2. A 46-year-old CKD 5 on HD for 5 years due to MPGN nephropathy. Received a kidney offer from her brother, 000 mismatch with no DSA. He is heavy smoker (30 cigarettes/day over the last 25 years). He gives a history of mild to moderate COPD with remission and exacerbation. All other work up investigations are satisfactory.
- How do you manage this case?
- What is the effect of smoking on the outcome of transplantation?
As the patient has moderate COPD, it is important to perform a chest CT and spirometry for lung staging before surgery so that any doubts about lung capacity are clarified. There is also a need for an echocardiogram to assess pulmonary hypertension and the possibility of any treatment.
Given this deeper pulmonary assessment, we could reassess their treatments.
Studies have already shown that kidney transplant recipients who are smokers have a higher cardiovascular risk and lower graft and patient survival expectancy.
Patient with hx of CKD5 on RHD ,moderate COPD and chronic heavy smoker :
At risk of peripheral vascular disease :
Duplex on Ilac vs
duplex on both lower limbs (arteries and veins )
Carotids duplex
COPD with hx of chronic heavy smoker :
Chest X ray
Pulmonary functions tests
At cardiac risk ( heavy smoker and on Hemodialysis )
ECG
ECHO ( for diagnosis of pulmonary hypertension )
non-invasive tests for coronary vessels for this patient like (Myocardial perfusion imaging with exercise –ECHO with exercise –ECHO with dobutamin )
Effect of smoking :
Current smokers had an increase in the severity of vascular intimal fibrous thickening on renal allograft.
A known risk factor for cardiovascular disease is smoking. Cardiovascular disease has been mentioned by Ponticelli et al. as the primary killer of renal transplant recipients.
Malignancy was the second greatest cause of mortality following transplantation, and there was a definite link between smoking and an elevated risk for several forms of malignancy
References:
Ponticelli C, Villa M, Cesana B, Montagnino G, Tarantino A. Risk factors for late kidney allograft failure. Kidney Int. 2002;62:1848–1854.
This is a patient on HDx for the past 5years due to MPGN and he is a heavy smoker over the past 5 years , moderate COPD with remission and exacerbations
His donor is his brother with 000 mismatch with satisfactory work up pre Tx
The recipient requires a specialist assessment by a pulmonologist as well as a cardiologist . Who will perform further assessment and precautions such as quitting smoking and a healthy life style
regarding chest condition : pulmonary function test , routine CXr as well as CT chest may be required
Regarding Cardiology assessment: the patient has multiple risk factors for CVS events especially heavy smoking index and COPD which may cause Pulmonary Hypertension and Corpulmonale (heart faliure) , so ECG , ECHO as well as stress test with the possibility of Angio if required.
Regarding MPGN ; the biopsy should be checked by consultant nephrologist to check for the possibility of recurrence .
smoking Is hazardous to the health and increased the risk for CVS morbidity and mortality as well as increasing the risk of malignancy.
Also heavy smoking has a high risk of graft faliure about 25 to 30 % as well as increasing risk of rejection and allograft fibrosis .
He has a few CAD risk factors (dialysis for more than a year, smoking) and should be evaluated.
Patient has MPGN which has the risk of 10 to 50% chance of recurrence in graft. Presence of heavy proteinuria and autoantibodies to the phospholipase A2 receptor (PLA2R) further increase the chance of recurrence in graft and to be evaluated
Counselling for recurrence of MPGN and to quit smoking to be advised
Cardiovascular disease is the leading cause of death after transplantation, and smoking increases the risk of developing it further
This a best match we can get so we proceed for transplant after screening of peripheral vessels and abdominal vessels for atherosclerosis due to this history of smoking
second test should be done is pulmonary function test to determine the severity of COPD to know if she is fit for general Anathsia or not
1.According to immunological risk : 000 mismatch without DSA,so he is at low immunological risk for rejection,either Basiliximab or thymoglobulin can be used for induction.
According to the history of native disease, MPGN is classified into immune complex mediated and C3 glomerulopathy, recurrence rate ranges between 20 to 48% and higher among living -related-donor kidneys, the patient should be informed about this risk .
According to smoking history:the patient is heavy smoker , should be counselled for cessation of smoking and he should be investigated to detect drawbacks of smoking ( cardiac assessment ECG,ECHO,MPI if indicated),(chest X ray and pulmonary function tests,ABG) and peripheral artery disease( aorto-iliac Doppler ultrasound , non -contrast CT imaging for lower limb vessels)
According to history of mild to moderate COPD
Mild to moderate COPD is not contraindication for kidney transplantation, but the patient need some investigation to assess the pulmonary risk,which include history and physical examination,pulmonary function test,ABG,chest radiographs, cardiopulmonary exercise testing and ECHO to assess pulmonary artery pressure ( as irreversible moderate to severe pulmonary hypertension is a contraindication for transplantation), the patient should be encouraged to stop smoking.
