V. Outcomes of Hypertensive Kidney Donors Using Current and Past Hypertension Dentitions
-
- Please summarise this article in your own words
- What is the level of evidence provided by this article?
- Please reflect on the guidelines and refer to your practice.
Thank you All for your responses
Will you change your practice based on this article, and why?
Please reflect on the guidelines also.
What are the limitations of this study?
Thanks you very much ourProf.Halawa
Thank you
The current study has the following limitations:
So … my answer is No … I will not change my practice based on this article and I will follow the British guidelines in accepting or deferring a donor regarding BP
Evaluation of BP before kidney donation
Guidelines for safe donation (regarding BP)
Thank you
● Third of kidney donors developed hypertension 15 years after donation compared with <10% in non-donor healthy control
● Definition of hypertension :
◇ Pastly : BP >=140/90 mm Hg or the requirement for antihypertensive agents
◇ Newly introduced hypertension definition (>=130/80 mm Hg)
● Postdonation hypertension was defined as use of antihypertensive medications specifically used for hypertension treatment or a documented home, center, or office-based BP >=140/90 mm Hg.
● 8922 kidney donors, 8721 donated a kidney between 1963 and 2007 had multiple predonation BP measurements available
● 904 hypertensive donors (blood pressure BP >140/90 mm Hg or receiving treatment) versus 7817 donors with BP <140/90 mm Hg.
● Follow up 14.3 years
● Outcomes :
Mortality, CVD, proteinuria, eGFR , reduced eGFR, ESKD
● Results:
** Hypertensive donors were older
** 58.1% were <50 years of age
** they had a lower eGFR.
** The majority were white and related to their recipient.
** Hypertensive and non-hypertensive donors had a similar prevalence of cardiovascular disease and renal outcomes.
** The multivariable risk of mortality, CVD, and proteinuria were also comparable in normotensive and hypertensive donors.
** eGFR slope over time was similar in hypertensive and nonhypertensive donors
** 5 hypertensive and 39 normotensive donors developed ESKD 19.2 years after donation
** Sensitivity analysis using the new definition of hypertension (>130/80 mm Hg or requiring treatment)
** Similar results for renal outcomes
hypertensive donors were more likely to develop CVD and diabetes.
● Conclusions: Kidney donors with hypertension defined by past criteria do not appear to incur higher mortality, CVD, or ESKD. Donors with current definition of hypertension enjoyed similar renal outcomes but were more likely to develop CVD.
● Limitations:
** No aviliable data for causes of ESKD in donors
** No standered BP measurements
** Higher proportion of particular ethinicity can lead to tipping results
** Normotensive donors have not been captured in data thus may actually mask actual hypertention data
● level evidence III
● In our practice we exclude hypertension donors even they controlled and have no endorgan damage
Upon this article I will reconsider these donors for donation
● Reflect on guidlines
◇ Blood pressure must be assessed on at least two separate occasions. Ambulatory blood pressure monitoring or home monitoring is recommended if blood pressure is high, high normal or variable, or the potential donor is on treatment for hypertension.
◇ We suggest that a blood pressure <140/90 mmHg is usually acceptable for donation
◇ Potential donors with mild-moderate hypertension that is controlled to <140/90 mmHg (and/or 135/85 mmHg with ABPM or home monitoring) with one or two antihypertensive drugs and who have no evidence of end organ damage may be acceptable for donation. Acceptance will be based on an overall assessment of cardiovascular risk and local policy.
Thank you
The limitations of this study were:
Thank you, agree
Thank you.
limitation of this study he population of non -Hispanic white donors in the RELIVE study was significant higher than in the US donor pool(70%).
Proportion of Hispanic and Asian donors were less than what is observed.
The RELIVE study does not have cause of ESRD in donor,
There was no standardized of how BP measure at 3 occasion.
Non Hispanic white HTN donors do not have an increased risk of ESRD compared with normotensive kidney donors.
iwill not change my practise unless there is strong evidence or guidelines regarding HTN kidney donors.
Thank you, Manal, but there is a shred of clear evidence to support donation from hypertensive donors who are on 2 medications, provided that the blood pressure is well controlled and no end organ damage
The limitations of this study were:
Large proportion were non-Hispanic whites – African Americans are at a higher risk of developing HTN and proteinuria
Cause of ESKD in donors is not known
No standardization of how BP measurements were carried out in the three centers
So … my answer is No … I will not change my practice based on this article and I will follow the British guidelines in accepting or deferring a donor regarding BP
Guidelines for safe donation (regarding BP)
Donors with clinic BP ≺ 140/90 mm Hg (≺135/85 mmHg if using ABPM or home monitoring) on no antihypertensive medications can proceed safely to kidney donation
Donors with clinic BP ≺ 140/90 mm Hg (≺135/85 mmHg if using ABPM or home monitoring) on 1 or 2 antihypertensive medications can proceed safely to kidney donation provided there is no evidence of end organ damage (LVH, albuminuria, retinopathy)
Donors with clinic BP ≥ 140/90 mm Hg on 2 antihypertensive medications an should be excluded from donation
Donors receiving more than 2 antihypertensive medications or having end organ damage should be excluded from donation
Thank you, Maksouda. This is much better.
Yes for sure this article will change our practice in considering evaluation od donors diagnosed as hypertensive, inorder to maximize donor pool, donors with high BP on 2 AHM controlled with no EOD, can proceed for donation
Also other than hypertension as a risk factor, considering other factor that can agrevate the condition e.g; DM, dyslipidemia, BMI>30, obesity, smoking and CVD.
Limitation:
Its a prospective study utilized the data from Relive study for kidney donors between 1964 and 2007 involving 8721 donors with 904 hypertensive donors to ascertain the outcome of donation for hypertensive donors with special emphasis on the cardiovascular and renal morbidity and mortality .
They censored the outcome according to the previous cut off hypertension of 140/90 and compare it with the latest SPRINT study based new guideline with cut off of 130/80. The donors were hypertensive as per the old criteria of 140/90 therefore this study was conducted to verify those hypertensive donor in addition to the de novo hypertensives outcome after 14 {plus, minus 10 } years of follow up. characteristically, hypertensive donors were older, Caucasians and with less eGFR.
In brief, This study concluded the equivalent incidence of cardiovascular and renal outcome of both hypertensive and non hypertensive donors. nevertheless, when the new guideline hypertension limits applied ,1465 would be diagnosed with hypertension and the complications are variable with higher incidence of cardiovascular adverse outcome , Diabetes mellitus and higher mortality rate in hypertensive donors versus non hypertensive donors. Similarly, the incidence of developing hypertension is increasing to 1/3 of donors as per the current new guideline.
Caveats of the study:
1}The patients come from 3 transplant centers versed in life donors transplantation.
2}The non-Hispanic donors proportion is higher than the other ethnicity.
3}The cause of ESKD in donors was not identified.
4}It would be prudent to know the consequences of transplanting kidney from hypertensive donor.
5}No Standardization of blood pressure measurement in the 3 centers.
6} The diagnosed hypertension might be simply white coat hypertension .. On the other hand Masked hypertension might be missed .
In my opinion , I would continue the practice and evaluate the hypertensive patients according to the recent guideline in the context of other underlying cardiovascular risk factors.
Will you change your practice based on this article, and why?
Yes, will accept those donors with HTN controlled in two anti hypertensive patients, that we usually decline them, in order to increase donor pool.
Limitations of the study:
= The study conducted from 3 transplant centers donors, which differ in ethnic group than the population in RELIVE.
= No standardized method to monitor B/P among the three centers, the lowest reading of three B/P reading considered baseline B/P, not identifying the masked HTN.
= Poor performance of eGFR estimating models in those with GFR >60 ml/min and the fact that the serum creatinine assay has certainly changed over the almost 5 decades of the RELIVE study.
Having a large number of white relative to black, Hispanic or non-Hispanic etc may not that important in terms of limitation, but the evaluation or confirmation of hypertension itself may be a limitation.
Young patients with multiple drugs, even if controlled HT with no end organ problems, may have a greater risk in future, especially with the loss of nephron mass.
In accordance with BTS guidelines, it is recommended to exclude donors not controlled with one or 2 drugs (the aim is less than 140/90). BTS guidelines grade acceptance of blood pressure <190/10 is acceptable but with a grade (C1).
**My opinion and what we do is accept patients who have controlled BP <130/80 on max. 2 drugs with stable renal function and no evidence of CVD or kidney injury (stable renal function over time and no proteinuria.
In our transplant unit, we consider hypertensive donors if they have well controlled blood pressure on maximum 2 antihypertensives and there is absence of any target organ damage.
Post-donation, they are advised to maintain a healthy lifestyle, keep BP under control and to remain under regular follow-up.
The results of this study give confidence to both the donor as well as the transplant team that if chosen after requisite diligence, a hypertensive donor with well controlled BP on maximum 2 antihypertensives and without target organ damage, the results are similar to those without hypertension.
Hence this study acts as a confidence booster for our unit that the practice being followed is evidence based.
The limitations of the study include disproportional distribution of ethnicity in the study population with respect to the general population, lack of data regarding etiology of ESRD in the recipients, lack of data regarding outcome of hypertensive donor’s kidney in the recipient, and lack of data regarding method of measurement of BP in the 3 centres (whether it was standardized or not).
Based on the article, and with references to the guidelines, I believe that the limitation is to do with race limitation that is there wasn’t a large or broad distribution. Also, there was no reason given for graft failure. There was no record of lifestyle modifications to help control blood pressure. Blood pressure measurement was not identified.
Patients with BP greater than 140/90 mmHg on 2 or more medications should not be included as part of the donor.
BP 140/90mmHg with one medication can be considered.
BP less than 140/90 on no medication or on medications can be considered to be part of the donation pool.
Proper follow-up must be done.
No I will not change my practice based on this study because the study has lot of limitations:
As per BTS guidelines if hypertension is controlled (< 140/90) on one or two antihypertensive drugs without any end organ damage, then donor can be considered for donation
Yes we will considered hypertensive donors with good control by two medication .
Limitation:
Public dataset does not have the cause of ESKD in donors.
No standardization of how BP measurements were carried out at the three centers.
Non-Hispanic white donors in the RELIVE study was significantly higher
Hypertension being the most common and major risk factor for CVD, CVAs and PVD.Previously it was defined as B.P>140/90.These days B.P >130/80 or more is considered as hypertension.
This RELIVE study recruited 8922 donors from 1963-2007 and average B.P noted after taking three readings and donors approached via mail and followed up for 4–48 years and inquired about QoL, development of DM, Hypertension,CVD, kidney disease & other conditions.
Results:
Elderly, male, white and those with lower GFR and high BMI have Hypertension. ESRD was low (0.6%) in hypertensive donors. Cardiovascular diseases and renal outcomes similar between hypertensive and non-hypertensive donors. However ,cardiovascular outcomes more common in hypertensive patients (new criteria) compared to the old definition of hypertension.Major limitations of the study are ESRD cause not mentioned in the study and no standard B.P measurement incuded.
Donors with B.P (≺135/85 mmHg if using ABPM or home monitoring) or on no antihypertensive medications, or donors with B.P (≺135/85 mmHg if using ABPM or home monitoring) on single or two antihypertensive medications without target organ damage can be considered for donation however, if the patient has B.P >140/90 on two or more antihypertensives with target organ damage then should not be considered for donation.
Retrospective cohort study-level of evidence III
At our center, we also follow similar guidelines and also counsel the donor to adopt lifestyle measures i.e., smoking cessation, reducing alcohol intake, exercise regularly after donation to reduce CVD ,hypertension and proteinuria after donation.
Ø Study the mortality, CVD, proteinuria, estimated glomerular filtration rate (eGFR) trajectory, reduced eGFR, and end-stage kidney disease (ESKD) in 904 hypertensive donors (blood pressure [BP] 140/90 mm Hg or receiving treatment) versus 7817 donors with BP <140/90 mm Hg.
Ø Hypertensive donors were older, 58.1% were <50 years of age, and they had a lower eGFR. The majority were white and related to their recipient.
Ø At the end of follow-up, 14.3+/- 10.1 years (range 4–48 years) from donation, hypertensive and nonhypertensive donors had a similar prevalence of cardiovascular disease and renal outcomes.
Ø The multivariable risk of mortality, CVD, and proteinuria were also comparable in normotensive and hypertensive donors. eGFR slope over time was similar in hypertensive and non-hypertensive donors, and in total 5 hypertensive and 39 normotensive donors developed ESKD 19.2 +/-10.3 years after donation (adjusted hazard ratio 1.14 [95% confidence interval 0.62–2.12], P ¼ 0.67).
Ø Sensitivity analysis using the new definition of hypertension (130/80 mm Hg or requiring treatment) yielded similar results for renal outcomes, but hypertensive donors were more likely to develop CVD and diabetes.
Ø In summary kidney donors with hypertension defined by past criteria do not appear to incur higher mortality, CVD, or ESKD. Donors with current definition of hypertension enjoyed similar renal outcomes but were more likely to develop CVD
Level 3
This is a retrospective cohort study with level 3 evidence to study the outcome of hypertensive kidney donors.Hypertensive donors were older, 58.1% were <50 years of age, and they had a lower eGFR. The majority were white and related to their recipient. At the end of follow-up, 14.3 ± 10.1 years (range 4–48 years) from donation, hypertensive and nonhypertensive donors had a similar prevalence of cardiovascular disease and renal outcomes. The multivariable risk of mortality, CVD, and proteinuria were also comparable in normotensive and hypertensive donors. eGFR slope over time was similar in hypertensive and nonhypertensive donors, and in total 5 hypertensive and 39 normotensive donors developed ESKD 19.2 ± 10.3 years after donation (adjusted hazard ratio 1.14 [95% confidence interval 0.62–2.12], P = 0.67). Sensitivity analysis using the new definition of hypertension (≥130/80 mm Hg or requiring treatment) yielded similar results for renal outcomes, but hypertensive donors were more likely to develop CVD and diabetes.
The strengths include the studied population spans 50 years of kidney donation, is ethnically diverse. There are limitations such as no standardization of how BP measurements were carried out at the 3 centers, and many donors labeled as hypertensive may have simply had white coat hypertension.
In conclusion, kidney donors with hypertension defined by past criteria do not appear to incur higher mortality, CVD, or ESKD. Donors with current definition of hypertension enjoyed similar renal outcomes but were more likely to develop CVD.
In my opinion, I wont accept kidney donor with poor BP control.
Introduction: Many transplant centers in the United States will not accept kidney donor candidates who have hypertension, referencing the link between hypertension, kidney disease, and cardiovascular disease (CVD). Furthermore, a recent study found that roughly one-third of kidney donors developed hypertension 15 years after donation, compared to 10% of non-donor healthy control subjects. In a separate study conducted by the same researchers, pre-donation hypertension in donors over the age of 50 was associated with an overall ESKD incidence of 1%. Strict blood pressure control in the SPRINT study, while significantly associated with lower mortality, did not appear to reduce CKD incidence, at least according to its traditional definition of eGFR 60 ml/min/1.73 m2.
Because the definition of hypertension has evolved over time, many kidney donors who donated in the past, particularly early in the history of transplantation, would be considered hypertensive by today’s standards. Because donors have no evidence of any renal involvement, such as proteinuria or low GFR, and no major comorbidities at donation, this provides a unique opportunity to study the impact of isolated hypertension on long-term kidney function, and thus the temporal relationship between hypertension and kidney disease can be better analyzed.
Methods: ascertained mortality, CVD, proteinuria, estimated glomerular filtration rate (eGFR) trajectory, reduced eGFR, and end-stage kidney disease (ESKD) in 904 hypertensive donors (blood pressure [BP] >140/90 mm Hg or receiving treatment) versus 7817 donors with BP <140/90
Results:
· Hypertensive donors were older, 58.1% were <50 years of age, and they had a lower eGFR.
· The majority were white and related to their recipient.
· At the end of follow-up, 14.3 ± 10.1 years (range 4–48 years) from donation, hypertensive and non-hypertensive donors had a similar prevalence of cardiovascular disease and renal outcomes.
· The multivariable risk of mortality, CVD, and proteinuria were also comparable in normotensive and hypertensive donors.
· eGFR slope over time was similar in hypertensive and non-hypertensive donors, and in total 5 hypertensive and 39 normotensive donors developed ESKD 19.2 ± 10.3 years after donation (adjusted hazard ratio 1.14 [95% confidence interval 0.62–2.12], P ¼ 0.67).
· Sensitivity analysis using the new definition of hypertension (≥130/80 mm Hg or requiring treatment) yielded similar results for renal outcomes, but hypertensive donors were more likely to develop CVD and diabetes.
Conclusions: Kidney donors with hypertension as defined by previous criteria do not appear to have a higher risk of death, CVD, or ESKD. Donors with current hypertension definitions had similar renal outcomes but were more likely to develop CVD.
What is the level of evidence provided by this article?
Level 3
Please reflect on the guidelines and refer to your practice.
We don’t accept the donors with hypertension in our centre
The Renal and Lung Living Donor Evaluation (RELIVE) study that involved 8922 living renal donors between 1963 and 2007 was the base of this project.6352 (72.8%) were involved among 8922 living renal donors had SBP <130 mm Hg, 1465 (16.8%) had 130< SBP < 140 mm Hg, 653 (7.5%) had SBP >140 mm Hg, and 251 (2.9%) were using antihypertensive agents.
Hypertensive donors (904) were older (48 vs. 38) years mostly nonrelated men. They had significant increased weight, BMI, SBP, DBP, and a lower eGFR (83 vs. 89) ml/min/1.73 m2.
251 hypertensive donors received antihypertensive agents, 154 received monotherapy, 44 received dual therapy, 5 used triple therapy while in 43 donors this information was missing.
Hypertensive donors on treatment were average 7 years older than untreated ones, mostly nonrelated white, besides displaying lower SBP and DBP at donation (133 vs. 145 mm Hg for SBP and 80 vs. 84 mm Hg for DBP).
