- Late Post-transplant Period
BLOOD PRESSURE MANAGEMENT
there is no drug of choice for BP control after kidney transplantation. Several factors are involved in selecting the appropriate antihypertensive medications include
immunologic and non-immunologic factors as well as the time
after kidney transplantation.
Different from the non-transplant CKD population, betablockers and calcium channel blockers are the most frequently used combination in kidney transplant recipients. ACEIs and ARBs, on the other hand, are not routinely used antihypertensive medications in kidney transplant recipients. They can, however, be considered when
there is a specific indication for their use, such as proteinuria and posttransplant erythrocytosis. .
diuretics are not generally used as the first line for BP control in kidney transplant recipients. It may be used for volume control at immediate or
early post-transplant.
1- Native Nephrectomy
2- Native Renal Sympathetic Denervation
3- Surgical Renal Denervation by Bilateral Native Nephrectomy
4- Catheter Ablative Renal Denervation
EPIDEMIOLOGY OF POST-TRANSPLANT HYPERTENSION
Depending on the definition and methods of blood pressure (BP) measurement utilized
has ranged from 24 to 90%
DEFINITION OF POST-TRANSPLANT HYPERTENSION
a persistently elevated BP or normotension with use of antihypertensive medications after successful kidney transplantation.
kidney transplant recipients categorized into four groups:
persistent HTN
recovered HTN
persistent normotension
post-transplant HTN.
The European Society of Hypertension and the European Society of Cardiology guidelines defined isolated systolic HTN in the general population as SBP ≥140 and DBP <90 mmHg
diastolic HTN is defined as DBP of ≥90 mmHg, with a SBP <140 mmHg, and is more common in younger
recent 2017 (ACC/AHA) guidelines recommend a target BP of <130/80 mmHg
PATHOGENESIS OF POST-TRANSPLANT HYPERTENSION
● Immediate Post-transplant Period :
* Peri-transplant Hypervolemia
* High-Dose Steroids
* Rebound Hypertension
* Inappropriate Pain Management
● Early Post-transplant Period
* Weight Gain
* Calcineurin Inhibitors
* Steroids
* Hypertensive Donor Kidney
* Transplant Renal Artery Stenosis (TRAS)
● Late Post-transplant Period
* Chronic Renal Allograft Dysfunction
* Fibroblast Growth Factor (FGF) 23
* Obstructive Sleep Apnea
* Failed native kidney
* Sympathetic overactivity
Pathogenesis of post-kidney transplant hypertension is divided into
■ immunological factors
▪︎ Renal allograft dys function ( DGF , rejection )
▪︎ Immunosupression ( CNi , steroid )
■ Non immunological factors
▪︎ Donor ( hypertensive kidney , TRAS , family history of hypertension )
▪︎ Surgical ( intraoperative volume administration , TRAS )
▪︎ Recipiant ( pre-existing HTN , renal allograft dysfunction , diatery sodum intake , metabolic syndroms , OSA , TRAS , failed native kidney , sympathic overactivity )
OUTCOMES OF HYPERTENSION AFTER KIDNEY TRANSPLANTATION
during dialysis lower pre- and post-dialysis DBP are associated with better patient survival post-transplantation
During the post-transplant period, elevated BP is associated with poorer renal allograft and patient outcomes
Cardiovascular Outcomes-Related to Post-transplant Hypertension
HTN is a risk factors for heart failure with preserved EF
Uncontrolled HTN after kidney transplantation leads to structural damage to both the renal allograft and heart eventually resulting in decreased renal and cardiac functions.
BLOOD PRESSURE MEASUREMENT
BP standardized with the following definitions:
Office BP :
the mean of three non-invasive BP measurements
HBPM :
recording at least twice the daily average of two home blood pressure readings over a minimum of 4 days
24-h ABPM
wearing an electronic blood pressure measurement device to record and averages multiple readings over a 24 h period
Physiological decreases in nocturnal BP further classifies patients into dippers, non-dippers, and reverse dippers.