2.Effect of smoking on the outcomes of transplantation
Active smoking has a negative outcome on the allograft survival. Kidney transplant outcomes are poorer in smokers versus non- smokers, the observed relative risk for graft loss is 1.3 to 2.3 among smokers. Moreover, cessation of cigarette smoking for 5 years before transplantation has a 34% relative risk reduction for graft loss.
Cigarette smoking is also a risk factor for lung and bladder cancer and vascular renal problems post renal transplantation.
Case analysis
Ø Young lady, relatively long dialysis time
Ø Primary kidney disease MPGN
Ø Heavy smoker
Ø High cardiovascular risk despite young age due to smoking and dialysis
Ø COPD
Ø Immunological match is satisfactory no mismatch and no DSA
She need MDT with pulmonologist, cardiologist, anaesthetist
So general workup, smoking cessation program is mandatory
Counsel about recurrence risk of MPGN
Assessment of cardiovascular with ECG, echocardiography, myocardial perfusion imaging.
Assessment of respiratory with ABG, chest x ray, CT chest, PFT, CPET
This figure demonstrates the effect of smoking on transplantation
Montgomery, R.A., Tatapudi, V.S., Leffell, M.S. et al. HLA in transplantation. Nat Rev Nephrol 14, 558–570 (2018).
Kidney transplant is the best RRT for ESRD patients regarding morbidity, mortality, and quality of life. recipient assessment pretransplant includes immunological and nonimmunological workup.
This donor received a kidney offer from her brother, 000 mismatches with no DSA: regarding immunological risk: this is low-risk kidney transplantation which can be done with induction steroids only with or without nondepleting induction with basiliximab followed by triple maintenance including tacrolimus, MMF and steroids.
Regarding her 1ry kidney disease which is MPGN nephropathy. The new classification as shown in the picture based on Immuno-peroxidase microscopy into 2 main categories immunocomplex mediated which is associated with a risk of recurrence of around 30-50% post-transplant and complement-mediated only which is associated with around 50-80% risk of recurrence and if recurred commonly it will cause graft loss. So, both donor and recipient should be counseled about this issue
Finally, she is a heavy smoker (30 cigarettes/day over the last 25 years). she should be assessed carefully regarding heart, chest, and peripheral vascular disease.
Regarding cardiological assessment: she is asymptomatic, below 50y, not a diabetic nor hypertensive but a heavy smoker so I will consider her high risk to be evaluated by ECG, ECHO heart, and MPI.
Regarding chest assessment: after pulmonology assessment, she will need to pulmonary function test pretransplant
Regarding peripheral vascular disease: still, invasive arteriography is the gold standard but I will go with CT angiography on abdominal and pelvic blood vessels and to assess by vascular pretransplant.
After the transplant, she should be counseled regarding smoking cessation as smoking is considered an independent risk factor of all causes of mortality and an increase of 50% of graft loss in 5 years post-transplant.
Reference:
Larry A Weinrauch et al. Smoking and outcomes in kidney transplant recipients: a post hoc survival analysis of the FAVORIT trial: international journal of nephrology and renovascular disease; 27 April 2018: Volume 11 Pages 155—164.
Multidisciplinary team approach is required should include pulmonologist, cardiologist and transplant nephrologist.. Patient should be counselled about the recurrence rate of MPGN (according to the type of MPGN) and risks with smoking and COPD and risk of allograft failure .Smoking increases the possibility of malignancy and later pulmonary complication including pulmonary hypertension and infections. Smoking quitting before transplantation is advised to reduce complications. First, detailed history and examination followed by needed investigations; CXR , PFT, ABG , ECG, Echocardiography, CPET, doppler U/S of limbs and CT angio if needed.
Long-time smoking has serious complications post transplant ; cardiovascular morbidity and mortality ,malignancies in addition to graft failure. It was found that recipient who smoke for more than 25years have almost 30% risk of graft failure.
– Weinrauch LA , Claggett B, Liu J , Finn PV, Weir MR, Weiner DE,etal.,Smoking and outcomes in kidney transplant recipients: a post hoc survival analysis of the FAVORIT trial,2018 Volume 2018:11 Pages 155—164
– Rosenkranz S, Howard LS, Gomberg-Maitland M, Hoeper MM. Systemic Consequences of Pulmonary Hypertension and Right-Sided Heart Failure. Circulation. 2020 Feb 25;141(8):678-693
· Q1: she should be consulted about the recurrence rate of MPGN after TX. To evaluate his condition, full history and Ph.E should be taken in addition to CXR, chest CT scan, PFT, o2 saturation, ABG and cardiologic investigation. He should stop smoking at least one month prior to TX and quit smoking for good after the TX.
· Q2: smoking is associated with increased risk of cardiovascular disease, malignancy and loss of graft function. This risk will be reduced by quitting it.