Hypertensive donors on antihypertensive therapy also had a 10 ml/min/1.73 m2 lower baseline eGFR than hypertensive donors not receiving any treatment (P <0.001).
SBP was increasing by 2.2 mm Hg per decade (95% confidence interval [CI] 1.8–2.6) in non-hypertensive donors versus -0.3 mm Hg per decade (95% CI -1.6 to 1.1) in hypertensive donors.
The difference in slope was significantly different (P <0.001). DBP was higher by 1.1 mm Hg per decade (95% CI 0.8–1.3) in non-hypertensive donors versus -1.1 mm Hg per decade (95% CI -2.0 to 0.3) in hypertensive donors (P < 0.001).
2319 donors developed hypertension 5.1+ 9.2 years post donation. These donors were younger at donation time (40 vs. 48 years of age). They were non- related to the recipient of higher baseline eGFR and lower BMI, as well as family history of HTN was free.
Post donation hypertension development was linked to older age [aHR] 1.02 [95% CI 1.02–1.03]), male (aHR 1.31 [95% CI 1.19–1.44]), BMI (aHR 1.06 [95% CI 1.05–1.08]), and fasting plasma glucose (aHR 1.01 [95% CI 1.006–1.01]; P < 0.05 for all).
17.6 to 10.7 years post donation to last follow-up in 2010 to 2012 in donors without hypertension, and about 14.3 to 10.1 years for donors with hypertension; it was found that:
The proportion was similar regarding no mortality (4.7% vs. 6.0%, P = 0.09)
The incidence of CVD (12.7% vs. 13.9%, P= 0.31).
Prevalence of DM (7.1% vs. 8.2%, P= 0.26).
The incidence of development of proteinuria was more in Hypertensive donors (17.8% vs. 13.4%, P < 0.001), these donors also had decline in eGFR < 60 and < 45 ml/min/1.73 m2.
Development of ESRD or decline of eGFR < 30 ml/min/1.73 m2 was estimated to be the same in both populations (6.6 [95% CI 4.8–9] vs. 10.9 [95% CI 4.5–75.2]) per 10,000 donor-years (P= 0.3).
Hypertensive donors who developed ESRD were characterized by high BMI at donation and family history of HTN.
There was no ESRD incidence at all in HTN donors by 10 years post donation.
Prevalence of ESRD by 30 years post donation was 51.8 (95% CI 27–99.6) per 10,000 donor-years in normotensive donors vs 61.5 (95% CI 8.7–436.6) in hypertensive donors (P=0.30).
Reduction of eGFR < 30 ml/min/1.73 m2 or ESRD was detected in 86 donors; 72 (0.9%) in normotensive donors and 14 (1.6%) in hypertensive donors.
Hypertensive donors showed evidence of higher serum creatinine level over time.
Hypertensive donors were less prone to die or develop cardiovascular disease, or
proteinuria or decline of eGFR, or even ESRD.(aHR for occurrence of ESRD was 1.14 (95% CI 0.62–2.12, P=0.67).
The incidence of development of CVD associated with hypertension (aHR 1.34 [95% CI 1.05–1.51], P=0.02). It showed no comparable significance between both groups as the incidence of CVD in normotensive donors aHR 1.27 (95% CI 0.96–1.68, P=0.09).
Hypertensive donors compared to non-hypertensive donors in terms of decline of eGFR, proteinuria, ESRD, CVD or even death are not of increased risk except for those matching new definition of HTN ; they may develop CVD or DM.
The risk of ESRD in African American 3% may be not due to HTN, as hypertension itself may be related to CKD development owing to APOL1 polymorphism.
This study found that SBP increased by 2.2 mm Hg per decade in normotensive donors at time of donation, which is evidently comparable to our previously described rate of 2.9 mm Hg per decade in a longitudinal study of 4296 renal donors between 1963 and 2014.
This study showed hypertensive donors able to donate if BP is well controlled, no proteinuria and no end organ damage (no left ventricular hypertrophy or hypertensive retinopathy).
Strengths
large span of 50 year duration, different ethnicities
Addressing unusual different items in this study as GFR decline, serial serum creatinine, proteinuria assessment, CVD and DM.
Limitations
white coat hypertension, or normotensive donors having masked hypertension.
ESRD display low statistical as it is generally a less likely event rate to occur. Other unexplained issue is the surprisingly high eGFR in all donors.
Level of evidence III.
Introduction
Hypertension is well recognised leading cause of ESKD .
It was suggested that around one third of kidney donors developed hypertension 15 years after donation.
In many cases, hypertension follows the development of CKD rather than precedes it.
While definition of hypertension has changed
many kidney donors in the past would be considered hypertensive today.
follow-up of these donors allows good understanding of relationship between hypertension and kidney disease.
So this study was done to determine long term outcomes after donation in hypertensive and normotensive donors.
Method
This study from 3 US centers data collected from the national database from The Renal and Lung Living Donor Evaluation (RELIVE) study from 1963-2007, includes> 8922 donors and 8721 donated a kidney between1963 and 2007, had multiple pre-donation BP measure and vitals available in 99.8% .all data recorded from each center including donors’ demographics, clinical characteristics, family history of HTN, DM CKD, Bp measurement in 3 occasions and as per the extant definition at the time of the study, which was BP >140/90 mm Hg or the requirement for antihypertensive agents, between 2010-2012 the data sources were based on personal records through communication by phone, emails, and an internet connection, including quality of life surveys in addition to the recipient’s information about their donors. So most of the FU records about DM, HTN, CVD it’s by self-reporting by the donors, proteinuria defined as urine dipstick protein >2þ, urine protein/osmolality ratio >0.42, urine random protein >15 mg/ dl, or 24-hour protein >300 mg/day.ESKD is defined as the need of dialysis or listed for kidney transplant waiting .
The new definition of hypertension (>130/80 mm Hg or requiring treatment)
Results
Hypertensive donors were older, more likely to be men, less likely to be related to the recipient, and more likely to have a college education.
Hypertensive donors had a higher weight, BMI, SBP, DBP, and a lower eGFR(83vs89), 251 of them were receiving one or more anti hypertensive medication and were in average 7 years elder than untreated ones.
Donors with postdonation hypertension were younger at donation, less likely to be related to the recipient, had a higher baseline eGFR, a lower BMI, and were less likely to have a first-degree relative with hypertension.
post-donation HTN more in older patients , males, higher BMI, and fasting plasma glucose level.
= Hypertensive donors were more likely to have proteinuria (P < 0.001) and more likely to have an eGFR < 60 and < 45 ml/min/1.73 m2 , but no increased risk of ESKD (increased in donors with first degree relative with HTN, and high BMI).
= Hypertensive donors had a significantly higher serum creatinine level over time, but eGFR trajectory was comparable in donors with and without hypertension.
= Donors who fulfilled the more recent definition of hypertension had comparable renal outcomes to nonhypertensive donors but were more likely to die (P= 0.051), were more likely to develop CVD (P < 0.001), and were more likely to develop diabetes (P = 0.01).
= Hypertensive donors, compared with nonhypertensive donors, are not at increased risk for reduced eGFR, proteinuria, or ESKD, but according to recent criteria for HTN they were more to have CVD and to develop diabetes.
Conclusion :
Kidney donors with hypertension defined by past criteria do not appear to incur higher mortality, CVD, or ESKD.
Donors with current definition of hypertension enjoyed similar renal outcomes but were more likely to develop CVD, and DM.
Donor candidates with hypertension, particularly white donors, can be considered for donation provided that subtle renal disease is ruled out.
What is the level of evidence provided by this article?
Level of evidence III
The data of the Renal and Lung Living Donor Evaluation (RELIVE) study that evaluated outcomes of 8922 kidney donors from 3 U.S. transplant centers: the University of Minnesota, Mayo Clinic-Rochester, and the University of Alabama-Birmingham are used. All donations took place between 1963 and 2007. 201 were excluded. Donors’ medical records were abstracted at each of the participating centers. BP readings were collected on multiple occasions during the donor evaluation, and the average of the 3 lowest readings was used as baseline to minimize misclassifying donors with white coat hypertension as truly hypertensive as described by Taler et al. Hypertension was defined by the extant definition at the time of the study, which was BP >140/90 mm Hg or the requirement for antihypertensive agents.
Of 8922 kidney donors, 8721 donated a kidney between 1963 and 2007, had multiple predonation BP measurements available, and had their vital statuses ascertained . Vital status was ascertainable in 99.8% of the donors, CVD in 98%, eGFR value in 97.1%, postdonation hypertension in 98%, postdonation diabetes in 90.2%, and proteinuria data in 89.9%.
Hypertensive donors (n ¼ 904) were older (48 vs. 38 years), more likely to be men, less likely to be related to the recipient, and more likely to have a college education . Hypertensive donors had a higher weight, BMI, SBP, DBP, and a lower eGFR (83 vs. 89 ml/min/1.73 m2). Of the 251 hypertensive donors receiving antihypertensive medications, 154 received 1 agent, 44 received 2, 5 used 3 agents, and in 43 donors this information was missing. Hypertensive donors receiving treatment were on average 7 years older than untreated hypertensives, were more likely to be white, were less likely to be related to their recipient, and had a significantly lower SBP and DBP at donation (133 vs. 145 mm Hg for SBP
At the end of follow-up, 14.3 + 10.1 years (range 4–48 years) from donation, hypertensive and nonhypertensive donors had a similar prevalence of cardiovascular disease andrenal outcomes.The multivariable risk of mortality, CVD, and proteinuria were also comparable in normotensive and hypertensive donors. eGFR slope over time was similar in hypertensive and nonhypertensive donors, and in total 5 hypertensive and 39 normotensive donors developed ESKD 19.2+10.3 years after donation . Sensitivity analysis using the new definition of hypertension ( >130/80 mm Hg or requiring treatment) yielded similar results for renal outcomes, but hypertensive donors were more likely to develop CVD and diabetes.
These analyses have strengths. The population studied spans 50 years of kidney donation, is ethnically diverse, and donors had ascertainable intermediate renal outcomes, such as reduced GFR, serial serum creatinine availability, proteinuria assessment, and CVD, which are not captured in national donor databases. There are limitations, however. Donors included in this analysis come from 3 major U.S. transplant centers with a longstanding tradition in live kidney donation and while ethnically diverse, the proportion of non-Hispanic white donors in the RELIVE study was significantly higher than what is observed in the larger U.S. donor pool, which is approximately 70%. Moreover, the proportions of Hispanic and Asian donors were less than what is observed nationally. The RELIVE study public dataset does not have the cause of ESKD in donors and it would also have been ideal to know how kidneys from hypertensive donors fared in the recipients. Importantly, there probably was no standardization of how BP measurements were carried out at the 3 centers, and many donors labeled as hypertensive may have simply had white coat hypertension.
level of evidence II
Outcomes of Hypertensive Kidney Donors Using Current and Past Hypertension Definitions
Hypertension is stablished as a cause of ESRD. Reduction in renal mass is associated with development of hypertension. Third of kidney donors developed hypertension 15 years after donation compared with < 10% in nondonor healthy control subjects. Hypertension accelerates progression of kidney disease.
The definition of hypertension has evolved over years, and therefore many kidney donors who donated in the past, particularly at the start of transplantation history, would be considered hypertensive by today’s standards. This provide unique opportunity to study the impact of hypertension in these donors who was fit with no any comorbidities at the time of donation. Therefore, the temporal relationship between hypertension and kidney disease can be better dissected. Also, this knowledge impact donor criteria selection, and determining outcomes of donors using the newly introduced hypertension definition (≥130/80 mm Hg). Collectively these will affect donor pool.
Method:
Data from RELIVE study, and NIAID-study that evaluated outcomes of 8922 kidney donors from 3 U.S. transplant centers. All donations took place between 1963 and 2007.
Hypertension was defined as BP ≥ 140/90 mm Hg or the requirement for antihypertensive agents.
Donors were asked to provide responses to quality of life surveys and were asked about developing diabetes, hypertension, kidney disease, CVD, cancer, and other conditions.
Post-donation hypertension defined as BP ≥ 140/90 or use of antihypertensive drugs
CVD was defined as diagnosis of MI, CHF, stroke, or the need for coronary or peripheral arterial interventions.
Proteinuria was defined as any of the following: urine dipstick protein ≥ 2+, urine protein/ osmolality ratio >0.42, urine random protein >15 mg/dl, or 24-hour protein >300 mg/day.
CKD-EPI equation used to estimate e GFR. ESRD was defined by the need for dialysis or being listed or receiving a transplant.
Data was studied using the old definition of hypertension and new definition as well.
Results:
All targeted variables were determined in about 90% of the studied group.
The mean age was 39 years, 56.2% were women, 85% were non-Hispanic white, 9.2% were non-Hispanic black, 1.8% were Hispanic. 0.95 were Asian.
Majority donate to family member. Median BMI was 25.8 kg/m2. Median e GFR was 88 ml/min/1.73m2.
72.8% had SBP > 130 mmHg, 16.8% had BP between 130 and 140 mmHg, and 7.5% had SBP ≥ 140 mmHg, and 2.9% were receiving antihypertensive medication.
General characteristics of donors with hypertension:
They are older (48 vs. 38 yrs), more likely to be men, unrelated to the recipient, and likely to have college education.
Hypertensive donors had higher weight, BMI, SBP, DBP, and a lower e GFR.
Hypertensive donors receiving treatment were on average 7 years older than untreated hypertensive donors, and more likely to be white. Had lower SBP and DBP at donation and less likely to be related to their recipients. Also, these donors had a 10 ml/min/1.73 m2 lower baseline e GFR than hypertensive donors not receiving treatment. The study also compares observed and predicted SBP and DBP in both groups.
Post-donation hypertension:
The development of post-donation hypertension was associated with old age, male gender, high BMI, and high FBS.
Outcomes of Interest at Last Follow-Up
Hypertensive donors are likely to have proteinuria, lower e GFR < 60 ml/min/1.73m2. however, the occurrence of e GFR < 30 or ESRD were similar in hypertensive and non-hypertensive donors.
The development of ESKD in hypertensive donors was associated with BMI at donation and having a first-degree relative with hypertension. The overall ESKD
incidence rate was similar in hypertensive and non-hypertensive donors. No ESRD cases occurred in hypertensive donors in the first 10 years. After 30 years the incidence was 51.8 per 10,000 donor-years in normotensive and 61.5 in hypertensive donors.
e GFR < 30 occurred in 0.9% in normotensive and 1.6% in hypertensive donors.
Multivariable Risks of Mortality, CVD, and ESKD
we found that hypertensive donors were not more likely to die, develop cardiovascular disease, develop proteinuria, have a reduced eGFR, or have ESKD
only, the CVD outcome was significantly associated with hypertension.
Donors who fulfilled the more recent definition of hypertension had comparable renal outcomes to nonhypertensive donors but were more likely to die
Conclusion:
Hypertensive donors, compared with nonhypertensive donors, are not at increased risk for reduced eGFR, proteinuria, or ESRD. Also, more likely to die or develop CVD. Donor fulfilling the new definition of hypertension are more likely to develop CVD and diabetes.
In all, the study shows that predominantly nonHispanic white hypertensive donors do not have an increased risk of ESRD compared with normotensive kidney donors. As well; e GFR change after donation and proteinuria development were also similar between hypertensive and normotensive donors. According to these data; donor candidates with hypertension, particularly white donors, can be considered for donation provided that subtle renal disease is excluded and a hypertensive donor is not at an increased risk for future CVD on a background of other risk factors.
Level III
in our practice, the hypertensive donor does not considered for donation even on a single drug.
Definition of hypertension has always been debatable. Frequent changing the cut off points for labelling hypertension affects various treatment protocols.
Also ,the outcomes of hypertensive living kidney donors also gets modified through changing definitions of hypertensions.
This study tries to evaluate hypertensive kidney donors with respect to mortality, CVD, proteinuria, eGFR and ESRD.
The follow up period in the study extended from 4 to 48 years.
This study determine outcomes of donors using the newly introduced hypertension definition of > 130/80 mm Hg.
Data were extracted from RELIEVE study without fresh recruitment.
Data were analyzed using Pearson’s and Fischer exact test.
RESULTS
-Hypertensive donors were older, more likely to be white men, less likely related to the recipient
Hypertensive donors had higher BMI, SBP, DBP, and a lower eGFR
-The development of hypertension following donation was associated with older age, male gender and increased BMI
-Hypertensive donors were not having high mortality , not more developing cardiovascular disease, not frequently developing proteinuria, have reduced eGFR, or have ESKD
Study level of evidence is 3
Donors with blood pressure controlled with 2 medications could be accepted for donation
Please summarize this article in your own words
This is a retrospective study.
Aim: compare kidney donors with BP>140/90 vs donors with BP <140/90 regarding mortality, GFR, proteinuria, ESRD development and CVD.
Study population:
1- 904 kidney donors with BP 140/90 or above.
2- 7817 kidney donors with BP below 140/90.
Follow up: 14.3 +/- 10.1 years.
Results:
1- Donors with high BP were older, men, white origin, high BMI, lower GFR and related to recipients.
2- Risk of ESRD was low in both groups, 0.6% in HTN group and 0.5 % in non-HTN group.
3- No difference between both groups regarding mortality, GFR, Proteinuria, and ESRD development using old and new definitions of Hypertension.
4- CVD was more common in HTN group when using BP 130/80 or more or the need for anti-HTN agent.
Blood pressure guidelines for safe donation:
1- Donors with BP below 140/90 or below 135/85 using ABPM without anti-hypertensive medications can proceed for donation.
2- Donors with BP below 140/90 or below 135/85 ABPM on 1 or 2 anti-hypertensive agents without evidence of end organ damage can proceed to donation.
3- Exclude donors with BP 140/90 or above on 2 anti-hypertensive agents.
4- Exclude donors on more than 2 anti-hypertensive agents or with end organ damage.
Limitations:
1- Race of donors (higher non-Hispanic) was not reflecting the general population.
2- White coat hypertension was not ruled out by ABPM.
What is the level of evidence provided by this article?
Level III
Please reflect on the guidelines and refer to your practice.