There is a significant decrease in the nocturnal reduction SBP after kidney transplantation and was associated with a lower renal allograft function.
Although a 24-h ABPM can discover white coat and masked HTN, OBP and HBPM are more commonly used in clinical practice.
There is a higher correlation between a 24-h ABPM and HBPM than 24-h ABPM and OBP and nighttime elevation in SBP exhibited decreased graft function
association
An elevated 24-h average SBP was significantly associated with graft loss, cardiovascular events and death over a 5-year follow-up period in kidney transplant recipients with diabetes, lower eGFR, proteinuria, young age, and female
BLOOD PRESSURE MANAGEMENT
Non-pharmacologic interventions, such as diet, exercise, and stress reduction
pharmacological intervention remains the cornerstone of BP control in this population.
** Diuretics are not commonly used as the first line antihypertensive medication in kidney transplant recipients
Volume control rather than BP control is the indication for loop diuretics in kidney transplant recipients
Thiazides may be considered for kidney transplant recipients with CNI-induced salt-sensitive HTN and hypomagnesemia.
metabolic side effects which include hyperglycemia, hyperuricemia, hypercalcemia, and hyponatremia
Mineralocorticoid Receptor Antagonists MCRA may be a new option for BP control in individual with CNI-induced HTN and proteinuria.
** Beta-Blockers
mechanism is via mitigation of the sympathetic nervous system in failed native kidneys and decrease proinflammatory cytokines, and atherosclerosis
The side effects, including proteinuria, hyperkalemia, and masking of hypoglycemic symptoms.
** Calcium Channel Blockers
their vasodilatory effect can counteract the vasoconstrictive effect of CNIs and improve BP control
It also prevent post-transplant ATN or DGF
It can result in peripheral edema and muscle weakness
It leads to increase in both calcium channel blocker and CNI exposure levels.
** Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor Blockers (ARB)
Although ACEIs and ARBs provide antiproteinuric effect, they are not the drugs of choice during the immediate and early post-transplant HTN
** Alpha1-Antagonists
clonidine is often restarted and be tapered off during early post-transplant period. But it is rarely used as a single antihypertensive agent
certain interventions such as
transplant renal artery angioplasty ± stenting
treatment for OSA
Renal sympathetic denervation of the native kidneys
bilateral native nephrectomy
catheter ablation
In our centre
We use duretics for patients with hypervolemia
In case of patient with HTN first 3 months of transplantation we use CCBs and BBs
After 3 months of transplantation we use ACEi and ARBs especially if the patient has protienuria or polycythemia
HBPM may used to in addtion to office BP readings for the diagnosis high BP in the kidney transplant population.
Briefly summarise this article
Hypertension is common in patients with obesity, dyslipidemia and diabetes. It is an important cause of morbidity after kidney transplant. The pathogenesis is complex and may be related to immunological and non immunological factors. This articles discusses the pathogenesis, timing of intervention and types of management options.
Post transplant hypertension can be divided into:
Immediate post transplant period
Causes can be-
Peri operative hypervolemia
High dose steroids
Rebound hypertension
Inappropriate pain management
Early post transplant period
Causes can be –
weight gain
CNI
TRAS- transplant renal artery stenosis.
Hypertensive donor kidneys
Late post transplant period
Causes can be –
Chronic allograft dysfunction
FGF- Fibroblastic growth factor
Obstructive sleep apnoea
Management
The target blood pressure should be at 130/80 mm Hg
Treatment is both pharmacological and non pharmacological.
Exercise, healthy diet and less stress can help.
Medical therapy-
includes diuretics , calcium channel blockers, ACEI and ARBi, alpha blockers, aldosterone antagonists, alpha2 agonists.
Surgical options can be native Nephrectomy, Angioplasty and stenting in TRAS, denervation, catheter ablative renal denervation,
In conclusion, hypertension is a common disease in ESRD and pathogenesis is complex. Clinicians should take into account transplant and immunology while making choice of antihypertensive agents. New surgical modalities to treat hypertension can be helpful too.