1- This patient should be counselled for:
· Possibility of Recurrence of MPGN post-transplant
· To stop smoking, he can be directed to smoking secession programs
· Should be investigated for fitness in regard to pulmonary disease. Should be referred to pulmonologist. Pulmonary function tests or computed tomographic examination should be conducted.
2- Cigarette smoking does adversely influence kidney transplant recipients, leading to cardiovascular disease, impairment in allograft function and increased risk of malignancies. Though published studies are small, the results consistently showed a strong relationship between cigarette smoking and reduced patient and graft survival.
Tobacco and cigarette smoke might cause microvascular alterations in the transplant vasculature leading to decreased renal plasma flow, enhance platelet aggregation, reduced the vasodilator endothelial nitric oxide generation, increased synthesis of endothelin-1, increased free radical production and accelerates atherosclerosis. Chronic cigarette smoke also increases proteinuria. Moreover, nicotine potentiates the sympathetic nervous system, leading to acute renal vasoconstriction, which is reported to be permanent in smokers.
Zitt et al. in their analysis of allograft biopsies of different chronic transplant smokers had demonstrated histological changes in kidney allografts when smoking had persisted after transplantation, in the form of vascular fibrous intimal thickening, which may act as a possible factor for the development of chronic allograft nephropathy. The overall quantity of cigarettes packs smoked annually at the time of transplantation remained a better prognostic factor for graft loss; since smoking of 25 pack/years or more (in comparison to a lesser amount or no smoking at all) was concurrent with an increased risk of graft failure by 30%. It is quite possible that smoking affects graft survival through an increase in mortality due to cardiovascular disease, while there was no association was found concerning smoking and the rate of acute rejection episodes at post-transplant which appears like non-smokers’.
References:
1. Nourbala M, Nemati E, Rostami Z, Einollahi B (2011) Impact of cigarette smoking on kidney transplant recipients: A systematic review. IJKD 5: 141-148.
2. Zitt N, Kollerits B, Neyer U, Mark W, Heininger D, et al. (2007) Cigarette smoking and chronic allograft nephropathy. Nephrol Dial Transplant 22: 3034-3039.
3. Kheradmand A, Shahbazian H (2005) The role of pretransplant smoking on allograft survival in kidney recipients. UNRC/IUA 2: 36-39.
4. ERBP (2016) ERBP Guideline on kidney donor and recipient evaluation and perioperative care. Draft 7 – Plain Text Version. Available at: http://www.european[1]renal-best-practice.org
How do you manage this case?
Good offer with 000 mismatches and no DSA, so it is a transplantable case
Multidiscipline approach is required including nephrologist, cardiologist and pulmonologist
Obstacles:
Original primary disease: MPGN which has a high recurrence rate post-transplant (25-60% in different studies)especially if living donor , and if cause monoclonal gammopathy , pre-emptive transplantation. Therefore, proper counseling is required together with careful monitoring of patient post-transplant for new/increasing proteinuria, hematuria, hypertension or acute allograft dysfunction. Knowing that MPGN is a histological description and not a disease entity, underlying the cause should be investigated (immune complex mediated or complement mediated) especially the donor is the brother. So, there could be a genetic factor considering C3,DDD.
Smoking: Smoking is not an absolute contraindication to transplantation. However, smoking carries much higher risk of CVD,PVD, malignancy and post-operative complications. Accordingly, all the transplant community should focus on the recipient and donor smoking cessation programs as well as proper chest physiotherapy.
COPD: It can result in chronic hypoxia and inflammation which may result in pulmonary hypertension and RVH which eventually leads to right heart failure with systemic congestion and fluid overload. So, perioperative cardiopulmonary assessment is necessary. Required tests include chest X ray, HRCT PFTs together with the meticulous cardiovascular system assessment.
What is the effect of smoking on the outcome of transplantation?
Smoking is independently associated with increase all-cause mortality, death with a functioning graft, post-transplant CVD, microalbuminuria, cancer risks, respiratory complications, ischemic strokes, PVD, besides 2 folds, increase in the risks of graft failure, and immunosuppression aggravates those risks.
Smoking cessation improves graft survival, but the effects on patient survival is unclear. Moreover, it was found surprisingly that donor smoking can impact the recipient survival years later after transplantation. The effects of smoking appear to dissipate 5 years after quitting. These results suggest that greater efforts is required to encourage patients to quit smoking before transplantation to reduce morbidity and mortality.
References:
1. Devresse A, et al. How to manage cigarette smoking in kidney transplant candidates and recipients?, Clinical Kidney Journal, Volume 14, Issue 11, November 2021, Pages 2295–2303.
2. Aref A, Sharma A, Halawa A. Smoking in Renal Transplantation; Facts Beyond Myth. World J Transplant. 2017 Apr 24;7(2):129-133.
3. Rosenkranz S et al Systemic Consequences of Pulmonary Hypertension and Right-Sided Heart Failure. Circulation. 2020;141:678–693.