In my center, all living donors with hypertension are excluded from donation.
Introduction
Hypertension was regarded as the second leading cause of ESKD. Evolving studies suggested that approximately third of kidney donors developed hypertension 15 years post donation. As well as the association of predonation hypertension in donors >50 years of age with increased probability of ESKD <1%.
Till now hypertension is known to advance the progression of established kidney disease, however this assumed link between hypertension and incident chronic kidney disease (CKD) is not accurately demonstrated. The SPRINT study stated that strict BP control did not lower the CKD incidence.
The study is concerned by the impact of isolated hypertension on long-term renal function in donors to aid in proper donor selection.
Methods
The Renal and Lung Living Donor Evaluation (RELIVE) study that involved 8922 living renal donors between 1963 and 2007 was the base of this project.
Hypertension was considered by the time of the study when BP exceeds 140/90 mm Hg or the use of antihypertensive agents. Postdonation hypertension was evident by the use of antihypertensive medications for treatment or a documented BP more than 140/90 mm Hg.
CVD included the occurrence of myocardial infarction, congestive heart failure, transient ischemic attack, stroke, or need for coronary or peripheral arterial intervention (angioplasty, stenting or bypass). Proteinuria detected by dipstick exceeded 2 +, urine protein/osmolality >0.42 ratio, urine random protein >15mg/dL or 24-h protein >300mg/day is considered.
Statistical Analysis
P < 0.05 was considered statistically significant.
Results
General Characteristics of Donors with Hypertension
In total, 6352 (72.8%) were involved among 8922 living renal donors had SBP <130 mm Hg, 1465 (16.8%) had 130< SBP < 140 mm Hg, 653 (7.5%) had SBP >140 mm Hg, and 251 (2.9%) were using antihypertensive agents.
Hypertensive donors (904) were older (48 vs. 38) years mostly non related men. They had significant increased weight, BMI, SBP, DBP, and a lower eGFR (83 vs. 89) ml/min/1.73 m2.
Unfortunately, 251 hypertensive donors received antihypertensive agents, 154 received monotherapy, 44 received dual therapy, 5 used triple therapy while in 43 donors this information was missing.
Hypertensive donors on treatment were average 7 years older than untreated ones, mostly non related white, besides displaying lower SBP and DBP at donation (133 vs. 145 mm Hg for SBP and 80 vs. 84 mm Hg for DBP).
Hypertensive donors on antihypertensive therapy also had a 10 ml/min/1.73 m2 lower baseline eGFR than hypertensive donors not receiving any treatment (P <0.001).
SBP was increasing by 2.2 mm Hg per decade (95% confidence interval [CI] 1.8–2.6) in non-hypertensive donors versus -0.3 mm Hg per decade (95% CI -1.6 to 1.1) in hypertensive donors.
The difference in slope was significantly different (P <0.001). DBP was higher by 1.1 mm Hg per decade (95% CI 0.8–1.3) in non-hypertensive donors versus -1.1 mm Hg per decade (95% CI -2.0 to 0.3) in hypertensive donors (P < 0.001).
Postdonation Hypertension Development
About 2319 donors developed hypertension 5.1+ 9.2 years post donation. These donors were younger at donation time (40 vs. 48 years of age). They were non- related to the recipient of higher baseline eGFR and lower BMI, as well as family history of HTN was free.
Postdonation hypertension development was linked to older age [aHR] 1.02 [95% CI 1.02–1.03]), male (aHR 1.31 [95% CI 1.19–1.44]), BMI (aHR 1.06 [95% CI 1.05–1.08]), and fasting plasma glucose (aHR 1.01 [95% CI 1.006–1.01]; P < 0.05 for all).
Outcomes of Interest at Last Follow-Up
After average from 17.6 to 10.7 years post donation to last follow-up in 2010 to 2012 in donors without hypertension , and about 14.3 to 10.1 years for donors with hypertension; it was found that ;
The proportion was similar regarding no mortality (4.7% vs. 6.0%, P = 0.09)
The incidence of CVD (12.7% vs. 13.9%, P= 0.31).
While the prevalence of DM (7.1% vs. 8.2%, P= 0.26).
The incidence of development of proteinuria was more in Hypertensive donors (17.8% vs. 13.4%, P < 0.001), these donors also had decline in eGFR < 60 and < 45 ml/min/1.73 m2.
Fortunately, the development of ESRD or decline of eGFR < 30 ml/min/1.73 m2 was estimated to be the same in both populations (6.6 [95% CI 4.8–9] vs. 10.9 [95% CI 4.5–75.2]) per 10,000 donor-years (P= 0.3).
The cases that developed ESRD were total of 44 persons, after a follow up period from 19.2 to 10.3 years post donation, 39 cases were known normotensive (0.5%) and only 5 cases were hypertensive donors (0.6%).
Hypertensive donors who developed ESRD were characterized by high BMI at donation and family history of HTN.
As demonstrated by this study, there was no ESRD incidence at all in HTN donors by 10 years post donation.
While the prevalence of ESRD by 30 years post donation was 51.8 (95% CI 27–99.6) per 10,000 donor-years in normotensive donors vs 61.5 (95% CI 8.7–436.6) in hypertensive donors (P=0.30).
Interestingly, decline of eGFR < 30 ml/min/1.73 m2 or ESRD was detected in 86 donors; 72 (0.9%) in normotensive donors and 14 (1.6%) in hypertensive donors.
Hypertensive donors showed evidence of higher serum creatinine level over time.
Multivariable Risks of Mortality, CVD, and ESRD
The main finding included that hypertensive donors were less prone to die or develop cardiovascular disease, or proteinuria or decline of eGFR, or even ESRD.
The aHR for occurrence of ESRD was 1.14 (95% CI 0.62–2.12, P=0.67.
The incidence of development of CVD associated with hypertension (aHR 1.34 [95% CI 1.05–1.51], P=0.02). It showed no comparable significance between both groups as the incidence of CVD in normotensive donors aHR 1.27 (95% CI 0.96–1.68, P=0.09).
Only 1465 donors matched the new definition of HTN (blood pressure exceeding 130/80 mm Hg). This subcategory only had comparable renal outcomes to non-hypertensive donors, as well as the probability of death (aHR 1.29 [95% CI 1.0–1.67], P=0.051), occurrence of CVD (aHR 1.36 [95% CI 1.15–1.61], P < 0.001), and even diabetes (aHR 1.41 [95% CI 1.08–1.83], P= 0.01).
The final conclusion is that, hypertensive donors compared to non-hypertensive donors in terms of decline of eGFR, proteinuria, ESRD, CVD or even death are not of increased risk except for those matching new definition of HTN ; they may develop CVD or DM.
The other conclusion is that one third of kidney donors may suffer HTN post donation.
The risk of ESRD in African American 3% may be not due to HTN, as hypertension itself may be related to CKD development owing to APOL1 polymorphism.
Holscher et al. claimed that renal donation had role in 19% higher risk of self-reported hypertension when compared to healthy non-donor control subjects. General population have typical SBP elevation by 7 mmHg normally.
This study found that SBP increased by 2.2 mm Hg per decade in normotensive donors at time of donation, which is evidently comparable to our previously described rate of 2.9 mm Hg per decade in a longitudinal study of 4296 renal donors between 1963 and 2014.
This study opens the gate for hypertensive donors to donate provided that BP is well controlled (assessed by ambulatory BP monitoring), no proteinuria and no end organ damage (no left ventricular hypertrophy or hypertensive retinopathy).
Strengths mainly include the large span of 50 year duration, different ethnicities. Addressing unusual different items in this study as GFR decline, serial serum creatinine, proteinuria assessment, CVD and DM.
Limitations may be the deficient exclusion of white coat hypertension, or normotensive donors having masked hypertension. Also, ESRD display low statistical as it is generally a less likely event rate to occur. Other unexplained issue is the surprisingly high eGFR in all donors.
The study finally sums up that white hypertensive donors have null risk of ESRD as a consequence of donation.
Level of evidence III.
Our centre accepts HTN donors exceeding 50 years, well controlled, after proper exclusion of any end organ damage.
We are very much immature till now we have done 44 KTx. We do accept donors with hypertension which is well control single antihypertensive and no end organ damage.
The limitations are no such shared blood pressure measurement, biased to take particular ethnicity.
poor performance of eGFR in those with GFR >60ml/minutes/m2, very wide range of follow up.
level of evidence III.
▪︎Introduction
Hypertension is well recognised leading cause of ESKD .
It was suggested that around one third of kidney donors developed hypertension 15 years after donation.
In many cases, hypertension follows the development of CKD rather than precedes it.
While definition of hypertension has changed
many kidney donors in the past would be considered hypertensive today.
follow-up of these donors allows good understanding of relationship between hypertension and kidney disease.
So this study was done to determine long term outcomes after donation in hypertensive and normotensive donors.
▪︎METHODS
8922 kidney donors from 3 U.S. transplant centers between 1963 and 2007 were included from RELIVE study to evaluate long-term outcomes of kidney donation.
Collected data included:
-previous or current diagnosis or treatment for hypertension or hyperlipidemia
-laboratory data.
– Family history of hypertension, diabetes mellitus, kidney disease, stroke, or heart disease.
-BP readings were collected on multiple occasions the average of the 3 lowest reading was used
*Hypertension was defined by the extant definition at the time if study which was BP >140/90 mm Hg or the requirement for antihypertensive agents.
Donors were contacted and were asked about developing diabetes, hypertension, kidney disease, CVD, cancer, and other conditions.
▪︎RESULTS
-median age at donation of the entire cohort was 39 years,
– 6352 had SBP <130 mm Hg, 1465 had < 140 mm Hg, 653 had SBP >140 mm Hg.
-251 were receiving antihypertensive medications.
-Hypertensive donors had a higher weight, BMI, SBP, DBP, and a lower eGFR (83 vs. 89 ml/min/1.73 m2).
-Hypertensive donors receiving treatment were on average 7 years older than untreated hypertensives, were more likely to be white, were less likely to be related to their recipient.
-hypertensive donors receiving antihypertensive medications had a 10 ml/min/1.73 m2 lower baseline eGFR than hypertensive donors not receiving treatmen
-2319 donors developed hypertension 5.1 to 9.2 years after donation.
– The development of postdonation hypertension was associated with older age , male gender.
▪︎Lone term follow-up for hypertensive and normotensive donors
– similar proportion were alive, had CVD , and had diabetes.
-Hypertensive donors were more likely to have proteinuria and eGFR < 60 and < 45 ml/min/1.73 m2 .
-the occurrence of eGFR < 30 ml/min/1.73 m2 or ESKD was similar in donors with and without hypertension.
-The overall ESKD incidence rate was similar in hypertensive and non-hypertensive donors .
-No cases of ESKD occurred in hypertensive donors in the first 10 years, and the incidence after 30 years was 51.8 per 10,000 donor-years in normotensive donors versus 61.5 in hypertensive donors.
▪︎ conclusion
hypertensive donors, compared with nonhypertensive donors, are not at increased risk for reduced eGFR, proteinuria, or ESKD.
roughly a third of kidney donors developed hypertension after donation.
What is the level of evidence provided by this article?
level Of evidence 3
Please reflect on the guidelines and refer to your practice.
donors with hypertension controlled on single agent without proteinuria are accepted after counselling about long-term outcomes
1-The aim of the study ;
—————————————-
Was to evaluate the outcome hypertensive kidney donors.
2-The type of the study;
—————————————
Retrospective cohort study.
3-The population
—————————————-
1-The study group; 904 hypertensive donors (blood pressure[BP] $140/90 mm Hg or receiving treatment) .
2- the controlled group; 7817 donors with BP <140/90 mm Hg.
4-The result;
————————-
1-At the end of follow-up, hypertensive and nonhypertensive donors had a similar prevalence of cardiovascular disease and renal outcomes.
2-The multivariable risk of mortality, CVD, and proteinuria were also comparable in normotensive and hypertensive donors.
3-eGFR slope over time was similar in hypertensive and non- hypertensive donors.
5-The strengths o the study ;
————————————————-
The population studied spans 50 years of kidney donation, is ethnically
diverse, and donors had ascertainable intermediate renal outcomes, such as reduced GFR, serial serum creatinine availability, proteinuria assessment, and CVD, which are not captured in national donor databases.
6-The limitations o the study ;
————————————————-
1-Donors included in this analysis come from 3 major U.S. transplant centers with a longstanding tradition in live kidney donation and while ethnically diverse, the proportion of non-Hispanic white donors in the RELIVE study was significantly higher than what is observed in the larger U.S. donor pool, which is approximately 70%. Moreover, the proportion of Hispanic and Asian donors were less than what is observed nationally.
2-There probably was no standardization of how BP measurements were carried out at the 3 centers, and many donors labeled as hypertensive may have simply had white coat hypertension.
Conclusion;
————————-
1-In all, these data show that predominantly non- Hispanic white hypertensive donors do not have an increased risk of ESKD compared with normotensive kidney donors.
2- Importantly, the more common events of eGFR change after donation and proteinuria development were also similar between hypertensive and normotensive donors.
3-The study suggests that, most donor candidates with hypertension, particularly white donors, can be considered for donation provided that subtle renal disease is ruled out and the hypertensive candidate is not at a magnified risk for future CVD from hypertension presence on the background of other risk factors.
.
What is the level of evidence provided by this article?
—————————————————————————–
Level III
Please reflect on the guidelines and refer to your practice.
————————————————————————————
We exclude hypertensive donors using more than 2 anti hypertensive agent .
· A recent study found that one third of kidney donors developed HTN after 15 years of donation, while only <10% of non-donors control group had HTN
· Pre-donation hypertension in donors >50 years of age was associated with an overall ESKD incidence of <1%
· In many cases, hypertension follows the development of CKD rather than precedes it.
· Strict BP control in the SPRINT study, did not appear to lower CKD incidence, while it lowers mortality
· Data obtained from the (RELIVE) study, that evaluated outcomes of 8922 kidney donors from 3 U.S. transplant centers
· All donations took place between 1963 and 2007
· Donors were contacted by mail requesting participation in the RELIVE study
· a follow-up letter and 2 phone calls or more were made by study personnel, in case of no response to the mail
· Definitions:
1- Postdonation hypertension: use of antihypertensive medications or a documented home, center, or office-based BP >or =140/90 mm Hg.
2- CVD: myocardial infarction, congestive heart failure, stroke, or the need for coronary or peripheral arterial interventions.
3- Proteinuria any of the following: urine dipstick protein $2þ, urine protein/ osmolality ratio >0.42, urine random protein >15 mg/ dl, or 24-hour protein >300 mg/day
4- ESKD: the need for dialysis or being listed for or receiving a transplant
Results:
· Hypertensive donors were older and had a lower eGFR.
· The majority were white and related to their recipient.
· At the end of follow-up, (range 4–48 years) from donation, hypertensive and non-hypertensive donors had a similar prevalence of CVD and renal outcomes.
· The multivariable risk of mortality, CVD, and proteinuria were also comparable in normotensive and hypertensive donors.
· eGFR slope over time was similar in hypertensive and non-hypertensive donors, and in total 5 hypertensive and 39 normotensive donors developed ESKD
· Sensitivity analysis using the new definition of hypertension (>or=130/80 mm Hg or requiring treatment) yielded similar results for renal outcomes,
· hypertensive donors were more likely to develop CVD and diabetes.
Conclusions:
· Kidney donors with hypertension defined by past criteria didn’t have higher mortality, CVD, or ESKD.
· Donors with current definition of hypertension had the same renal outcomes but were more likely to develop CVD.
The strength of the study
· Long study span enabled them to detect the change in GFR and CVD.
Limitations:
· the proportion of non-Hispanic white donors in the RELIVE study was significantly higher than what is observed in the larger U.S. donor pool, which is approximately 70%.
· the proportion of Hispanic and Asian donors were less than what is observed nationally.
· The RELIVE study public dataset does not have the cause of ESKD in donors
· It is unknown if BP measurements were done with the same way at the 3 centers, and many donors diagnosed as hypertensive could have white coat hypertension
· Many normotensive donors, may have had masked hypertension
What is the level of evidence provided by this article?
Retrospective cohort study, evidence 3
Please reflect on the guidelines and refer to your practice.
We used to exclude hypertensive donors. But now, if the patient has no proteinuria, no cardiac muscle hypertrophy, and BP controlled not on more than 2 drugs, I will accept the donor
1. Please summarise this article in your own words
Reduced renal mass is known to predispose to hypertension.
It is estimated to develop in 1/3rd of the kidney donors in 15years, while in less than 1/10th non donors.
Hypertension is the second most common cause of ESRD in USA and soe other countries.
Hypertension is known to accelerate CKD.
Most transplant program exclude hypertensive donors.
Definition of hypertension has been changed over time, from >140/90 to >130/80 recently. This means that many donors in the past would be considered hypertensive with current criteria, allowing for studding isolated hypertension outcome.
Methods
Retrospective study of donors from the Renal and
Lung Living Donor Evaluation (RELIVE) study between1963-2007 in 3 USA centers.
Donors were contacted by emails to participate in the study.
Qol questionnaire was given to donors to fill.
If no response, phone calls, follow up date from their centers, and information from corresponding recipients were taken.
Results
Out of 8922, 8721 responded and have their blood pressure measurement available. Blood pressure records were reviewed, and the average of 3 lowest reading was taken.
Majority donated to their relatives.
71% has ≥1 first degree relative affected by kidney disease.
41% has ≥1 first degree relative with hypertension.
16.8% has SBP between 130-140, 7.5& SBP >140 and 2.9% on antihypertensive medications.
Hypertensive and non hypertensive have similar cardiovascular and renal disease. Also mortality and proteinuria were not affected.
Conclusion:
Previous donors with hypertension defined by previous criteria have no increased risk of cardiovascular or renal disease, but if we used current definition risk of cardiovascular disease will increase.
2. What is the level of evidence provided by this article?
Level 3
3. Please reflect on the guidelines and refer to your practice.
In our center we exclude hypertensive donors. After this we may consider them after making sure no hypertension complications and consent both recipient and donors.