Introduction:
cardiovascular diseases (CVD) is the leading cause of morbidity and mortality in kidney transplant recipients . Hypertension (HTN) is a usual finding in this population and one of the most common risk factors for CVD .
EPIDEMIOLOGY:
· Overall prevalence of post-transplant HTN has ranged from 24 to 90 %
· the prevalence of post-transplant HTN has been widely reported, and it has generally increased over time. This greater incidence of post-transplant hypertension maybe related to the introduction of cyclosporine
DEFINITION :
– definition of HTN in kidney transplant recipients remains controversial .
– In addition to the defining normal BP levels, the presence or absence of HTN during the pre-kidney transplant period may further categorize kidney transplant recipients into four groups :
1-persistent HTN
2-recovered HTN
3- persistent normotension
4-post-transplant HTN.
– The European Society of Hypertension and the European Society of Cardiology guidelines defined isolated systolic HTN in the general population as SBP ≥140 and DBP <90 mmHg . This is the most common phenotype of HTN in elderly patients .
– alternatively, diastolic HTN is defined as DBP of ≥90 mmHg, with a SBP <140 mmHg, and is more common in younger, sedentary individuals with a higher body mass index (BMI) .
– new BP guidelines and re-defined HTN for the general population as systolic blood pressure (SBP) >130 or DBP >80 mmHg .
– in kidney transplant recipients, a BP ≥130/80 mmHg may be a reasonable definition for HTN in this population
– Tighter BP control with BP <125/75 if proteinuria > <125/75 in the patient with proteinuria >1 g/day
PATHOGENESIS :
1- immediate post transplant hypertension
– pre operative hypervolemia ( particularly in patients with delayed graft function (DGF) )
– induction immunosuppression (Since a steroid dose of more than 20 mg of prednisone per day is the threshold for having HTN , high-dose IV steroids can contribute to HTN during immediate post-transplant period )
– inadequate pain control ( Opioid analgesic is commonly used for pain management during immediate post-transplant period )
– rebound hypertension ( Beta-adrenergic agonists, clonidine (both oral and transdermal forms) , and beta-blockers are commonly associated with this phenomenon, particularly when abruptly stopped )
2- early post transplant hypertension
Defined as the time between 24 and 52 weeks post-transplantation
-weight gain Obesity (BMI ≥ 30 kg/m2) after kidney transplantation is significantly associated with post-transplant HTN
-CNI , two main mechanisms :
a- altered vascular tone , increased Increased renal sodium transport handling Increased renal sodium transport handling V.C & impaired V.D
b- Increased renal sodium transport handling
>>CNI induces salt-sensitive HTN via activation of the WNK- SPAK-NCC pathway similarly to a rare genetic form of HTN , called familial hyperkalemic hypertension (FHHt, also called Gordon syndrome or pseudohypoaldosteronism type 2 , manifests as hyperkalemic hypertension with a non-anion gap metabolic acidosis and hypercalciuria
>>CNI inhibits calcineurin and leads to phosphorylation and activation of WNK and SPAK kinases and NCC. Therefore, sodium and chloride reabsorption in the DCT is increased and salt-sensitive HTN occurs. Low fractional excretion of chloride supports increased NCC activity , and a decreased plasma aldosterone level is consistent with volume expansion. So , theoretically , thiazide diuretics should be effective for CNI-induced HTN .
-maintenance steroid use
– Hypertensive Donor Kidney (study in kidney transplant recipients who had undergone native nephrectomy before transplantation from normotensive donors found that all recipients were normotensive post-transplant without need for antihypertensive therapy )
– Transplant Renal Artery Stenosis (TRAS)
>>Approximately 1–5% of post-transplant HTN is secondary to TRAS , may occur at any time after kidney transplantation but is generally diagnosed between 3 and 24 months post transplantation
>>causes : immunologicakl & non immunological factors
>>clinically :uncontrolled HTN , flash pulmonary edema , increased of s.cr after ACEI & ARBS
>>diagnosis: US doppler , CT angiography , MRA
>>management : -Patients with worsening serum creatinine and/or uncontrolled HTN attributable to TRAS should undergo renal artery angioplasty with stenting
-Surgical revascularization is reserved for cases of unsuccessful angioplasty.