This patient will require
Effect of smoking on transplantation:
” Cigarette smoking was an independent risk factor for patient death. In addition, on univariable and multivariable analyses, graft survival correlated with a history of cigarette smoking and the relative risk for graft failure ranged from 1.06 to 2.3.”
Nourbala MH, Nemati E, Rostami Z, Einollahi B. Impact of cigarette smoking on kidney transplant recipients: a systematic review. Iran J Kidney Dis. 2011 Jul;5(3):141-8. PMID: 21525572.
So, Smoking leads to increased patient and graft loss.
Management
1) Family conference. To establish the understanding of the potential harm of smoking to general health and potential risk of transplant failure.
2)Refer smoking cessation clinic.
3)Co manage with respiratory physician for proper respiratory function investigation such as pulmonary function test, lung perfusion scan . May need the help from intervention cardiologist for right heart study to exclude pulmonary hypertension. Intensified the treatment of LAMA / LABA for COPD.
Effect of smoking on the outcome of transplantation.
smoking potential stimulate memory T or B cell memory and accelerates allograft rejection.
Reference :
1) Qiu F, Fan P, Nie GD, Liu H, Liang C-L, Yu W and Dai Z (2017) Effects of Cigarette Smoking on Transplant Survival: Extending or Shortening It? Front. Immunol. 8:127. doi: 10.3389/fimmu.2017.00127
How to manage this case
Low immunologic risk transplant offer from her brother with 000 mismatch, no DSA.
High risk factors for graft loss in this scenario include the following:
1- Primary renal disease is MPGN with high post TX recurrence rate >50%.
2- Heavy smoker (37.5 pack/year) patient with COPD and possible smoking related complications like hidden malignancy, peripheral vascular disease, cardiovascular disease, pulmonary hypertension
Pre-transplant counselling is mandatory including all the above mentioned aspects of being high risk:
1- Recurrence rate of primary disease to be discussed with both donor and recipient.
2- Assessment of respiratory function by CXR, CT-chest, pulmonary function tests, respiratory physician clearance.
3- Assessment of cardiac function by ECG, ECHO, CPET, tight BP control, statins and cardiologist clearance.
4- Assessment of lower limb vascular circulation.
5- Rule out hidden malignancy because long smoking history.
6- Smoking cession advice.
I will go ahead with kidney transplantation unless there is an absolute contra-indication of kidney Tx.
Low immunological risk RTx offer directs immunosuppression to Basiliximab as induction agent, and low dose of sterois+ MMF+ CNI as maintenance.
1- Smoking >25 pack/year was associated with a 30% higher risk of graft loss.
2- Smoking was associated with increased risk of death post RTX.
3- Smoking is a risk factor for CVD, malignancy.
4- Smoking is associated with higher per-operative complications
As he is Smoker and having COPD with remissions and exacerbation, He need evaluation with Pulmonary function test, computed tomography of chest, ABG, 2DECHO to look for Pulmonary arterial Hypertension and cor-pulmonale.
He should be encouraged to discontinue the smoking since it increases the risk of allograft loss and patients death.
According to KDIGO Guidelines 2020
The patients having following features should not be the candidate for kidney transplantation.
a FEV1 < 25 % of predictive value
b PaO2 <60 mmHg at room air with exercise desaturation of < 90 %
c More than 4 LRTI in last 12 months and / or
d Moderate disease with progression
Effet of smoking on outcome of transplantation
In one study, patients with a 25-pack-year smoking history at the time of transplantation had a 30 % higher risk of allograft failure than those who either had never smoked or had smoked less. In addition, patients who had quit cigarette smoking more than five years prior to transplantation had a 34 percent lower relative risk of graft failure. The enhanced risk of graft failure among smokers was largely due to increased patient death.
This patient has mild to moderate COPD, & he is a heavy smoker for the last 25 yrs, all other investigations work up was satisfactory, so this patient needs PFT, a CT scan chest to evaluate pulmonary function & exclude any lung malignancy.
should counsel the patient about the risk of smoking for the graft & patient survival. Encourage stopping the smoking pre-transplant, needs pulmonologist evaluation, & he is at risk of pulmonary infection post-transplant, which increases hospital stay & morbidity.The effect of smoking on the outcome of transplant, increase graft loss.So smoking cession was advisable especially with this patient with MPGN nephropathy, with high risk to recur post-transplant
This patient had history of heavy smoking for >25 years with evidence of COPD, so he need the following:
All these measures should be done to reduce post-operative complications that can lead to prolonged hospital stay with subsequent increase in morbidity & mortality.
Renal transplantation shout not be offered for patient with:
Heavy smokers >25 pack-year found to be associated with 30% increased risk of graft failure & this risk reduced if the recipient stop smoking 5 years before transplantation. So smoking cessation is strongly advised fro transplant candidates & recipients as well.