Please summarise this article in your own words
Donors with hypertension have higher risk of cardiovascular disease and CKD/ESRD. Usually such donors are not accepted for donation and the figure is about 50 % in US.
This retrospective study looked at the following variables among donors with hypertension ( BP >140/90 mmHg) and those with BP < 140/90 mmHg .
Donors with Hypertension- 904
Donors with BP < 140/90 mm Hg-7817
Variables checked-
CVD
Proteinuria
GFR trajectory
Mortality
reduced eGFR
Results-
About one third developed hypertension and risk factors were High BMI, Male gender, older age. Majority of donors who had hypertension were male and white with higher age.
Not much difference between both groups as regards renal outcome but Cardiovascular morbidity was higher in hypertensive with new definition 130/80 mmhg
Using old definition ( BP >140/80 mm Hg) – No differences was noted as regards mortality ,proteinuria , ESRD,CKD
Conclusion.
Kidney donation using old definition of hypertension does not appear to cause high mortality, CVD risk/ESRD
Using new definition the outcomes are similar but higher CVD
What is the level of evidence provided by this article?
Retrospective study Level 111.
Please reflect on the guidelines and refer to your practice.
In my centre hypertensive donors are excluded. By reviewing this article, those with hypertension as per new definition with sign of end organ damage can be considered for donation after proper education and counselling. They should be explained about higher cardiovascular risks
Abstract:
Reductions in renal mass and function are associated with an increase in blood pressure
and the development of systemic hypertension.
The definition of hypertension has evolved over the years, and therefore many kidney
donors who donated in the past, particularly early on in transplantation history, would be
considered hypertensive by today’s standards.
This provides a unique opportunity to study the impact of isolated hypertension on long-
term kidney function because donors have no evidence of any renal involvement, such
as proteinuria or low GFR, and no major comorbidities at donation, and therefore the
temporal relationship between hypertension and kidney disease can be better dissected.
METHODS:
data from The Renal and Lung Living Donor Evaluation (RELIVE) study.
Study population:
8922 kidney donors from three U.S. transplant centers.
Results:
653 (7.5%) had SBP $140 mm Hg, and 251 (2.9%) were receiving antihypertensive
medications.
General Characteristics of Donors with Hypertension:
Hypertensive donors (n ¼ 904) were older (48 vs. 38 years), more likely to be men, less
likely to be related to the recipient, and more likely to have a college education.
Hypertensive donors had a higher weight, BMI, SBP, DBP, and a lower eGFR (83 vs. 89-
ml/min/1.73 m2)
Outcome:
. Hypertensive donors were more likely to have proteinuria (17.8% vs. 13.4%, P < 0.001)
and more likely to have an eGFR < 60 and < 45 ml/min/1.73 m2. However, the
occurrence of eGFR < 30 ml/min/1.73 m2 or ESKD was similar in donors with and
without hypertension.
Conclusion:
Multivariable Risks of Mortality, CVD, and ESKD After adjustment for baseline laboratory
values, demographic factors, and the development of diabetes and hypertension after
donation, we found that hypertensive donors were not more likely to die, develop
cardiovascular disease, develop proteinuria, have a reduced eGFR, or have ESKD.
Donors fulfilling the new definition, however, were more likely to develop CVD and
diabetes. These results also show that roughly a third of kidney donors developed
hypertension after donation.
Most donor candidates with hypertension, particularly white donors can be considered
for donation if subtle renal disease is ruled out and the hypertensive candidate is not at a
magnified risk for future CVD from hypertension presence on the background of other
risk factors.
Limitation:
Public dataset does not have the cause of ESKD in donors.
No standardization of how BP measurements were carried out at the three centers.
Non-Hispanic white donors in the RELIVE study was significantly higher.
Level of evidence 111
Patient with good controlled hypertension on two medication and no evidence of target
organ damage can donate.
Definition of hypertension has always been a matter of debate. Changing the cut off of BP for labelling hypertension affects various treatment protocols.
Similarly, The outcomes of hypertensive living kidney donors also gets modified by changing the definitions of hypertensions.
The current study tries to evaluate the same with respect to mortality, CVD, proteinuria, eGFR and ESRD.
The follow up period in the study ranges from 4 to 48 years.
This study tries to determine outcomes of donors using the newly
introduced hypertension definition of hypertension of > 130/80 mm Hg.
METHODS
data was extracted from RELIEVE study. No fresh recruitment was done.
Data was analyzed using Pearson’s and Fischer exact test.
RESULTS
Level of evidence is 3
We are not accepting donation from hypertensive donors as per our institutional transplant policy
Kidney disease has been an ongoing issue due to cost and insufficient donors. The donor pool worldwide is limited to the number of patients with kidney failure. The most frequent cause of kidney failure is hypertension and even during the donation process and post-transplantation the living donors may develop hypertension. In the US, hypertension is a contraindication for kidney donation, and almost 50% of centers do not accept living donors with HTN. The question was raised if kidneys with HNT can be used as a donor and as such, they used a study from the RELIVE with a population of 8922 kidney donors from 3 different centers of transplantation for the US. The study took a period between 1963-2007. With the different definitions of HTN the one used was a blood pressure greater than 140/90 mmHg and or requires antihypertensive.
To have a clear understanding of post-transplantation hypertension, it was defined as having antihypertensive medications once pressure is elevated to 140/90 mmHg. The level of proteinuria used varies from the methods used like urine dipstick of 2 plus protein, random protein is about 15 mg/dl and a 24 hours protein is about 300 mg/day. Cardiovascular pathology includes all pathology that is in the systems like MI, CCF, ETC.
From the population of 9822, about 8721 had pre-donation vitals taken like their blood pressure. From that total, about 72.8% had BP less than 130 mmHg, 16.8 percent had blood pressure less than 140 mmHg and 7.5 % had blood pressure greater or equal to 140 mmHg and were on medications.
Living donors with hypertension were found in older patients and most were the male sex. It was noted that the BMI, systolic and diastolic BP, and a lower GFR were found higher in hypertensive donors. Depending on the level of the BP, antihypertensive was given from one to 5 drugs.
So one can deduce that the major risk factors to develop elevated BP post donation are older age, male sex, etc. It was noted that about a third of donors after donation gradually develop HTN. It was found that cardiovascular disease was found to be very common in the groups. Kidney failure was not significant between the non-HTN and the HTN groups.
The major limitation of this study was the population it was focused on that is the white race and never include other groups.
So, in conclusion, one can see that HTN donors and non-HTN donors are not at risk of reduced GFR proteinuria or ESRD and thought. Also, living kidney donors develop hypertension. The newer definition of HTN was more likely to have complications like proteinuria, CVD, and DM.
The level of evidence for this article is level 3
In my practice since still unable to have one but looking in the future to do so may want to exclude donors with elevated BP and taking more than one drug due to future kidney complications post-transplantation. Proper follow-ups are essential.
Organ shortage is a worldwide problem in kidney transplant programs.Hypertension is considered a contraindication for donation and almost as 50% of U.S. transplant centers do not accept kidney donor candidates with hypertension, citing the link between hypertension, kidney disease, and cardiovascular disease (CVD).
Ibrahim and collaegues have tried to answer the question that if hypertensive patients can become safe donors.
They used publicly available data from The Renal and Lung Living Donor Evaluation (RELIVE) study that evaluated outcomes of 8922 kidney donors from 3 U.S. transplant centers:
the University of Minnesota,
Mayo Clinic-Rochester,
and the University of Alabama-Birmingham.
All donations took place between 1963 and 2007.
Hypertension was defined by the extant definition at the time of the study, which was BP 140/90 mm Hg or the requirement for antihypertensive agents.
Postdonation hypertension was defined as use of antihypertensive medications specifically used for hypertension treatment or a documented home, center, or office based BP 140/90 mm Hg. CVD was defined as a diagnosis of myocardial infarction, congestive heart failure, stroke, or the need for coronary or peripheral arterial interventions. Proteinuria was defined as any of the following: urine dipstick protein 2++ urine protein/ osmolality ratio >0.42, urine random protein >15 mg/ dl, or 24-hour protein >300 mg/day.
Of 8922 kidney donors, 8721 donated a kidney between 1963 and 2007, had multiple predonation BP measure- ments available, and had their vital statuses ascertained
The median age at donation of the entire cohort was 39 years, 56.2% were women, 85% were non-Hispanic white, 9.2% were non-Hispanic black, 1.8% were Hispanic, 0.9% were Asian, and 3% were categorized as other.
In total, 6352 (72.8%) had SBP <130 mm Hg,
1465 (16.8%) had 130 SBP < 140 mm Hg,
653 (7.5%) had SBP more than or equal to 140 mm Hg, and 251 (2.9%) were receiving antihypertensive medications.
Hypertensive donors (n 904) were older (48 vs. 38 years),
more likely to be men
less likely to be related to the recipient
and more likely to have a college education. Hypertensive donors had a higher weight, BMI, SBP, DBP, and a lower eGFR (83 vs. 89 ml/min/1.73 m2).
Of the 251 hypertensive donors receiving antihypertensive medications, 154 received 1 agent
44 received 2
5 used 3 agents
and in 43 donors this information was missing.
Postdonation Hypertension Development
An additional 2319 donors developed hypertension 5.1 ! 9.2 years after donation
Predominantly non- Hispanic white hypertensive donors do not have an increased risk of ESKD compared with normotensive kidney donors. Importantly, the more common events of eGFR change after donation and proteinuria develop- ment were also similar between hypertensive and normotensive donors. The authors believe that most donor candidates with hypertension, particularly white donors, can be considered for donation provided that subtle renal dis- ease is ruled out and the hypertensive candidate is not at a magni”ed risk for future CVD from hypertension presence on the background of other risk factors.
Level three evidence . Observational retrospective study
We at our centers do accept hypertensive donors if there BP is well controlled on two antihypertensive meds without any evidence of target organ damage so this paper is not going to have an impact on our practice style.
P
Hypertension has link with kidney disease and cardiovascular disease. Hence many transplant centres reject donors with hypertension.
The study involved comparing outcomes of donors (from 1963-2007) with hypertension (904 in number) with matched donors with BP <140/90 (7817 in number) with respect to development of proteinuria, cardiovascular disease (CVD), mortality, reduced eGFR, ESRD and trajectory of fall in GFR for a mean follow-up of 14.3±10.1 years. It was done from the dataset of RELIVE study involving 3 transplant centres in USA using live donors. The donors were contacted between 2010 and 2012.
The donors with hypertension were older, more whites and males, 73% were related to the recipient (lower percentage than normotensives), and had lower baseline GFR. The follow-up was shorter in case of hypertensive group. The hypertensive group had increased incidence of first degree relative with hypertension and had higher body weight and BMI.
Among the hypertensives, 651 had BP>140/90 while 251 were on antihypertensives. Those on antihypertensives had higher BMI, higher fasting blood sugars, lower SBP and lower GFR than those with BP>140/90.
2319 donors developed hypertension post-donation. This group had a longer follow-up, lower mean age with a higher number having a relative with kidney disease and higher GFR at baseline.
The prevalence of CVD and renal outcomes were similar to the non-hypertensive group. There was no difference between the 2 groups with respect to development of proteinuria, CVD, mortality as well as the rate of fall of GFR over time. Among the hypertensive group, the incidence of fall in GFR to <60 and <45 ml/min was more as compared to that in the non-hypertensive group. But there was no difference in the groups with respect to development of ESRD.
Even when the definition of hypertension was changed to BP>130/80, there was no difference in the 2 groups except increased risk of CVD and diabetes in the group with BP>130/80.
This study concludes that kidney donors with previous criteria (BP>140/90) had results similar to those with BP<140/90 with respect to CVD, ESRD or mortality. The change of hypertension definition (to BP>130) increases the risk of CVD in hypertensive group, but the renal outcomes remain similar.
The strengths of the study include long time span (>50 years) of kidney donation, diverse study population, use of quantifiable markers like serum creatinine, GFR, proteinuria etc.
The limitations of the study include disproportional distribution of ethnicity in the study population with respect to the general population, lack of data regarding etiology of ESRD in the recipients, lack of data regarding outcome of hypertensive donor’s kidney in the recipient, and lack of data regarding method of measurement of BP in the 3 centres (whether it was standardized or not).
2. What is the level of evidence provided by this article?
Level of evidence: Level 3 – retrospective cohort study
3. Please reflect on the guidelines and refer to your practice.
In our transplant unit, we consider hypertensive donors if they have well controlled blood pressure on maximum 2 antihypertensives and there is absence of any target organ damage.
Post-donation, they are advised to maintain a healthy lifestyle, keep BP under control and to remain under regular follow-up.
This is a retrospective observational cohort study with three US centers collecting data between 1963 and 2007 (Level of Evidence 2b). The objective is to evaluate the evolution of hypertension in patients who became living kidney donors. There are questions about development of hypertension, cardiovascular disease, proteinuria, and eGFR reduction.
The concept of arterial hypertension changed in the period, but in order not to avoid conflicting data, those with blood pressure greater than 140x90mmHg or using antihypertensive medications were defined as hypertensive. Diabetes mellitus was considered with fasting glucose greater than 126 or with suggestive target organ damage or the addition of hypoglycemic medications.
8922 donors in the period, 201 were excluded due to lack of data and separated into two groups (7817 without SAH and 904 with hypertension). The hypertensive group is seven years older than the control group (aHR 1.02), tends to be Caucasian, male (aHR 1.31), has higher BMI (aHR 1.06), higher glucose (aHR 1.01), and lower eGFR.
The development of ESKD in hypertensive donors was associated with BMI in the donation and hypertensive first-degree relatives. They have historically higher serum creatinine but no eGFR changes.
The study’s conclusion suggests that hypertensive donors have no additional risk of reduced eGFR, proteinuria, or ESKD, but are more likely to be diabetic and have cardiovascular events. The study proposes that hypertensive donors may be eligible for donation as long as they have blood pressure control, and do not have proteinuria or damage to target organs.
It is a 50-year-old, ethnically diverse study (despite nearly 70% being Caucasian).
Summary:
· Hypertension is one of most common causes for declining potential living kidney donors.
· Assessment of hypertensive complications as regard CKD progression, mortality and CVS mortality was the aim of the current study, by comparing hypertensive and none hypertensive donors after 14 years of follow up.
· The difference between old and current studies is in the definition of hypertension, the old def is >140/90 mmHg, while the new def is > 130/80.
· Using the current def of HTN > 130/80 made the outcome of hypertensive donors worse as regard CVS mortality.
· So, application of the new def on the previous donors in the era of old definition, helps to identify the effect of isolated hypertension on those donors’ outcomes.
· Hypertension leads to CKD progression either by hypertensive nephrosclerosis or associated FSGS.
· The old def when used, both hypertensive and none hypertensive donors had similar outcomes as regard HTN, proteinuria, CKD and CVS disease.
· The applied new def was associated with cardiovascular risk in hypertensive donors when compared to none hypertensive ones.
· Limitations of the current study:
o Involvement of 3 different centers with diverse ethnic groups, different approaches to donation accepted criteria and none standardized measurement of blood pressure.
Level of evidence: retrospective cohort (III).
Reflect on your practice:
– We are still strict to the guideline that only accepted donors must have ABP <140/90 with one or 2 antihypertensive medications with ensuring that no target organ damage as retinopathy, nephropathy or LVH.
– Counseling regard weight loss, control of weight, salt intake, smoking cessation and regular monitoring of ABP post donation.
– I think reflection on our practice, to be strict to the new definition of hypertension > 130/80.
Outcomes of Hypertensive Kidney Donors Using Current and Past Hypertension Dentitions
Kidney International Reports (2021)
There is no unanimous agreement regarding the definition of HTN, measurement method, cutoff to start treatment, and best drug of choice for each specific subgroup, therefore many kidney donors were accepted as potential donors in the past, and they could be considered as hypertensive as per some centers and some societies guidelines.
This is a retrospective Cohort study (evidence IIIa) evaluating the impact of isolated HTN on mortality, GFR assessment, development of proteinuria, ESRD, and CVD as regards old and new cutoff of hypertension diagnosis.
Methods
Setting: RELIVE study (3 centers in the US)
Population: This study included 8922 donors (1963-2007) from which only 8721 donors had documented blood measurement (average of 3 least BP reading used as baseline BP pre-donation): 904 kidney donors with BP ≥140/90
Control group: 7817 donors with BP <140/90 mm Hg over a period of
Follow up duration:14.3 ± 10.1 years
As regards: Control regarding mortality, GFR assessment, development of proteinuria, ESRD, and CVD
Results
Limitations:
Conclusions:
Please reflect on the guidelines and refer to your practice:
Guidelines
Although HBP and 24 ABP are the most accurate and more related to all morbidities and mortality still office BP is the most used as regards diagnosis of hypertension
All potential donors with office BP 3 reading more than 140/90 should be evaluated with HBP or 24H ABP
If HBP or 24H ABP is still more than 140/90 donor is now diagnosed as a hypertensive patient and should be evaluated as regard end organ damage
If there is any evidence of end-organ damage (LVH, retinopathy, normal eGFR, and no proteinuria) he should be excluded from donation
If there is no evidence of end-organ damage and bp is controlled with one or two antihypertensive medications. He can be considered a potential donor.
Our center practices:
We only accept nonhypertensive donors based on 3 different office BP measurement
A hypertensive potential donor who has controlled over 1 or 2 medications with or without organ damage we exclude from donation
Please summarise this article in your own words
-Reductions in renal mass and function are associated with an increase in blood pressure and the development of systemic hypertension in animal models and humans with reduced renal mass.
-Predonation hypertension in donors >50 years of age was associated with an overall ESKD incidence of <1%.
– The study used publicly available data from The Renal and
Lung Living Donor Evaluation (RELIVE) study.General Characteristics of RELIVE Study Donors Of 8922 kidney donors, 8721 donated a kidney between 1963 and 2007, had multiple predonation BP measurements available, and had their vital statuses ascertained
– The development of postdonation hypertension was associated with older age , male gender , BMI , and high fasting plasma glucose .