3- Late Post-transplant Period :
– Chronic Renal Allograft Dysfunction
– Fibroblast Growth Factor (FGF) 23
- Obstructive Sleep Apnea
>> risk factors for OSA in kidney transplant recipients are male gender, obesity, use of hypnotic drugs, presence of severe comorbidity (e.g., heart disease, cerebrovascular disease, peripheral vascular disease, diabetes mellitus), and impaired kidney function
>> appropriate management of OSA is an essential component of the antihypertensive therapy in kidney transplant recipients who later develop renal allograft dysfunction especially with resistant HTN
OUTCOMES :
Increased post-transplant SBP and DBP were associated with progressively decreased renal allograft function and death-censored chronic graft failure
BLOOD PRESSURE MEASUREMENT :
-office blood pressure (OBP)
– home blood pressure monitoring (HBPM) , recording at least twice the daily average of two home blood pressure readings over a minimum of 4 days
– 24- h ambulatory blood pressure monitoring (24-h ABPM), which requires wearing an electronic blood pressure measurement device to record and averages multiple readings over a 24 h period
MANAGEMENT :
– Non-pharmacologic : such as diet, exercise, and stress reduction for all patients.
-pharmacological :
>>Antihypertensive medication :
• Diuretics – Loop ( volume control & VD effect , s/e>>volume depletion , electrolyte disturbance )
– Thiazides ( espi in CNI induced hypertension with hyperkalemia & hypomagnesemia)
• Calcium channel blockers (>> 1st line due to VD effect , also prevent post-transplant acute tubular injury (ATI) or DGF , s/e>>peripheral edema & muscle weakness
>> Non-dihydropyridine calcium channel blockers inhibit CYP3A4 isoenzyme and significantly increase CNI level. )
• Beta-blockers (have cardioprotective effects and survival benefit , decrease proinflammatory cytokines, which are known to increase the risk for atherosclerosis , s/e >>hyperkalemia , proteinuria & masking hypoglycemia symptoms )
• Renin-Angiotensin Aldosterone System blockade – Angiotensin-converting enzyme inhibitors – ARB, angiotensin II receptor blockers – Mineralocorticoid receptor antagonists
>>avoid in early period post transpalnt
• Alpha1 antagonists( djunctive therapy)
• Alpha2 agonists (>>Centrally acting , work on presynaptic alpha2 adrenoceptors in the central nervous system and suppress central sympathetic activity
· clonidine>> associated with weight gain and progressive resistance with continued use.
>> rebound HTN is common after discontinuation of clonidine, and patients who are on clonidine prior to kidney transplant tend to have uncontrolled HTN resulting from this rebound phenomenon. In these patients, clonidine is often re-started and be tapered off during early post-transplant period
· methyl dopa>> associated with antihypertensive tolerance, edema, and weight gain
· Procedural or surgical interventions Specific treatment modalities :
– Transplant renal artery angioplasty ± stenting
– Continuous positive airway pressure (CPAP)
– Bilateral native nephrectomy
– Native renal denervation
CONCLUSIONS :
– HTN is a very common disease in CKD and ESRD and remains so after kidney transplantation. The pathogenesis of post-transplant HTN is complex. BP measurement is still the main barrier to accurately diagnose and follow-up in HTN management. A 24-h ABPM, though the gold standard, is inconvenient and not wildly utilized.
-The choice of antihypertensive medication requires the clinician to take transplant and immunological factors into the consideration. Management for OSA and interventions for resistant HTN, such as transplant renal artery angioplasty ± stenting, bilateral native nephrectomy, and native RDN, remain options for resistant HTN in selected kidney transplant recipients.