References:
KDIGO Transplantation Guidelines 2020.
1- How do you manage this case?
Although this patients age is less than 50 years but still considered high risk group for perioperative cardiovascular complication because
1- Long duration hemodialysis .
2- Heavy smoker
The presence of mild to moderate COPD although it is not contraindication but but perioperative respiratory complication will be high like complication of general anesthesia , difficulty in extubation, difficulty in weaning of mechanical ventilation.
The underlying cause is MPGN pattern with different underlying cause the important one in this situation is ( C3 glomerulopathy , DDD ) as they has high recurrence rate post transplantation and may need specific management .
Management lines
History :
– Chest pain , intermittent claudication, uncontrolled blood pressure , respiratory status , family history of renal failure , ….
Exam :
Directed to exclude vascular complication , smoking related complication like ca lung .
Invest:
All investigation like other recipient . especially to exclude cardiovascular disase .
Specifically for CXR, chest CT scan ( to exclude malignancy ), pulmonary function test , ECG , ECHO assessment .
Exclude hereditary cause of MPGN ( complement factor defects )
CPET may give us a general physical performance assessing cardiac ,respiratory, neuro musculoskeletal system
Management :
This patient has good offer with low immunological risk , 000 mismatch, no DSA .
Has no absolute contra indication for transplantation.
Multidisciplinary team management including pulmonologist to treat and control the COPD status .
Arrange for vaccination ( influenza , pneumococcal , sars cov 2 )
Patient advised for smoking cessation before operation for three to six month.
Because smoking associated with bad graft outcome .
2- What is the effect of smoking on the outcome of transplantation?
– smoking more than 25 pack-years at transplantation (compared to smoking less than 25 pack-years or never having smoked) was associated with a 30% higher risk of graft failure
– Having quit smoking more than 5 yr before transplantation reduced the relative risk of graft failure by 34%
– The increase in graft failure was due to an increase in deaths
– The relative risk for major cardiovascular disease events with smoking 11 to 25 pack-years at transplant was higher than that of smoking more than 25 pack-years was .
– The relative risk of invasive malignancies was higher in smoker .
– cigarette smoking is associated with an increased risk of death after renal transplantation.
1- Kasiske BL, Klinger D. Cigarette smoking in renal transplant recipients. J Am Soc Nephrol. 2000;11(4):753–759. [PubMed] [Google Scholar]
the patient needs to be evaluated by a cardiologist to exclude hidden IHDm as well, as by a pulmonologist to assess his COPD severity.
CT scan chest, PFT, and ABG are needed.
the patient should be counselled about smoking and its adverse effect on the graft and should be encouraged to stop smoking before transplantation.
it carries high adverse effect on the graft, as well on the patient survival
According to KDIGO guidelines :
1:pulmonologist review
2: CT chest before transplantation for current or former tobacco smoking > or = 30 pack-years
3: PFT in pt with respiratory symptoms or respiratory disease
4:to avoid tobacco smoking prior to TX
5:Exclude patients with severe irreversible obstructive or restrictive lung disease from kidney transplantation
Effect of smoking on kidney transplantation :
Smoking after transplantation is associated with poor outcomes in both the short and long term after kidney transplantation.
• There is high quality evidence that smokers have an increased risk of perioperative respiratory complications.
• There is high quality evidence that people who smoke have an increased risk of CVD, non-skin malignancy, and death after kidney transplantation compared to
non-smokers.
• There is high quality evidence that smoking cessation
programs are more likely to result in patients stopping
smoking compared to no intervention.
• There is moderate quality evidence that an annual low-
dose computed tomography (CT) scan of the chest ver- sus a chest x-ray for 3 consecutive years reduces the risk of death from lung cancer and all-cause mortality in patients in the general population who have at least a 30 pack-year history of smoking.
According to KDIGO 2020 guidelines which suggest the patient with following clinical features should not be candidate for kidney transplantation.
Hence i would like to evaluate him further with 2DECHO and PFT.
and he should be counselled regarding recurrence of MPGN after renal transplantation.
Effect of smoking on outcome of transplantation.
According to study by Kasiske BL et al, published in J Am Soc Nephrology 2000; 11(4):753 they found that
After adjusting for multiple predictors of graft failure, smoking more than 25 pack-years at transplantation ( compared to smoking less than 25 pack-years or never having smoked)was associated with a 30 % higher risk of graft failure. ( RR- 1.30).
Having quit smoking more than 5 years before transplantation reduced the relative risk of graft failure by 34 %.
How do you manage this case?
Management of the patient (recipient) who is less than 50 yrs, will include laboratory investigations FBC, renal function and liver function, cardiovascular screening including ECG and echocardiography. CXR, viral screening including hepatitis B and C and HIV and cmv, BK and EBV.TB screening. Mammography and uss/ct abdomen.