-Hypertensive donors were more likely to have proteinuria and more likely to have an eGFR < 60 and < 45 ml/min/1.73 m2. However, the occurrence of eGFR < 30 ml/min/1.73 m2 or ESKD was similar in donors with and without hypertension.
– The development of ESKD in hypertensive donors was associated with BMI at donation and having a firstdegree relative with hypertension.
-The overall ESKD incidence rate was similar in hypertensive and nonhypertensive
donors .
– Hypertensive donors had a significantly higher serum creatinine level over time, but eGFR trajectory was comparable in donors with and without
hypertension .
-After adjustment for baseline laboratory values, demographic factors, and the development of diabetes and hypertension after donation,they found that hypertensive donors were not more likely to die, develop cardiovascular disease, develop proteinuria, have a reduced eGFR, or have ESKD.
-Hypertensive donors were not more likely to develop the composite of eGFR < 30 ml/min/1.73 m2 or ESKD.
-Donors who Fulfilled the more recent definition of hypertension(˃ 130/80
mm Hg) had comparable renal outcomes to nonhypertensive donors
but were more likely to die , were more likely to develop CVD, and were
more likely to develop diabetes .
-In conclusion, the results suggest that hypertensive donors, compared with nonhypertensive donors, are not at increased risk for reduced eGFR, proteinuria, or ESKD. Hypertensive donors by previous definition were not more likely to die or develop CVD, either. Donors fulfilling’s the new definition, however, were
more likely to develop CVD and diabetes.
-The strengths :The population studied spans 50 years of kidney donation, is ethnically diverse, and donors had ascertainable intermediate renal outcomes, such as reduced GFR, serial serum creatinine availability, proteinuria assessment, and CVD, which are not captured in national donor databases.
-The limitations, however. Donors included in this analysis come from 3 major U.S. transplant centers with a longstanding tradition in live kidney donation and while ethnically diverse, the proportion of non-Hispanic white
donors in the RELIVE study was significantly higher than what is observed in the larger U.S. donor pool, which is approximately 70%. Moreover, the proportion
of Hispanic and Asian donors were less than what is observed nationally. The RELIVE study public dataset does not have the cause of ESKD in donors and it would also have been ideal to know how kidneys from hypertensive
donors fared in the recipients.
– Importantly, there probably was no standardization of how BP measurements
were carried out at the 3 centers, and manydonors labeled as hypertensive may have simply had white coat hypertension. To at least partially address the latter, the average of the 3 lowest BP measurements were used as baseline. Many normotensive donors, on the other hand, may have had masked hypertension, which is also not captured.
What is the level of evidence provided by this article?
Level 3
Please reflect on the guidelines and refer to your practice.
-Donor candidates with hypertension, can be considered for donation provided that subtle renal disease is ruled out and other risk factors of CV
Summary
Introduction
Hypertension can be the result of kidney disease and also the cause of progression to ESRD, due to the progressive ischemic effect on the renal mass which has been confirmed by animal and human studies, and the majority of kidney transplant programs consider hypertension as one of the exclusion criteria for donation as hypertension is the second leading cause of ESKD including post donation hypertension in one-third of donors after 15 years of Follow up however it’s associated with < 1% risk of ESRD the definition of hypertension have been reformed over years and many of old donors now would be considered hypertensive donors based on the new definition. And this will offer us a good chance to study the isolated hypertension risk in otherwise healthy donors’ on long-term follow-up and the association between hypertension and the risk of progressive CKD as an outcome this will help to reframe our donor selection criteria and determine the outcome of donors based on the new hypertension definition criteria.
Aim
1. Study the effect of isolated hypertension on long-term kidney function as an outcome
2. Determined the relationship between donor hypertension and kidney disease
3. Study the outcome of the donors based on a new definition of hypertension (>130/80 mmHg or need treatment)
Method
This study from 3 US centers data collected from the national database from The Renal and Lung Living Donor Evaluation (RELIVE) study from 1963-2007, includes> 8922 donors and 8721 donated a kidney between1963 and 2007, had multiple pre-donation BP measure and vitals available in 99.8% .all data recorded from each center including donors’ demographics, clinical characteristics, family history of HTN, DM CKD, Bp measurement in 3 occasions and as per the extant definition at the time of the study, which was BP >140/90 mm Hg or the requirement for antihypertensive agents, between 2010-2012 the data sources were based on personal records through communication by phone, emails, and an internet connection, including quality of life surveys in addition to the recipient’s information about their donors. So most of the FU records about DM, HTN, CVD it’s by self-reporting by the donors, proteinuria defined as urine dipstick protein >2þ, urine protein/osmolality ratio >0.42, urine random protein >15 mg/ dl, or 24-hour protein >300 mg/day.ESKD is defined as the need of dialysis or listed for kidney transplant waiting .
The new definition of hypertension (>130/80 mm Hg or requiring treatment)
Results
Regarding baseline patients’ demographics and clinical characteristics as shown in table 1, hypertensive donor 907 from > 8721
Hypertensive donors were older with positive FH of hypertension and CKD compared to non-hypertensive Living related donors, the majority are white and 58% of donors are < 50 years old
Lower baseline GFR in hypertensive donors with higher baseline line, Systolic and diastolic BP, serum creatinine, BMI, and higher fasting glucose compared to non-hypertensive donors
Hypertensive donors were more likely to have proteinuria
(17.8% vs. 13.4%, P < 0.001) and more likely to have an eGFR < 60 and < 45 ml/min/1.73 m2 However, the occurrence of eGFR < 30 ml/min/1.73 m2 or ESKD was
similar in donors with and without hypertension
In the new definition of hypertension, only hypertensive donors are more prone to CVD and DM with similar renal outcomes.
2319 Donors developed hypertension on average 5 plus 9 years post-donation and they were younger at the age of donation and fewer related to the recipients had lower BMI,
1462 Donors who fulfilled the more recent classification of hypertension had equal renal outcomes to non-hypertensive donors
but were more likely to die from CVD and also more BMI and DM.
This study confirms no difference between hypertensive and non-hypertensive donors and the risk of CKD, or CVD up on follow-up time including the multivariable risk of mortality, CVD, and proteinuria, change in the e GFR slope also similar between the two groups
limitation of this study
Selection bias, more white population, self-reporting of the data
Standardization of BP monitoring from the three different centers so may mask with whitecoat BP
Poor GFR estimation performance modules over fu time
The primary disease of ESRD in the recipients was not identified which may can contribute to the renal outcome, especially in related donors.
based on this study i will bemore caution in dealing with donors’ LRD and focus on age gender ,and ethnic background and associated metabolic factors like BMI , impaired fasting ,FH of CKD not only isolated hypertension but also the use of ABPM for the diagnosis of hypertension , hyperuricemia
According to this ,all patient with HTN and no end organ damage with 1 to 2 anti HTN agent can be accepted for donation .
one of the limitation that many centers involved with out knowing how BP was mesuered
Please summarise this article in your own words
Hypertension is the second leading cause of ESRD, this is due to decresed renal mass and function.
It was suggested that 30% of donors will develop HTN in comparison to 10% in non donors healthy controls.
The definition of hypertension has changed over time from =/>140/90 mmHg to =/>130/80 mmHg, so old donors were considered normotinsive but they are hypertensive according to new guidelines.
Study design:
8922 kidney donors from 1963-2007, were collected from RELIVE study, in three centers, 7817 donors were normotensive, and 904 were HTN, with a mean follow up of 14.3+/-10.1 years., data collection from 2010-2012 period.
The family history for HTN, DM, kidney disease, stroke, or heart disease in all donors was reported.
B/P >140/90 mmHg considered as hypertension- taken in multiple occasions – the lowest reading were taken as baseline blood pressure to eliminate the possibility of white coat HTN.
ESKD was defined by need for dialysis, or receiving or being listed for a kidney transplant.
CVD defined defined by any myocardial infarction, congestive heart failure, transient ischemic attack, stroke, or need for coronary or peripheral arterial intervention.
Proteinuria defined as one or more of the following: urine protein by dipstick >+2, urine protein/osmolality >0.42 ratio, urine random protein >15 mg/dL or 24-h protein >300 mg/day.
Two analysis were collected, first according to B/P =/> 140/90 mmHg (old definition), second according to B/P =/>130/80 mmHg.
Results:
Hypertensive donors were older, more likely to be men, less likely to be related to the recipient, and more likely to have a college education.
Hypertensive donors had a higher weight, BMI, SBP, DBP, and a lower eGFR(83vs89), 251 of them were receiving one or more anti hypertensive medication and were in average 7 years elder than untreated ones.
Donors with postdonation hypertension were younger at donation, less likely to be related to the recipient, had a higher baseline eGFR, a lower BMI, and were less likely to have a first-degree relative with hypertension.
post-donation HTN more in older patients , males, higher BMI, and fasting plasma glucose level.
= Hypertensive donors were more likely to have proteinuria (P < 0.001) and more likely to have an eGFR < 60 and < 45 ml/min/1.73 m2 , but no increased risk of ESKD (increased in donors with first degree relative with HTN, and high BMI).
= Hypertensive donors had a significantly higher serum creatinine level over time, but eGFR trajectory was comparable in donors with and without hypertension.
= Donors who fulfilled the more recent definition of hypertension had comparable renal outcomes to nonhypertensive donors but were more likely to die (P= 0.051), were more likely to develop CVD (P < 0.001), and were more likely to develop diabetes (P = 0.01).
= Hypertensive donors, compared with nonhypertensive donors, are not at increased risk for reduced eGFR, proteinuria, or ESKD, but according to recent criteria for HTN they were more to have CVD and to develop diabetes.
Strength of the study:
The population studied in 50 years of kidney donation, with ethnic diverse, and ascertained intermediate renal outcomes, such as reduced GFR, serial serum creatinine availability, proteinuria assessment, and CVD, which are not captured in national donor databases.
Limitations of the study:
= The study conducted from 3 transplant centers donors, which differ in ethnic group than the population in RELIVE.
= No standardized method to monitor B/P among the three centers, the lowest reading of three B/P reading considered baseline B/P, not identifying the masked HTN.
= Poor performance of eGFR estimating models in those with GFR >60 ml/min and the fact that the serum creatinine assay has certainly changed over the almost 5 decades of the RELIVE study.
Conclusion:
Kidney donors with hypertension defined by past criteria do not appear to incur higher mortality, CVD, or ESKD.
Donors with current definition of hypertension enjoyed similar renal outcomes but were more likely to develop CVD, and DM.
Donor candidates with hypertension, particularly white donors, can be considered for donation provided that subtle renal disease is ruled out.
What is the level of evidence provided by this article?
Level of evidence III– retrospective cohort outcome study.
Please reflect on the guidelines and refer to your practice.
In our practice we still consider B/P=/> 140/90 mmHg as having HTN, we also perform full work up evaluating the renal function including urinary protein by 24 hrs creatinine clearance and protein, in patients mentioned any high blood pressure events out of the clinic and those whom had high blood pressure reading at clinic visits- while denying high B/P at home we use to perform ABPM, in order to identify white coat or masked HTN.
We can accept patients controlled with one antihypertensive agent, but not on more, from this study we can consider even those controlled with two drugs, in order to increase donor pool.
Reductions in renal mass and function are associated with an increase in blood pressure and the development of systemic hypertension in animal models and humans with reduced renal mass. 1,2 Hypertension is widely cited as the second leading cause of ESKD in the United States, and ESKD in many former kidney donors has been attributed to hypertension.3,4 Moreover, a recent analysis suggests that roughly a third of kidney donors developed hypertension 15 years after donation compared with <10% in nondonor healthy control subjects, and in a separate analysis from the same investigators, predonation hypertension in donors >50 years of age was associated with an overall ESKD incidence of <1%. 5,6 The kidney- and cardiovascular-related concerns regarding hypertensive candidates are reflected by exclusions and also restrictions put on donor candidates with hypertension by many transplant centers.
The definition of hypertension has evolved over the years, and therefore many kidney donors who donated in the past, particularly early on in transplantation history, would be considered hypertensive by today’s standards. This provides a unique opportunity to study the impact of isolated hypertension on long-term kidney function because donors have no evidence of any renal involvement, such as proteinuria or low GFR, and no major comorbidities at donation, and therefore the temporal relationship between hypertension and kidney disease can be better dissected. Moreover, such knowledge may also inform our current selection criteria pertaining to donor candidates with hypertension. Lastly, determining outcomes of donors using the newly introduced hypertension definition (>=130/80 mm Hg) would shed light on the size of the overall kidney donor pool if centers were to use it for donor eligibility.
Results: Hypertensive donors were older, 58.1% were <50 years of age, and they had a lower eGFR. The majority were white and related to their recipient. At the end of follow-up, 14.3 Æ 10.1 years (range 4–48 years) from donation, hypertensive and nonhypertensive donors had a similar prevalence of cardiovascular disease and renal outcomes. The multivariable risk of mortality, CVD, and proteinuria were also comparable in normotensive and hypertensive donors. eGFR slope over time was similar in hypertensive and nonhypertensive donors, and in total 5 hypertensive and 39 normotensive donors developed ESKD 19.2 Æ 10.3 years after donation (adjusted hazard ratio 1.14 [95% confidence interval 0.62–2.12], P ¼ 0.67). Sensitivity analysis using the new definition of hypertension ($130/80 mm Hg or requiring treatment) yielded similar results for renal outcomes, but hypertensive donors were more likely to develop CVD and diabetes.
Conclusions: Kidney donors with hypertension defined by past criteria do not appear to incur higher mortality, CVD, or ESKD. Donors with current definition of hypertension enjoyed similar renal outcomes but were more likely to develop CVD.
Level 3
We will accept donor with controlled HTN on 1-2 anti hypertension medications with annul follow up and assessment of cardiovascular system with life style modification
low salt and cessation of smoking encourage 3 to 4 time light sport per week
Reductions in renal mass and function are associated with an increase in blood pressure and the development of systemic hypertension in animal models and humans with reduced renal mass. Hypertension is widely cited as the second leading cause of ESKD in the United States, and ESKD in many former kidney donors has been attributed to hypertension.
The kidney- and cardiovascular-related concerns regarding hypertensive candidates are reflected by exclusions and also restrictions put on donor candidates with hypertension by many transplant centers.
In addition, many patients with advanced CKD who are labeled as having hypertensive nephrosclerosis not infrequently have focal segmental glomerulosclerosis and other glomerular pathologies on review of a kidney biopsy specimen.
determining outcomes of donors using the newly introduced hypertension definition (>130/80 mm Hg) would shed light on the size of the overall kidney donor pool if centers were to use it for donor eligibility.
METHODS
All donations took place between 1963 and 2007. Donors’ medical records were abstracted at each of the participating centers for baseline information, which included demographic information, anthropometric measurements, previous or current diagnosis or treatment for hypertension or hyperlipidemia, and laboratory data, as previously described.
Family history of hypertension, diabetes mellitus, kidney disease, stroke, or heart disease were also recorded. BP readings were collected on multiple occasions
during the donor evaluation, and the average of the 3 lowest readings was used as baseline to minimize misclassifying donors with white coat hypertension
Results and discussion
General Characteristics of Donors with Hypertension
Hypertensive donors (n ¼ 904) were older (48 vs. 38 years), more likely to be men, less likely to be related to the recipient, and more likely to have a college education (Table 1). Hypertensive donors had a higher weight, BMI, SBP, DBP, and a lower eGFR (83 vs. 89 ml/min/1.73 m2). Of the 251 hypertensive donors receiving antihypertensive medications, 154 received 1 agent, 44 received 2, 5 used 3 agents, and in 43 donors this information was missing. Of those treated, 50% were taking an angiotensin-converting enzyme inhibitor or angiotensin-II receptor blocker, 30% were taking diuretic medications, and the remaining received either a calcium channel blocker or a central adrenergic blocker. Hypertensive donors receiving treatment were on average 7 years older than untreated hypertensives, were more likely to be white, were less likely to be related to their recipient, and had a significantly lower SBP and DBP at donation (133 vs. 145 mm Hg for SBP and 80 vs. 84 mm Hg for DBP
Importantly, hypertensive donors receiving antihypertensive medications had a 10 ml/min/1.73 m2 lower baseline eGFR than hypertensive donors not receiving treatment (P < 0.001)
Postdonation Hypertension Development
An additional 2319 donors developed hypertension 5.1 ! 9.2 years after donation (Table 3). Donors with postdonation hypertension were younger at donation (40 vs. 48 years of age), were less likely to be related to the recipient, had a higher baseline eGFR, a lower BMI, and were less likely to have a first-degree relative with hypertension.
Outcomes of Interest at Last Follow-Up
After 17.6 ! 10.7 years from donation to last follow-up in 2010 to 2012 in donors without hypertension and 14.3 ! 10.1 years for donors with hypertension, a similar proportion were alive (4.7% vs. 6.0%, P ¼ 0.09), had CVD (12.7% vs. 13.9%, P ¼ 0.31), and had diabetes (7.1% vs. 8.2%, P ¼ 0.26
Hypertensive donors were more likely to have proteinuria (17.8% vs. 13.4%, P < 0.001) and more likely to have an eGFR < 60 and < 45 ml/min/1.73 m2.
Forty-four donors developed ESKD 19.2 !10.3 years after donation; 39 occurred in normotensive donors (0.5%) and 5 occurred in hypertensive donors (0.6%).
All 5 ESKD cases in hypertensive donors occurred in non-Hispanic whites, 2 were women, 4 were related to their recipient, 2 had a BMI > 30 kg/m2 at donation, and none developed diabetes after donation.
The composite of eGFR < 30 ml/min/1.73 m2 or
ESKD occurred in 86 donors; 72 (0.9%) in normotensive donors and 14 (1.6%) in hypertensive donors.