The patient
· Age less than 50
· Ckd stage 5
· Native disease: mpgn
· Ooo mismatch
Good candidate for transplantation with low risk for surgery, however having had MPGN carries high risk of recurrence of the disease, and she should be informed about that. especially the transplant is live related.
The donor:
1. Excellent immunological match
2. No DSA
3. Heavy smoker
4. Mild to moderate COPD
The donor is high risk for procedure being heavy smoker and gets recurrent exacerbation of COPD. Risk of anesthesia , risk of hypertension, risk of ckd, risk of chest infection. most importantly risk of cardiovascular disease.
He should be screened for his cardiovascular disease with ECHO in addition to CXR, CT chest and CT renal vessels, in view of his heavy smoking. He will be prone for pneumonia which is considered the 3rd most common infection in the donors safter UTI and wound infections.
he should be advised to stop smoking for at least 6 week, Cigarette smoking causes increased bronchial secretion and impaired mucociliary clearance and this reduce after 6 wks of stopping smoking.(1)
Donors who are also Smokers reported to have significantly higher death rate among kidney donors who were smokers (2), were found to have higher serum creatinine at end of 1 year as compared to nonsmokers(3).
What is the effect of smoking on the outcome of transplantation?
Larry A Weinrauch et al 2018 ,reported in a Post hoc of FAVORIT study that smoking was associated with 100% increase in hazard of non-cardiovascular death, 50% increase in allograft failure.(4)
Smoking was associated with a 30% higher risk of graft failure , Having quit smoking more than 5 yr before transplantation reduced the relative risk of graft failure by 34% . The increase in graft failure was due to an increase in death . However,The effects of smoking appear to vanish 5 yr after quitting.(5).the study did show that Smoking did not have any effect on the rate of return to dialysis or on serum creatinine during the first year after transplantation.
1- J. R. Smith and S. A. Landaw, “Smokers’ polycythemia,” New England Journal of Medicine, vol. 298, no. 1, pp. 6–10, 1978.
2- D. L. Segev, A. D. Muzaale, B. S. Caffo et al., “Perioperative mortality and long-term survival following live kidney donation,” JAMA – Journal of the American Medical Association, vol. 303, no. 10, pp. 959–966, 2010
3- Heldt, R. Torrey, D. Han et al., “Donor smoking negatively affects donor and recipient renal function following living donor nephrectomy,” Advances in Urology, Article ID 929263, 2011.
4- Larry A Weinrauch, Brian Claggett,Jiankang Liu,Peter V Finn, Matthew R Weir,Daniel E Weiner, and John A D’Elia. Smoking and outcomes in kidney transplant recipients: a post hoc survival analysis of the FAVORIT trial. Int J Nephrol Renovasc Dis. 2018; 11: 155–164.
5- BERTRAM L. KASISKE and DAGMAR KLINGER. Cigarette Smoking in Renal Transplant Recipients. ASN April 2000, 11 (4) 753-759; DOI: https://doi.org/10.1681/ASN.V114753
An MPGN pattern of injury may result from multiple causes including infection, autoimmune diseases, monoclonal gammopathies, and complement dysregulation. In addition, an MPGN pattern of injury may occur in the absence of an obvious cause (adiopathic MPGN). Among patients who undergo transplantation, idiopathic MPGN and MPGN resulting from complement dysregulation commonly recur so this patient need to know form previous renal biopsy report which type of MPGN. Patients with MPGN that is secondary to infection, autoimmune disorders, and monoclonal gammopathies are generally not eligible for transplantation, unless the underlying cause is addressed.
observed recurrent disease in 67%–84% patients, with a median time to recurrence of 14–28 months. In the Mayo Clinic series, half of the patients with recurrent disease developed allograft failure at a median of 18 months after diagnosing recurrent C3 glomerulopathy. No data exist to support an association between complement testing and recurrent disease after transplantation .
cigarette smoking by living kidney donors significantly reduced recipient survival. So careful attention to smoking history is an important clinical measure in which to counsel potential donors and recipients. Policy efforts to limit donors with a recent smoking history should be balanced with the overall shortage of appropriate kidney donors. For this patient :should counselling recipient and donor and explain risk of smoking in recipient survival;.
References
1-Impact of cigarette smoking on kidney transplant recipients: a systematic review
Mohammad Hossein Nourbala 1 , Eghlim Nemati, Zohreh Rostami, Behzad Einollahi
2-: Treatment of C3 glomerulopathy in adult kidney transplant recipients: A systematic review. Med Sci (Basel) 8: 44, 2020
Google Scholar
1.
46 y old female end stage renal disease on regular haemodialysis due t MPGN received offer from her brother with 000 mismatches with no DSA , but he is heavy smoker and gave history of mild to moderate COPD with remission and exacerbation
Effect of smoking:
Smoking has deleterious effects decreasing both the graft survival and patients survival
The most common cause of mortality post transplant is cardiovascular disease and smoking is known for the negative effects on the cardiovascular system in terms of atherosclerosis, tachycardia and cardiovascular and cerebrovascular accidents.