Postdonation serum creatinine measurements were
available in 99.7% of donors, and 70% had multiple postdonation measurements (4 ! 2.8 measurements/ donor), allowing the construction of eGFR trajectory in normotensive and hypertensive donors over time
Multivariable Risks of Mortality, CVD, and ESKD
After adjustment for baseline laboratory values, demographic factors, and the development of diabetes and hypertension after donation, we found that hypertensive donors were not more likely to die, develop cardiovascular disease, develop proteinuria, have a reduced eGFR, or have ESKD. The aHR for ESKD was 1.14 (95% CI 0.62–2.12, P ¼ 0.67
Similarly, hypertensive donors were not more likely to develop the composite of eGFR < 30 ml/min/1.73 m2 or ESKD.
Lastly, 1465 donors fulfilled the new definition of hypertension, and the analyses using the newly introduced definition of hypertension ($130/80 mm Hg) are presented in their entirety as a supplement
Conclusion
The results suggest that hypertensive
donors, compared with nonhypertensive donors, are not at increased risk for reduced eGFR, proteinuria, or ESKD. Hypertensive donors by previous definition were not more likely to die or develop CVD, either. Donors fulfilling the new definition, however, were more likely to develop CVD and diabetes. These results also show that roughly a third of kidney donors developed hypertension after donation.
level III
if blood pressure well controlled ((<140/90) by one or 2 drugs with out target organ damage we can precede the donation
Several transplant centers exclude potential kidney donors with HTN due to concerns about renal and cardiovascular complications, as HTN is a common cause of ESKD and 30% of donors develop HTN post donation compared to <10% in healthy controls.
However, HTN follows CKD in many cases and strict BP control was not associated with lower incidence of CKD but was associated with lower mortality.
HTN definition varied over years, kidney donors in the past would be considered hypertensive according to recent definitions and this allowed determining the effect of isolated HTN on long term kidney function.
This study aimed to determine long term outcomes of donors considered hypertensive at time of donation according to old HTN definition.
It included data from RELIVE study that investigated outcome of 8922 kidney donors, baseline information was abstracted from medical records, BP readings were collected on multiple occasions pre transplant and HTN was defined as BP >140/90 or the need for antihypertensive agents.
The study showed that hypertensive donors have the same risk of decreased GFR, proteinuria and ESKD as non-hypertensive donors, however donors according to new definition have higher risk of DM and CVD.
The study suggested that potential hypertensive donors can be accepted for donation as long as their BP is well controlled, no proteinuria and no end organ damage and that restriction of age to >50 years as done by several centers may be reasonable.
Younger age in hypertensive donors, African American or Hispanic may be at higher risk of ESKD and could be prohibited.
Donors considered hypertensive according to the new definition had similar renal outcomes, donors with BP>130/80 or were on antihypertensive agents were at higher risk of CVD and death, however the association with mortality and CVD was similar to that in nondonors.
Non Hispanic, white, hypertensive donors have no increased risk of ESKD compared to normotensive donors.
Hypertensive and normotensive donors had similar GFR changes and proteinuria development rate after donation.
Strengths:
Included ethnically diverse population, spanned 50 years of donation with intermediate renal outcomes in donors.
Data about serial serum creatinine, proteinuria and CVD were available.
Limitations:
Proportion of Hispanic and Asian donors were less than what is observed in the national population
Data about the cause of ESKD in donors was not available
No standardization of BP measurement.
Low statistical power which is common in studies about ESKD in kidney donors due to low event occurrence.
level 3 (retrospective study)
Hypertensive donors with well controlled BP<140/90 on one or two antihypertensive medications in absence of end organ damage are eligible for donation.
In our practice, they also should be older than 40 years.
Outcomes of Hypertensive Kidney Donors Using Current and Past Hypertension Definitions.
Hypertension is considered the second most common cause of CKD worldwide and also associated with cardiovascular diseases and is considered one of the most common contraindication for kidney donation.
The aim of the study here is to know outcomes of hypertensive kidney donors using current and past hypertension definitions.
Methods.
It is a retrospective study, used data from The Renal and Lung Living Donor Evaluation (RELIVE), evaluated outcomes of 8922 kidney donors from 3 U.S. transplant centers, in the period between 1963 and 2007. Donors’ medical records were abstracted at each of the participating centers for baseline information, which included:
=Demographic information.
=Anthropometric measurements
=Previous or current diagnosis or treatment for hypertension or hyperlipidemia.
=Laboratory data(post KTX DM, Urine proteinuria and e GFR)
=Family history of hypertension, diabetes mellitus, kidney disease, stroke, or heart disease were also recorded.
= Hypertension defined as BP>140/90 mm Hg or the requirement for antihypertensive agents.
The development of post-donation hypertension was associated with older age, male gender, BMI, and fasting plasma glucose.
Statistical Analysis: depends on definition of hypertension.
The first according to hypertension status defined by BP >=140/90 mm Hg or requirement for antihypertensive agents
Second one : according to the newer definition of >= 130/80 mm Hg or requiring treatment.
Result:
Donors with hypertension:
= Hypertensive donors were older , more likely to be men, less likely to be related to the recipient, and more likely to have a college education.
= Hypertensive donors had a higher weight, BMI, SBP, DBP, and a lower eGFR.
Post-donation Hypertension Development.
= 2319 donors developed hypertension 5.1 +/- 9.2 years after donation and characterized by younger age at donation, not related to recipient, had a higher baseline eGFR, a lower BMI, and were less likely to have a first-degree relative with hypertension.
Outcomes of Interest at Last Follow-Up.
Following up for 17.6_+ 10.1 years revealed that proteinuria and GFR< 60mil/min were more in hypertensive donors, but ESRD incidence was similar among both hypertensive and non-hypertensive donor.
Hypertensive donors had a significantly higher serum creatinine level over time, but eGFR trajectory was comparable in donors with and without hypertension.
Hypertensive donors were not more likely to die, develop cardiovascular disease, develop proteinuria, have a reduced eGFR, or have ESKD.
Donors who fulfilled the more recent definition of hypertension which is BP >130/80 mmHg had comparable renal outcomes to non-hypertensive donors but were more likely to die , were more likely to develop CVD and were more likely to develop diabetes.
Conclusion.
Hypertensive donors, compared with non-hypertensive donors, are not at increased risk for reduced eGFR, proteinuria, or ESKD.
Hypertensive donors by previous definition were not more likely to die or develop CVD but those with recent definition more likely to die, with high incidence of proteinuria ,CVD & DM.
Level of evidence: III
A retrospective cohort study.
Refer to your practice.
We are still exclude any patient with HTN but I think patient with controlled hypertension with one or two drugs with no evidence of organ damage can be accepted for donation keep in mind healthy life style, strict control of BP with long term follow up.
Introduction:
As uncontrolled chronic HTN can cause progressive renal damage, and reduced renal mass as well as decrease in renal function, Worl widely known second leading cause of ESKD, and roughly according to a recent study that post donation, 1/3 of donors may develop HTN, 15 years post KD.
Methods:
The data was collected from (RELIVE), renal and lung living donor evaluation, and (NIAID), national institute of allergy and infectious disease, that evaluate outcome of 8922 KD, from 3US transplant center.
All donations took place between 1963 and 2007.
BP records were collected based on multiple occasions during donor evaluation, an average of 3 lowest readings was taken to avoid any misclassification.
Hypertension defined as BP>/140/90 mmHg or on AHM.
Data collected about Devlopment of DM, HTN, CVD and cancer or any other condition.
Donor post donation development of DMM, staging hyperglycemia according to plasma glucose level and management required, and EOD.
Post donation HTN defined as BP>/140/90 mmHg or use of AHM.
CVD diagnosed as development of MI, CHF, stroke, or need of coronary intervention.
Proteinuria defined as; +2 in dipistick, urine proteinuria /osmolality ratio >0.42, urine random proeteinuria >15, 24hr proteinuria > 300mg/d.
CKD-EPI was used to estimate GFR.
ESKD defined as need for dialysis or listed for transplantation.
Statistical analysis:
Results:
Outcome at last follow-up:
General measures:
ESKD:
eGFR, and SCr:
Risks of mortality, CVD, and ESKD:
Donors with hypertension are not likely to die, to develop CVD, proteinuria, or have reduced eGFR, or have ESKD.
Conclusion:
level of evidence:
retrospective cohort study ((III))
Reflection of this article on my facility:
expand donor pool with hypertensive donor controlled on 2 AMH
Proper evaluation od donor perior to donation , regarding hypertension as a sole risk and the factors that may contribute to the risk,(Prpteinuria, dyslipidemia, CVD, smoking, obesity)
Thank you, Prof Halawa,
No, i will not change my practice because what we do presently is closely related to the article. In our centre, we accept patient with hypertension (BP>140/90mmHg or on not more than 2 Bp drugs) without target organ damage. For now, we are not using the new guideline of hypertension (BP>130/80mmHg) as this may greatly affect the donor pool or prolong the waiting time for the recipients. However, we do close follow up for those donors with hypertension with advice on lifestyle modification and regular home Bp monitoring.
Limitation of the study
Methods
8922 donors from 3 US centers (Minnesota- Rochester- Birmingham)
From 1963 to 2007
Old definition >= 140/90
New definition >= 130/ 80
Postdonation outcome
Death – DM- hypertension- proteinuria- eGFR less than 60 or less than 45 or less than 30
CVD – ESRD
the trend of eGFR over time was constructed using the median cubic splin plot
The difference in the change of eGFR over time between the hypertensive and non hypertensive donors was compared using liener mixed model
The hypertensive donors (904) was
older (48vs. 38)
Men> women
Higher BMI
Lower eGFR
251 hypertensive donors received antihypertensive treatment
ACEi – ARBS 50%
Diuretics 30%
CCB and others 20%
Compared observed and predicted (SBP- DBP) in donors with and without hypertension
SBP rose 2.2 vs 0.3 mmhg per decade in NON hypertensive vs hypertensive donors respectively with p value 0.001
The same for DBP (1.1 VS -1.1) p value 0.001
Development of hypertension after donation was related to younger age at donation (40 vs 48)- higher eGFR
Follow up (outcomes)
11 years non hypertensive donors
14 years hypertensive donors
Incidence of CVD – DM – eGFR less 30 or ESRD was similar in non hypertensive and hypertensive donors
Exception proteinuria incidence and eGFR less than 60 or 40 are more likely in hypertensive donors
In total ESRD was found in 44 donors 39 of them are nonhypertensive (0.5%) vs 5 are hypertensive donors (0.6%)
The ESRD occurred in those five donors in
Less than 35 years in only one case
35- 40 years in 3 cases
More than 50 years in one year
ESRD incidence rate
6.6/10000 donors years (nonhypertensive)
10.9/10000 donors years (hypertensive)
P value 0.3
Hypertensive donors have higher sCrea but eGFR was comparable
They concluded that hypertensive donors were not more likely to die or have CVD- proteinuria – decreased eGFR- ESRD than nonhypertensive donors
(Even when they compared 1465 donors divided between the old and new hypertension definition)
Limitations
The cause of ESRD is not known
There is no standardization of BP measurement
Strengths
Long duration study
Level III
Reflect on guideline
But unfortunately in our practice we still exclude any patient with hypertension
SUMMARY
Introduction
The continuous link oof hypertension as an attributable cause of chronic kidney disease in many studies have also resulted in high rejection of potential kidney donors in many parts of the world in spite of growing waiting list for kidney transplantation. Furthermore, the recent change in the definition of hypertension will definitely add to the existing problem of high rejection rate of donors with hypertension. Nevertheless, hypertension is known to worsen kidney condition if not well controlled.
Methods
Result
Conclusion
This study has shown that, kidney donors with hypertension based on old criteria were not at increased long risk of development of proteinuria, reduced GFR or ESRD. However, donors with new criteria for hypertension were observed to have long term risk of death or CVD events
The level of evidence is 3
Reflecting on the above guideline in respect of my practice. We only accept potential donor with hypertension (BP>140/90mmHg or on less than or 2 Bp medication) without target organ damage like proteinuria, LVH or grade 3 retinopathy. Moreso, those that fit into these criteria were always counseled that they must on continuous long-term clinic follow up with laboratory investigation. They are also expected to maintain appropriate weight, avoid cigarette, and low salt diet
# Please summarise this article in your own words
# Introduction:
*HTN is second leading cause of ESKD in the US. A recent analysis suggests that roughly a third of kidney donors developed HTN 15 years after donation compared with <10% in non donor healthy control subjects.
*HTN accelerates the progression of established kidney disease, but the strength of the causal link between it and incident (CKD) is not definitive, and in many cases, HTN follows the development of CKD rather than precedes it.
# The aim of this study:
To determine the impact of isolated hypertension on long-term kidney function.
# Methods:
*They used publicly available data from (RELIVE) study, (NIAID)–sponsored study that evaluated outcomes of 8922 kidney donors from 3 U.S. transplant centers: the University of Minnesota, Mayo Clinic-Rochester, and the University of Alabama-Birmingham between 1963 and 2007.
* Donors’ medical records were abstracted for baseline information, which included demographic information, anthropometric measurements, previous or current diagnosis or treatment for HTN or hyperlipidemia, and laboratory data.
* Family history of HTN, DM, CKD, stroke, or CVD were also recorded.
*BP readings were collected on multiple occasions and the average of the 3
lowest readings was used as baseline.
*Donors were asked to provide responses to quality of life surveys and were asked about developing DM, HTN, CKD, CVD, cancer, and other conditions,
* In many instances, recipients also provided information about their donors
# The results:
*The median age at donation of the entire cohort was 39 years, 56.2% were women, 85% were non-Hispanic white, 9.2% were non-Hispanic black, 1.8% were Hispanic,0.9% were Asian, and 3% were categorized as other.
*The majority (80.5%) donated to a family member; 71% had >1 first-degree relative with kidney disease and 41% with >1 first-degree relative with HTN.
*The median BMI was 25.8 kg/m2 and the median eGFR was 88 ml/min/1.73 m2.
*HTN donors had a higher weight, BMI, SBP, DBP, and a lower eGFR.
*Of the 251 hypertensive donors receiving antihypertensive medications, 154 received 1 agent, 44 received 2, 5 used 3 agents, and in 43 donors this information was missing. Of those treated.
*HTN donors receiving treatment were on average 7 years older than untreated HTN,
were more likely to be white, were less likely to be related to their recipient, and had lower SBP and DBP at donation.
*Hypertensive donors receiving antihypertensive medications had a 10 ml/min/1.73 m2 lower baseline eGFR than hypertensive donors not receiving treatment.
* 2319 donors developed hypertension 5.1- 9.2 years after donation.
*Donors with post donation hypertension were younger at donation and were less likely to be related to the recipient, had a higher baseline eGFR, a lower BMI, and were less likely to have a first-degree relative with HTN.
*The development of postdonation hypertension
was associated with older age, male gender, BMI, and fasting plasma glucose.
*Outcomes of interest at last follow-up in donors without HTN and for donors with HTN, a similar proportion were alive, had CVD (12.7% vs. 13.9%), and had DM (7.1% vs. 8.2%). *HTN donors were more likely to have proteinuria (17.8% vs. 13.4%) and more likely to have an eGFR < 60 and < 45 ml/min/1.73 m2. However, the occurrence of eGFR < 30 ml/min/1.73 m2 or ESKD was similar in donors with and without HTN.
# Conclusions:
Kidney donors with hypertension defined by past criteria do not appear to incur higher mortality, CVD, or ESKD. Donors with current definition of hypertension enjoyed similar renal outcomes but were more likely to develop CVD.
# What is the level of evidence provided by this article?
*It is a retrospective study level 3.
# Please reflect on the guidelines and refer to your practice.
* HTN defined by office BP >=140/90 mmHg (confirmed by ABPM), exception can be made only when there is no other suitable donors, so we can choose those with mild HTN well controlled with one or two drugs and with no end organ damage, and the age of the donor is > 50 years old, eGFR > 80 ml/min and 24 hours urine albumin <30 mg/day.
Please summarise this article in your own words
The kidney and cardiovascular related concerns regarding hypertensive candidates are reflected by exclusions
and also restrictions put on donor candidates with hypertension by many transplant centers.
The definition of hypertension has evolved over the years, and therefore many kidney donors who donated in the past, particularly early on in transplantation history, would be considered hypertensive by today’s standards.
Aim of the study:
Determining outcomes of donors with HTN using the old and new HTN definition.
Methods
Used data from RELIVE study (1963- 2007), 8922 kidney donors from 3 transplant centers
Two analyses were conducted, first according to the old definition of HTN (140/90 or more) or requirement for antihypertensive medications and the second according to the newer definition (130/80 or more) or requiring treatment (here, normal 130/80 or less)
904 hypertensive donors versus 7817 donors with no HTN
Study result and outcome
1. Hypertensive donors were more likely to have proteinuria (17.8% vs. 13.4%) and more likely to have an eGFR < 60 and < 45 ml/min/1.73 m2.
2. The occurrence of eGFR < 30 ml/min/1.73 m2 or ESKD was similar in donors with and without hypertension.
3. The development of ESKD in hypertensive donors was associated with BMI at donation and having a first- degree relative with hypertension.
4. Hypertensive donors had a significantly higher serum creatinine level over time, but eGFR trajectory was comparable in donors with and without hypertension.
5. Hypertensive donors were not more likely to die, develop cardiovascular disease, develop proteinuria, have a reduced eGFR, or have ESKD.
6. Conclusion: Hypertensive donors, compared with non-hypertensive donors, are not at increased risk for reduced eGFR, proteinuria, or ESKD.
Level of evidence:
– Level 3, observational retrospective study
In our practice,
– donor with bl.p.<140/90 can be considered for donation
– if well controlled HTN(<140/90) on one or 2 drugs in absence of EOD or CVS risk factors also can be considered for donation
– in all , counselling regarding the risk post donation & importance of healthy life style after donation is obtained.
Thank you
– HTN is one of the most common causes of CKD. in most of cases the incidence of HTN precedes the CKD but the strength of casual relation is not definitive. pre donation hypertension can increase risk of CKD, also risk of HTN increases after donation in comparison to non-donor healthy population. SPRINT trial showed decrease lower mortality with strict bl.p. control but it didn’t show lower incidence of CKD . this study comparing the outcomes of the old donors who were at the time of donation not diagnosed as HTN by definition at that time but with the newly introduced definition of HTN >130/80, they are considered HTN .
Methods:
– ascertained mortality, CVD, proteinuria, estimated glomerular filtration rate (eGFR) trajectory, reduced eGFR, and end-stage kidney disease (ESKD) in 904 hypertensive donors (blood pressure [BP] >140/90 mm Hg or receiving treatment) versus 7817 donors with BP <140/90 mm Hg.
Results:
– Hypertensive donors were older, 58.1% were <50 years of age, and they had a lower eGFR. The
majority were white and related to their recipient.
– At the end of follow-up, 14.3 +- 10.1 years (range 4–48
years) from donation, hypertensive and nonhypertensive donors had a similar prevalence of cardiovascular
disease and renal outcomes. The multivariable risk of mortality, CVD, and proteinuria were also comparable
in normotensive and hypertensive donors.
– eGFR slope over time was similar in hypertensive and nonhypertensive donors, and in total 5 hypertensive and 39 normotensive donors developed ESKD 19.2 +- 10.3
years after donation.
– Sensitivity analysis using the new definition of hypertension (>130/80 mm Hg or requiring treatment) yielded similar
results for renal outcomes, but hypertensive donors were more likely to develop CVD and diabetes.
Conclusions:
– Kidney donors with hypertension defined by past criteria do not appear to incur higher mortality, CVD, or ESKD. Donors with current definition of hypertension enjoyed similar renal outcomes but were more likely to develop CVD
Level of evidence:
– Level 3, observational retrospective study
In our practice,
– donor with bl.p.<140/90 can be considered for donation
– if well controlled HTN(<140/90) on one or 2 drugs in absence of EOD or CVS risk factors also can be considered for donation
– in all , counselling regarding the risk post donation & importance of healthy life style after donation is obtained
Thank you
Arecont analysis suggest third of kidney donors develop HTN 15 years after donation with <10% in non donor healthy control subject.
The new HTN definition >or equal 130/80 mmHg will affect the size of kidney donor pool if centre were to use it for donor eliglibility.
Methods
NIAID-sponsored study that evaluated outcomes of 8922 kidney donors from 34.5 transplant centres from 1963 to 2007.
Collect average 3 lowest readying collect on multiple occasions.
HTN defined as > or more 140/90 mmHg or requirement of anti HTN agents.
Post donation DM fasting plasma glucose > or more 140/90 mmHg.
Proteinuria defined by 24 hour protein >300 mg /day.
Result:
RELIVE study donors 8922 kidney donors,8721 donated a kidney between 1963 and 2007,CVS in 98%,eGFR in 97.1% personation HTN in 98%,postdonation DM in 90.2% and proteinuria data in 89.9%
Post donation HTN development:
2319 donors develop HTN 5.1_ or +9.2 years after donation .
After 17.6 -or +10.7 years from donation in donors with or without HTN a similar proportion were alive and had DM.
HTN donors were more likely have proteinuria and eGFR <69 ,however eGFR <30 and ESRD was similar in donor without HTN.
CVD outcome in donors ,no difference between non-hypertensive and HTN ,by old HTN definition.
HTN donors with new definition more likely to develop CVD and DM.
Kidney donors develop HTN after donation ,although ESRD is a rare after donation and most of the study lack of statical power to make conclusion.
Strength of this study:
The population studied span 50 years of kidney donation.
Donor had intermediate renal outcome such as reduced e GFR ,creatinine ,proteinuria and CVD which are not captured in national donor data base.
Limitation of this study:
The population of non -Hispanic white donors in the RELIVE study was significant higher than in the US donor pool(70%).
Proportion of Hispanic and Asian donors were less than what is observed.
The RELIVE study does not have cause of ESRD in donor,
There was no standardized of how BP measure at 3 occasion.
Non Hispanic white HTN donors do not have an increased risk of ESRD compared with normotensive kidney donors.
eGFR change after donation and development were similar between HTN and normotensive donors.
level3
in our centre donor with HTN controlled with one or 2 Anti HTN medication with no organ damage ,can be acceptable donor for kidney transplantation.
Thank you, will you change your practice based on this paper?
Outcomes of Hypertensive Kidney Donors Using Current and Past Hypertension Dentitions
Summary of the Article
This is a retrospective study, used data from The Renal and Lung Living Donor Evaluation (RELIVE), evaluated outcomes of 8922 kidney donors from 3 U.S. transplant centers, in the period between 1963 and 2007.
The development of postdonation hypertension was associated with older age, male gender, BMI, and fasting plasma glucose.
Study result and outcome
1. Hypertensive donors were more likely to have proteinuria (17.8% vs. 13.4%) and more likely to have an eGFR < 60 and < 45 ml/min/1.73 m2.
2. The occurrence of eGFR < 30 ml/min/1.73 m2 or ESKD was similar in donors with and without hypertension.
3. The development of ESKD in hypertensive donors was associated with BMI at donation and having a first- degree relative with hypertension.
4. Hypertensive donors had a significantly higher serum creatinine level over time, but eGFR trajectory was comparable in donors with and without hypertension.
5. Hypertensive donors were not more likely to die, develop cardiovascular disease, develop proteinuria, have a reduced eGFR, or have ESKD.
6. Conclusion: Hypertensive donors, compared with non-hypertensive donors, are not at increased risk for reduced eGFR, proteinuria, or ESKD.
Strengths of the study
a) The study population is ethnically diverse.
b) Longer duration of study period( spans 50 years of kidney donation).
c) Donors had ascertainable intermediate renal outcomes.
Limitations of the study
a) The proportion of non-Hispanic white donors in the RELIVE study was significantly higher.
b) The proportion of Hispanic and Asian donors were less than what is observed nationally.
c) No standardization of how BP measurements were carried out at the 3 centers.
What is the level of evidence provided by this article?
This is a retrospective cohort study
Level of evidence grade 3.
Please reflect on the guidelines and refer to your practice.
In our practice, we don’t attempt to proceed with hypertensive donors in the transplant process.
Thank you, well you change your practice based on this paper?
– Please summarise this article in your own words
The kidney and cardiovascular related concerns regarding hypertensive candidates are reflected by exclusions
and also restrictions put on donor candidates with hypertension by many transplant centers.
The definition of hypertension has evolved over the years, and therefore many kidney donors who donated in the past, particularly early on in transplantation history, would be considered hypertensive by today’s standards.
Aim of the study:
Determining outcomes of donors with HTN using the old and new HTN definition.
Methods:
The study populations: participants kidney donors from RELIVE study from 3 US transplant centers, who donated between 1963 and 2007.
Hypertensive donor compared with normotensive donor for the composite outcomes.
The participating study sites contacted donors between 2010 and 2012 for follow-up and outcomes, which defined as:
CVD: any of the following: MI , CHF, TIA, stroke, or need for coronary or peripheral arterial intervention (angioplasty, stenting or bypass).
ESKD: (eGFR calculated by CKD-EPI) need for dialysis, or receiving or being listed for a kidney transplant.
HTN: as use of antihypertensive medications, SBP>=140mmHg or a DBP>=90mmHg.
Proteinuria: as one or more of the following: urine protein by dipstick 2., urine protein/osmolality
>0.42 ratio, urine random protein >15mg/dL or 24-h protein >300mg/day.
Exclusion: any donors with proteinuria, measured GFR or creatinine clearance <80mL/min
We ascertained mortality, CVD, proteinuria, estimated glomerular !ltration rate (eGFR) trajectory, reduced eGFR, and end-stage kidney disease (ESKD) in 904 hypertensive donors (blood pressure [BP] $140/90 mm Hg or receiving treatment) versus 7817 donors with BP <140/90 mm Hg.
Statistical Analysis: Two analyses were conducted;
First according to hypertension status defined by BP >=140/90 mm Hg or requirement for antihypertensive agents Second according to the newer definition of >= 130/80 mm Hg or requiring treatment.
Results:
Hypertensive donors were older, more likely to be men, less likely to be related to the recipient, and more likely to had a higher weight, BMI, SBP, DBP, and a lower eGFR.
The mean follow up period 14.3-+10.1 years from donation for hypertensive donors.
Hypertensive and non-hypertensive donors had a similar prevalence of cardiovascular disease and renal outcomes.
The multivariable risk of mortality, CVD, and proteinuria were also comparable in normotensive and hypertensive donors.
Total 5 hypertensive and 39 normotensive donors developed ESKD 19.2 -+ 10.3 years after donation aHR1.14
The development of ESKD in hypertensive donors was associated with BMI at donation and having a first degree
relative with hypertension. No cases of ESKD occurred in hypertensive donors in the first 10 years, and the incidence after 30 years was 51.8.
eGFR slope over time was similar in hypertensive and non-hypertensive donors.
Sensitivity analysis using the new definition of hypertension yielded similar results for renal outcomes, but hypertensive donors were more likely to develop CVD and diabetes.
Conclusions: Kidney donors with hypertension defined by past criteria do not appear to incur higher mortality, CVD, or ESKD. Donors with current definition of hypertension had similar renal outcomes but were more likely to develop CVD.
Strength:
– Long follow up period, spans 50 years of kidney donation.
– Ethnically diverse.
– Donors had ascertainable intermediate renal outcomes.
Limitations:
– The proportion of non-Hispanic white donors in the RELIVE study was significantly higher than observed in US donor pool.
– Dataset does not have the cause of ESKD in donors.
– The outcome of kidneys from hypertensive donors fared in the recipients, is not known.
– No standardization of how BP measurements were carried out.
– What is the level of evidence provided by this article?
Level 3, retrospective cohort study.
– Please reflect on the guidelines and refer to your practice.
Donors with controlled BP and no end organ damage are allowed to donate.
Despite the imitations, donor with old definition of HTN can be reassured and counseled about the future risks.
Strict follow up and lifestyle measures to reduce the risk as the BMI clearly play a role.
Thank you, and on a maximum of 2 anti-hypertensive agents.
Introduction
A third of kidney donors developed hypertension 15 years after kidney donation compared with less than 10% in non-donor healthy control subjects. Pre-donation HTN in donors > 50 years of age was associated with an overall incidence of ESKD of < 1%.
HTN accelerates the progression of established CKD but the strength of the causal link between HTN and incident CKD is not definitive.
Strict BP control in the SPRINT trial, while hugely associated with a lower mortality did not appear to lower CKD incidence.
The definition of HTN has also evolved over the years, and therefore many kidney donors who donated in the past would be considered hypertensive by todays standards. These would be a cohort of healthy individuals with no proteinuria, CVD or renal dysfunction and can be studied to look at outcomes post-donation
Methodology
This was a retrospective case control study. It utilized the database of the RELIVE study which had 8922 kidney donors from three U.S centers. All donations took place between 1963 – 2007. Donor medical records were obtained from each of the three study sites for the baseline information, anthropometrics, previous/current Dx of HTN or treatment for HTN or dyslipidemia. Family history of HTN, DM, CKD, stroke or heart disease was also recorded.
BP recordings were collected on multiple occasions during the donor evaluation and the average of the three lowest readings were used as baseline. HTN was defined as a BP of more than or equal to 140/90 mmHg or the requirement of antihypertensive agents.
Between 2010 and 2012, the three centers contacted the donors requesting participation in the RELIVE study. Donors were asked to provide responses to quality of life surveys and the development of:
2 analysis were conducted:
First, according to hypertension status defined by BP > 140/90 mmHg or requirement of antihypertensive agents
Second, According to the newer definition of HTN as BP > 130/80 mmHg or requiring treatment
The post-donation outcomes looked at included:
Results
From the 8922 kidney donors, 8721 were included in the study. 7817 had normal BPs and 904 had BPs > 140/90 mmHg. Median age was 39 years. 56.2% were women, 85% were non-Hispanic whites, 9.2% were non-Hispanic Blacks, 1.8% were Hispanics, 0.9% were Hispanics and 3% were categorized as other.
The majority of the donors donated to a family member
Hypertensive donors were older (48 vs 38 years), more likely to be males, less likely to be related to the recipient and more likely to have a college education
Majority of the donors on antihypertensive medication were on one antihypertensive and majority were on RAAS blockers.
An additional 2319 donors developed HTN after an average of 5.1 years after donation.
After an average of 17.6 years of follow up for non-hypertensive donors and 14.3 for hypertensive donors, there was no difference in mortality, development of CVD, DM and the composite of ESKD or eGFR < 30 mls/min/1.73m2.
Hypertensive donors were more likely to have proteinuria and more likely to have an eGFR of < 60 and < 45 mls/min/1,73m2.
After adjustment for baseline laboratory values, demographic factors and the development of DM and HTN, hypertensive donors compared with non-hypertensive donors had similar rates of mortality, developing proteinuria, low GFR, ESKD or the composite of ESKD or eGFR < 30 mls/min/1.73m2
Using the new definition of HTN (BP > 130/80 mmHg), hypertensive donors had comparable renal outcomes non-hypertensive donors but had a higher rate of mortality (not statistically significant), developing CVD and developing DM
Conclusion
Hypertensive donors compared to non-hypertensive donors are not at an increased risk for reduced GFR, proteinuria, ESKD, mortality or CVD
Using the new definition of HTN, hypertensive donors are more likely to develop CVD and DM
Based on the data from this study, potential hypertensive donors may be considered for donation as long as the BP is well controlled, they have no proteinuria and no end organ damage
Limitations:
The level of evidence is level 3 as this is a case control study
In my practice we do allow donors with HTN who are controlled with one or two antihypertensive medications
Thank you, and a maximum 2 agents
Outcomes of Hypertensive Kidney Donors Using Current and Past Hypertension Definitions
♧Introduction:
▪︎Hypertension is widely cited as the second leading cause of ESKD in the US, and ESKD in many former kidney donors has been attributed to hypertension.
▪︎ A recent analysis suggests that roughly a third of kidney donors developed hypertension 15 years after donation compared with <10% in nondonor healthy control subjects, and in a separate analysis from the same investigators, predonation hypertension in donors >50 years of age was ass with an overall ESKD incidence of <1%.
▪︎HTN accelerates the progression of established kidney disease, but the strength of the causal link between HTN and incident CKD is not definitive.
▪︎The definition of HTN has evolved over the years, and therefore many kidney donors who donated in the past would be considered HTN by today’s standards.
♧The aim of the study:
1. To provide a unique opportunity to study the impact of isolated HTN on long-term kidney function because donors have no evidence of any renal involvement, and no major comorbidities at donation. This also may inform the current selection criteria pertaining to donor candidates with HTN.
2. To determine outcomes of donors using the newly introduced hypertension definition ($130/80 mm Hg) to shed light on the size of the overall kidney donor pool if centers were to use it for donor eligibility.
♧ Methods:
▪︎Mortality, CVD, proteinuria, eGFR trajectory, reduced eGFR, ESKD in 904 hypertensive donors (BP $140/90 mm Hg or receiving treatment) versus 7817 donors with BP <140/90 mm Hg were ascertained.
♧ Results:
▪︎Hypertensive donors were older, 58.1% were <50 years of age, and they had a lower eGFR.
▪︎The majority were white and related to their recipient. At the end of follow-up, 14.3 + 10.1 years (range 4–48 years) from donation, hypertensive and non-hypertensive donors had a similar prevalence of CVDand renal outcomes. ▪︎The multivariable risk of mortality, CVD& proteinuria were also comparable in normotensive & hypertensive donors.
▪︎eGFR slope over time was similar in hypertensive and non-hypertensive donors, and in total 5 hypertensive and 39 normotensive donors developed ESKD 19.2 + 10.3 years after donation. ▪︎Sensitivity analysis using the new definition of hypertension ($130/80 mm Hg or requiring treatment) yielded similar results for renal outcomes, but hypertensive donors were more likely to develop CVD and diabetes.
♧Conclusions:
▪︎The results suggest that hypertensive donors, compared with non-hypertensive donors, are not at increased risk for reduced eGFR, proteinuria, orESKD.
▪︎ Hypertensive donors by previous definition were not more likely to die or develop CVD.
▪︎Donors fulfilling the new definition, however, were more likely to develop CVD and diabetes.
▪︎These results also show that roughly a third of kidney donors developed HTN after donation.
▪︎Donors with current definition of hypertension enjoyed similar renal outcomes but were more likely to develop CVD.
▪︎Based on the provided data of this study, they proposed that hypertensive donors can perhaps be considered for donation more liberally as long as their BP is well controlled (as confirmed by ambulatory BP monitoring), they have no proteinuria and they have no end organ damage (no left ventricular hypertrophy or hypertensive retinopathy). ▪︎Restricting the acceptance of hypertensive donors to those above a certain age (usually 50 years of age) is common.
Younger age in a hypertensive donor of AA or Hispanic ethnicity may carry a risk for ESKD.
▪︎While analyses using the new definition of HTN yielded similar results for renal outcomes, donors with BP $ 130/80 mm Hg or who were receiving treatments were more likely to die and have CVD.
♧ Strengths of the study:
1. The population studied spans 50 years of kidney donation, is ethnically
diverse.
2. Donors had ascertainable intermediate renal outcomes, such as reduced GFR, serial serum creatinine availability, proteinuria assessment, and CVD, which are not captured in national donor databases.
♧ Limitations:
1. The proportion of non-Hispanic white donors in the RELIVE study was significantly higher than what is observed in the larger U.S. donor pool
2, The proportion of Hispanic and Asian donors were less than what is
observed nationally.
3. The RELIVE study public dataset does not have the cause of ESKD in donors
4. There was no standardization of how BP measurements were carried out at the 3 centers
5. ESKD was not ascertained by linkage to the Organ Procurement and Transplantation Network or the U.S. Renal Data System.
☆What is the level of evidence provided by this article? Level III
☆Please reflect on the guidelines and refer to your practice.
In our center we can accept the hypertensive kidney donor as Extended Donor Criteria only if the blood pressure is well controlled (with not more than one antihypertensive drug) and with no evidence of end organ damage
Thank you
Methods:
data collected from the participants in the RELIVE study.