Two important issues here
MPGN having high recurrence rate in the graft, needs proper counseling. Next one is mild to moderate COPD with heavy smoking.
Need to do pulmonary function test, CPET, evaluation of detailed cardiovascular and peripheral vascular system.
Need to adopt smoking cessation strategy.
Effect of smoking:
– Reduce patient survival
– Reduce graft survival
– Cardiovascular morbidity and mortality
– Increased risk of malignancy
Regarding the recipient:
need to evaluate for the basic disease as MPGN could be immune complex mediated which can be due to infections, lymphoproliferative disorders and autoimmune disease.
it can be complement mediated which may be c3 glomerulopathy( c3GN and DDD). MPGN can also be seen in TMA that is both non immunoglobulin and non complement mediated.
MPGN recurrence post transplant is about 50-80%. C3 glomerulopathy usually causes a chronic graft dysfunction. If it’s complement mediated genetic work up should be done. Ideally unrelated donor should be considered.
with regards to donor, he is a smoker. Smoking causes endothelial dysfunction and proteinuria and also reduction in eGFR. Also he would need pulmonology consultation and PFT
MPGN carries up to 50% recurrence rate post transplant , the risk is increased in cases of :
Low complement levels
Monoclonal gammopathy
Living related donor
The patient should be informed about the recurrence issue .
The donor should be properly assessed through pulmonologist , cardiologist as well as the recipient for sure through multidisciplinary team
More information about the MPGN pathology is needed to be known , C3 or IgG ? , Is there an EM examination for the biopsy done
Smoking has deleterious effects decreasing both the graft survival and patients survival
The most common cause of mortality post transplant is cardiovascular disease and smoking is known for the negative effects on the cardiovascular system in terms of atherosclerosis, tachycardia and cardiovascular and cerebrovascular accidents.
the recipient was on HD because of MPGN.
MPGN is a histological pattern of glomerular injury further subdivided into immune complex-mediated which is usually secondary and rarely idiopathic and C3 mediated either C3GN or DDD so we need a more specific diagnosis of her MPGN and if feasible a kidney biopsy may be considered, as the risk of recurrence varies post-transplantation, for instance, immune complex form recurs in 25%-65% transplant recipients with 10%-33% risk of graft failure and recurrence risk also varies depending on underlying aetiology, for c3 GN the recurrence risk may exceed 50%, these risks need to be discussed with the patient.
The donor: is a heavy smoker so he will be subjected to further workup; CT angiography, lipid profile, pulmonary function test and pulmonology consultation, ECHO and cardiology consultation
and should be advised to stop smoking as it may be more hazardous to a solitary kidney.
In the post hoc survival analysis of the FAVORIT trial, they concluded that
“Continued smoking was associated with >100% increased risk of non-cardiovascular death, 70% greater risk of all-cause mortality and a 50% greater risk of graft loss, a risk not seen in former smokers. These findings confirm previous non-adjudicated observations that smoking is associated with adverse clinical outcomes and suggest that more emphasis should be placed on smoking cessation prior to kidney transplantation”.
This patient has Membranoproliferative glomerulonephritis (MPGN) it is an uncommon glomerular injury pattern characterized by mesangial hypercellularity, endocapillary proliferation, and capillary-wall remodeling. MPGN accounts for approximately 7 to 10 % of all cases of biopsy-confirmed glomerulonephritis
MPGN recurs at a high rate after kidney transplantation.
The risk of MPGN recurrence increases with preemptive transplantation, living related donation, low complement level, and the presence of monoclonal gammopathy. Recurrence of MPGN leads to allograft failure in half of the cases.
55 % of MPGN recurrences were diagnosed within the first year of kidney transplantation.
In the studies by Lorenz et al. and Green et al., all cases were diagnosed within 1.2 and 2.6 years of transplantation respectively.
In this patient no data avilable about the type of MPGN, Complement ,or medical history.
And she must be informed about the risk of recurrence especially with living related donor.
▪︎the donor is chronic heavy smoker
receiving a renal transplant from a smoker donor increases the risk of death for the recipient and carries a poorer graft survival compared to non-smoking donors.
Donor must be evaluated carefully regarding cardiovascular disease, atherosclerosis, duplex on renal vessels, malignancy, pulmonary function.
Ritz et al, studied the effect of smoking on healthy normotensive volunteers. They reported a significant increase in arginine vasopressin levels and serum epinephrine.
There was an increase in renal vascular resistance by 11% and a decrease in the glomerular filtration rate (GFR) by 15%.
They assumed these effects are secondary to nicotine itself as these findings were reproduced by using nicotine containing gum.
Although there is no clear contraindication for transplantation from a smoker but i prefer to find another donor due to high risk if recurrence of MPGN and risks associated with smoking.