BP readings were collected on multiple occasions during the donor evaluation, and the average of the 3 lowest readings was used as a baseline to minimize misclassifying donors with white coat hypertension.
Hypertension was defined by the extant definition at the time of the study, which was BP >140/90 mm Hg or the requirement for antihypertensive agents.
Between 2010 and 2012, the 3 RELIVE study centers contacted donors by mail requesting participation in the RELIVE study.
Donors were asked to respond to quality-of-life surveys and were asked about developing diabetes, hypertension, kidney disease, CVD, cancer, and other conditions. In addition, participating centers provided all follow-up data they had on their donors.
mortality, CVD, proteinuria, eGFR trajectory, reduced eGFR, and ESKD in 904 hypertensive donors (BP >140/90 mm Hg or receiving treatment) versus 7817 donors with BP <140/90 mm Hg.
Results:
Hypertensive donors were older and had a lower eGFR.
The majority were white and related to their recipient.
At the end of follow-up (range 4–48 years) from donation, hypertensive and nonhypertensive donors had a similar prevalence of cardiovascular disease and renal outcomes.
The multivariable risk of mortality, CVD, and proteinuria was also comparable in normotensive and hypertensive donors.
eGFR slope over time was similar in hypertensive and nonhypertensive donors, and in total, 5 hypertensive and 39 normotensive donors developed ESKD 19.2 +-10.3 years after donation. Sensitivity analysis using the new definition of hypertension( > or equal to 130/80 mm Hg or requiring treatment) yielded similar results for renal outcomes. Still, hypertensive donors were more likely to develop CVD and diabetes.
Conclusion:
Kidney donors with hypertension defined by past criteria do not appear to incur higher mortality, CVD, or ESKD.
Donors with the current definition of hypertension enjoyed similar renal outcomes but were more likely to develop CVD.
Level 3 (retrospective cohort study).
Guidelines accept donations from hypertensive people with a well-controlled BP using a single or 2 antihypertensive medications in the absence of end-organ damage.
In my practice, we follow these guidelines for living donations.
Thank you
V. Outcomes of Hypertensive Kidney Donors Using Current and Past Hypertension Dentitions
Please summarise this article in your own words
Introduction
HTN is the 2ndleading cause of ESRD in the US, & ESRD in many former kidney donors is due to HTN.
A 3rd of kidney donors developed HTN 15 years after donation compared with <10% in non-donor healthy controls.
Pre-donation HTN in donors >50 years of age was associated with an overall ESRD of <1%.
Many centers do not accept kidney donor candidates with HTN due to concerns of kidney disease & CVD.
It is well known that HTN accelerates the progression of kidney disease; however, the strength of the causal link between HTN & incident CKD is not definitive. HTN follows the development of CKD in many cases.
In = the SPRINT study, strict BP control while hugely lowered mortality, did not lower CKD incidence.
The definition of HTN has changed over the years; many donors who donated in the past would be considered hypertensive by today’s standards.
Outcomes of donors using the newly introduced HTN definition (=/>130/80) would show the size of the overall kidney donor pool if centers were to use it for donor acceptance.
Methods
This study used the publicly available data from the RELIVE study (evaluated outcomes of 8922 kidney donors from 3 U.S transplant centers between 1963 & 2007.
Donors’ baseline information included demographic data, anthropometric measurements, previous or current diagnosis or treatment for HTN or hyper-lipidemia, laboratory data, FH of HTN, DM, kidney disease, stroke, or heart disease.
HTN was defined by the existent definition at the time of the study (=/>140/90 mm Hg or the requirement for medication).
Post-donation DM was present if self-reported by the donor, FBG=/>126 mg/dl, the requirement for insulin, oral hypo-glycemic agents, or evidence of end organ
damage (retinopathy or nephropathy). Post-donation HTN was defined as use of medications or a home, center, or office-based BP =/>140/90 mm Hg.
CVD was defined as a diagnosis of MI, CHF, stroke, or the need for coronary or peripheral arterial interventions. Proteinuria was defined as any of:
-Urine dipstick protein =/>2
-Urine protein/ osmolality ratio >0.42
-Urine random protein >15 mg/dl
-24-hour protein >300 mg/day.
The CKD-EPI used to calculate the eGFR. ESRD was defined by the need for dialysis or being listed for or receiving a TX.
Statisticas
Two analyses were done:
The 1staccording to HTN status defined by BP =/>140/90 mm Hg or requirement for medications
The 2ndaccording to the newer definition of normo-tension as BP <130/80 mm Hg versus =/>130/80 mm Hg or requiring treatment.
All analyses done by Stata software version 16.1. P < 0.05 was considered significant.
Results
·Median age at donation: 39 years.
·56.2% were women
·85% were non-Hispanic white, 9.2% were non-Hispanic black, 1.8% were Hispanic, 0.9% were Asian, & 3% categorized as other.
·80.5% donated to a family member
·71% had a 1stdegree relative with kidney disease
·41% with 1stdegree relative with HTN.
·Median BMI: 25.8 kg/m2
·Median Egfr: 88 ml/min.
·6352 (72.8%) had SBP <130 mm Hg, 1465 (16.8%) SBP < 140 mm Hg, 653 (7.5%) SBP =/>140 mm Hg, & 251 (2.9%) were receiving medications.
General characteristics of donors with HTN
Hypertensive donors (n=904) were:
·Older (48 vs. 38 years)
·More likely to be men
·Less likely to be related to the recipient
·More likely to have a college education
·With a higher weight, BMI, SBP, DBP, & a lower eGFR (83 vs. 89 ml/min).
Of the 251 hypertensive donors receiving medications, 154 received 1 agent, 44 received 2, 5 used 3 agents, & in 43 donors this information was missing.
Of those treated, 50% were taking an ACI/ ARB, 30% were taking diuretic, & the remaining received either a CCB or a central adrenergic blocker.
Hypertensive donors on treatment were older than untreated ones, more likely to be white, less likely to be related to the recipient, and had a lower SBP and DBP at donation.
SBP rose by 2.2 mm Hg/decade in non-hypertensive donors versus -0.3 mm Hg / decade in hypertensive donors.
DBP rose by 1.1 mm Hg/ decade in non-hypertensive donors versus -1.1mm Hg/ decade in hypertensive donors (P < 0.001).
Postdonation HTN Development
An additional 2319 donors developed HTN 5.1-9.2 years after donation.
Donors with postdonation HTH were younger at donation (40 vs. 48), less likely to be related to the recipient, had a higher baseline eGFR, a lower BMI, less likely to have a 1stdegree relative with HTN.
Post-donation HTN was associated with older age, male gender, BMI, & FBG; P < 0.05 for all.
Outcomes of Interest at Last Follow-Up
Similar proportion of donors without or with HTN were alive (4.7% vs. 6.0%), had CVD (12.7% vs. 13.9%), & had DM (7.1% vs. 8.2%).
Hypertensive donors were more likely to have proteinuria (17.8% vs. 13.4%, P < 0.001) & more likely to have eGFR < 60 &< 45 ml/min.
The occurrence of eGFR < 30 ml/min or ESRD was similar in donors with & without HTN.
44 donors developed ESRD 19.2+/-10.3 years after donation; 39 occurred in normo-tensive donors (0.5%) and 5 occurred in hypertensive donors (0.6%).
The overall ESRD incidence rate similar in hypertensive & non-hypertensive donors.
Multivariable risks of mortality, CVD, & ESRD
·Hypertensive donors were not more likely to die, develop CVD, develop proteinuria, have a reduced eGFR, or have ESRD.
·Hypertensive donors were not more likely to develop the composite of eGFR < 30 ml/min/1.73 m2 or ESRD.
·Competing risk analysis found no statistically significant differences in the cumulative incidence for any of the outcomes studied between non-hypertensive & hypertensive outcomes.
·1465 donors fulfilled the new definition of HTN (=/>130/80).
·Donors who fulfilled the more recent definition of HTN had comparable renal outcomes to non-hypertensive donors
but were more likely to die, were more likely to develop CVD, & were more likely to develop diabetes.
Conclusion:
Hypertensive donors, compared with non-hypertensive donors, are not at increased risk for reduced eGFR, proteinuria, or ESRD. Hypertensive donors by previous definition
were not more likely to die or develop CVD.
Donors fulfilling the new definition, however, were more likely to develop CVD & diabetes.
A third of kidney donors developed HTN after donation.
=========================
What is the level of evidence provided by this article?
Level III
=========================
Please reflect on the guidelines and refer to your practice.
In our transplant center we accept hypertensive patients as ECD given that the BP is well controlled and there is no evidence of end organ damage.
Thank you, we do the same in the UK. A maximum of 2 agents with no end-organ damage.
The definition of hypertension has evolved over the years, and therefore many kidney donors who donated in the past, particularly early on in transplantation history, would be considered hypertensive by today’s standards. Many patients who donated many years before with a systolic blood pressure of 140 were considered normotensive, while recent guidelines categorize them in hypertension group.
Determining outcomes of donors using the newly introduced hypertension definition (130/80 mm Hg) would shed light on the size of the overall kidney donor pool if centers were to use it for donor eligibility.
In this study, authors used available data from The Renal and Lung Living Donor Evaluation (RELIVE) study, a National Institute of Allergy and Infectious Diseases (NIAID)–sponsored study that evaluated outcomes of 8922 kidney donors from 3 U.S. transplant centers.
General Characteristics of Donors with Hypertension
– Hypertensive donors were older, more likely to be men, less likely to be related to the recipient, and more likely to have a college education.
– Hypertensive donors had a higher weight, BMI, SBP, DBP, and a lower eGFR
– Hypertensive donors receiving treatment were on average 7 years older than untreated hypertensives, were more likely to be white, were less likely to be related to their recipient, and had a significantly lower SBP and DBP at donation.
Post-donation Hypertension Development
After donation, 2319 donors developed hypertension. Donors with post-donation hypertension:
– were younger at donation
– less likely to be related to the recipient
– had a higher baseline eGFR
– had a lower BMI
– less likely to have a first-degree relative with hypertension
Outcomes of Interest at Last Follow-Up
– After long term follow-up after donation, donors without hypertension and donors with hypertension, have similar proportion of being alive, similar incidence of CVD and diabetes.
– Hypertensive donors were more likely to have proteinuria (17.8% vs. 13.4%, P < 0.001) and more likely to have an eGFR < 60 and < 45 ml/min/1.73 m2.
– The occurrence of eGFR < 30 ml/min/1.73 m2 or ESKD was similar in donors with and without hypertension.
Multivariable Risks of Mortality, CVD, and ESKD
After adjustment for baseline laboratory values, demographic factors, and the development of diabetes and hypertension after donation, we found that hypertensive donors were not more likely to die, develop cardiovascular disease, develop proteinuria, have a reduced eGFR, or have ESKD.
This is a retrospective cohort study level of evidence III
Thank you
Introduction:
Ø As many as 50% of U.S. transplant centers do not accept kidney donor candidates with hypertension, citing the link between hypertension, kidney disease, and cardiovascular disease (CVD).
Ø Hypertension is widely cited as the second leading cause of ESKD in the United States, and ESKD in many former kidney donors has been attributed to hypertension.
Ø Hypertension accelerates the progression of established kidney disease. Still, the strength of the causal link between hypertension and incident chronic kidney disease (CKD) is few definitive patients with advanced CKD. They have hypertensive nephrosclerosis and not infrequently have focal segmental glomerulosclerosis and other glomerular pathologies on review of a kidney biopsy specimen.
Methods:
Ø Available data from The Renal and Lung Living Donor Evaluation (RELIVE) study, a National Institute of Allergy and Infectious Diseases (NIAID)–a sponsored study that evaluated outcomes of 8922 kidney donors from 3 U.S. transplant centers: the University of Minnesota, Mayo Clinic-Rochester, and the University of Alabama-Birmingham. All donations took place between 1963 and 2007
Ø Donors’ medical records were abstracted at each participating center for baseline information, including demographic information, anthropometric measurements, previous or current diagnosis or treatment for hypertension or hyperlipidemia, and laboratory data.
Ø also recorded Family history of hypertension, diabetes mellitus, kidney disease, stroke, or heart disease
Ø The 3 RELIVE study centers contacted donors by mail requesting participation in the RELIVE study.
Ø Post donation hypertension was defined as the use of antihypertensive medications specifically used for hypertension treatment or a documented home, center, or office-based B.P.>140/90 mm Hg.
Statistical Analysis
All analyses were performed using Stata software (version 16.1; Stata Corp LLC, College Station, TX, USA). P < 0.05 was considered statistically significant.
Results:
General Characteristics of RELIVE Study Donors
Ø Of 8922 kidney donors, 8721 donated a kidney between 1963 and 2007, had multiple pre-donation B.P. measurements available and had their vital statuses ascertained. The critical rate was ascertainable in 99.8% of the donors, CVD in 98%, eGFR value in 97.1%, post-donation hypertension in 98%, post-donation diabetes in 90.2%, and proteinuria data in 89.9%.
Ø The median age at a donation of the entire cohort was 39 years
Ø The majority (80.5%) donated to a family member; 71%
Ø The median BMI was 25.8 kg/m2, and the median eGFR was 88 ml/min/1.73 m2
Ø In total, 6352(72.8%) had SBP <130 mm Hg, 1465 (16.8%) had 130< SBP < 140 mm Hg, 653 (7.5%) had SBP >140 mm Hg, and 251 (2.9%) were receiving antihypertensive medications.
General Characteristics of Donors with Hypertension:
Ø Hypertensive donors (n = 904) were older (48 vs. 38 years),
Ø Post donation Hypertension Development 2319 donors developed hypertension 5.1± 9.2 years after donation.
Outcomes of Interest at Last Follow-Up
Ø After 17.6 ± 10.7 years from donation to last follow-up in 2010 to 2012 in donors without hypertension and 14.3 ± 10.1 years for donors with hypertension, a similar proportion were alive (4.7% vs. 6.0%, P =0.09), had CVD (12.7% vs. 13.9%, P = 0.31), and had diabetes (7.1% vs. 8.2%, P = 0.26.
Ø Forty-four donors developed ESKD 19.2 ±10.3 years after donation; 39 occurred in regular tensive donors.
Ø The composite of eGFR < 30 ml/min/1.73 m2 or ESKD occurred in 86 donors; 72 (0.9%) in normotensive donors and 14 (1.6%) in hypertensive donors.
Multivariable Risks of Mortality, CVD, and ESKD:
Ø After adjustment for baseline laboratory values, demographic factors, and the development of diabetes and hypertension after donation, we found that hypertensive donors were not more likely to die, develop cardiovascular disease, develop proteinuria, have a reduced eGFR, or have ESKD. The aHR for ESKD was 1.14 (95% CI 0.62–2.12, P = 0.67
Conclusions:
Ø Kidney donors with hypertension defined by past criteria do not appear to include higher mortality, CVD, or ESKD. Donors with the current definition of hypertension enjoyed similar renal outcomes but were more likely to develop CVD
Limitation :
1-The RELIVE public study dataset does not have the cause of ESKD in donors, and it would also have been ideal to know how kidneys from hypertensive donors fared in the recipients
Level 3 retrospective cohort study
in practice we donot accept hypertensive donor
Thank you
Will you change your practice based on this article?
Please summarise this article in your own words
Introduction
HTN is the second most common cause of ESRD. Most transplant centers do not accept donors with HTN as there is clear relation with CVD and kidney disease. In a recent study one-third of donors developed HTN 15 years after donation compared with <10% in healthy matched nondonors
Aim of the study: Address the outcomes of HTN in kidney donors (the old and new definition) on mortality, CVD, proteinuria, eGFR, and ESKD
Methods
Used data from RELIVE study (1963- 2007), 8922 kidney donors from 3 transplant centers
Two analyses were conducted, first according to the old definition of HTN (140/90 or more) or requirement for antihypertensive medications and the second according to the newer definition (130/80 or more) or requiring treatment (here, normal 130/80 or less)
904 hypertensive donors versus 7817 donors with no HTN
Results
904 kidney donors with high BP (BP 140/90 or more or on anti-hypertesives) compared to 7817 doors with normal BP (BP <140/90). Follow-up duration was 14.3-+ 10.1 years and 16.6-+ 10.7 respectively
Hypertensive donors were older, mostly men and white, less relation to the recipient, and mostly educated with a lower eGFR
Additional 2319 donors developed HTN years after donation (were younger at donation,), less likely to be related to the recipient, had a higher baseline eGFR, a lower BMI, and were less likely to have a first-degree relative with HTN
After follow-up of donors with HTN and donors without HTN, similar proportion of CVD, DM, and ESRD. Hypertensive donors had a significantly higher serum creatinine level but eGFR was comparable in donors with and without hypertension
When compared donors with the new definition of HTN to non-hypertensive donors, they had comparable renal outcome but were more likely to die, were more likely to develop, and were more likely to develop diabetes
The multivariable risk of mortality, CVD, and proteinuria were also comparable in normotensive and hypertensive donors. eGFR slope over time was similar in hypertensive and non- hypertensive donors
Strengths of the study: long duration, diverse ethnicity, and donors had ascertainable intermediate renal outcomes
Limitation of the study: Probably no standardization of how BP measurements were carried out at the 3 centers (white coat HTN may be included), percentage non-Hispanic white donors in the RELIVE study was significantly high (70%), and less Hispanic and Asian donors than what is observed nationally
Conclusion
No increase risk of mortality, CVD, or ESRD in Kidney donors with the old definition of HTN
Outcomes of donors with the current definition of HTN were the same but CVD were more likely to develop. About one-third of kidney donors developed HTN after donation
Most donor candidates with HTN, particularly white donors, can be considered for donation provided that subtle renal disease is ruled out and and no increase risk of future CVD
What is the level of evidence provided by this article?
Level 2 (retrospective cohort study)
Please reflect on the guidelines and refer to your practice.
We are not accepting hypertensive donors with the old definition (BP 140/90 or more) or on antihypertensives
Thank you
Will you change your practice based on this article?