▪︎What is the effect of smoking on the outcome of transplantation
Several studies have documented a deleterious effect of smoking on the renal transplant recipients most probably due to the chronic immune suppression status and the metabolic effect of the drugs.
Smoking was associated with lowering patient and graft survival.
The effect of smoking is aggravated in renal transplant recipients due to the effect of immune suppression medications on carcinogenesis,
in addition to the effect of chronic kidney disease itself on cardiovascular risk and mortality
The development of de novo cardiovascular insult in the first year post-transplant was associated with pre-existing cardiovascular disease, older age, pre-transplant hypertension, smoking and duration of dialysis.
The second leading cause of death post-transplantation was malignancy with a clear association between smoking and increased risk for certain types of malignancy
Smoking cessation proved to improve graft survival and to a lesser extent recipient survival.
Sami Alasfar, Naima Carter-Monroe, Nada Alachkar.Membranoproliferative glomerulonephritis recurrence after kidney transplantation: using the new clclassification.BMC Nephrology .17, Article number: 7 (2016)
Ahmed Aref, Ajay Sharma, and Ahmed Halawa.Smoking in Renal Transplantation; Facts Beyond Myth.World J Transplant. 2017 Apr 24; 7(2): 129–133.
A 46-year-old CKD 5 on HD for 5 years due to MPGN nephropathy.
First need to know cause of MPGN if as this affect recurrence and time of transplantation as some cause need to be treated first like infection and autoimmune disease .
patient need to concluded about recurrence of MPGN
uptodate 2018 (The overall reported rate of recurrent idiopathic MPGN is between 19 and 48 percent [17-27].
Denton MD, Singh AK. Recurrent and de novo glomerulonephritis in the renal allograft. Semin Nephrol 2000; 20:164.
Recurrence may be higher among recipients of living-related-donor kidneys, compared with deceased-donor kidneys.
He is heavy smoker and has COPD full evaluation by respirarory dr about persent state of COPD and to how extent respond to medical treatment and need surgical intervention at time being .
patient with COPD has higher risk of lung cancer so also need to counsel and
also increase risk of lung infection so need to be considered with Immunosuppression
cigarette smoking increase risk of lung cancer it self
cigarettes smoking is a strong risk factor for cardiovascular disease so need careful cardiac and cigarettes smoking is a strong risk factor for atherosclerosis so arterial vessel wall evaluation is needed
counsel about stop smoking is mandatory
CPET is essential to evaluate him physically
==================================================================
Effect of smoking on the outcome of transplantation
Impact of cigarette smoking on kidney transplant recipients: a systematic review
Mohammad Hossein Nourbala 1 , Eghlim Nemati, Zohreh Rostami, Behzad Einollahi
Affiliations
Conclusions: Cigarette smoking was associated with an increased risk of death and graft loss. Therefore, every attempt should be made to encourage kidney transplant candidates to stop smoking.
——————————————————————————————
Excess risk of renal allograft loss associated with cigarette smoking
R S Sung 1 , M Althoen, T A Howell, A O Ojo, R M Merion
Affiliations
Conclusions: Cigarette smoking before kidney transplantation contributes significantly to allograft loss. The effect of smoking on graft outcome is not explained by increases in rejection or patient death. Smoking cessation before renal transplantation has beneficial effects on graft survival.
These effects should be emphasized to patients with end-stage renal disease who are considering renal
————————————————————————————————-
Smoking Is Related to Postoperative Pulmonary Complications and Graft Outcomes in Renal Transplant Patients
Balam Er Dedekargınoğlu 1 , Gaye Ulubay, Elif Küpeli, Mahir Kırnap, Füsun Öner Eyüboğlu, Mehmet Haberal
Affiliations
Conclusions: Renal transplant patients who are smokers have an increased risk for early postoperative pulmonary complications. Furthermore, cigarette smoking contributes to allograft loss in renal transplant patients. Smoking cessation before surgery can reduce the risk of early postoperative complications.
46 year old lady with MPGN and CKD V on regular hemodialysis received a kidney offer from her brother with full match and no DSA. The donor is a smoker 30 cigarettes/day over the last 25 years. He has history of COPD with recurrent exacerbations and remissions…
Management of the case:
with regards to the recipient: She has a basic disease of MPGN. The issue with this disease is recurrence following renal transplant. If possible the MPGN needs to be further sub divided as C3 or Ig related.. C3 glomerulonephritis has a higher incidence of recurrence after transplant ; can range from 45-70%. The histolgical recurrence rate of C3 glomerulopathy is about 100%. If recurred the graft loss rate is 50% if not properly treated…the above needs to be counselled to the patients..
with regards to the donor:
The donor is a chronic smoker and has COPD. He has been labelled to have mild to moderate COPD. This is not a contraindication to renal donation. He needs to see a pulmonologist and do the PFT. He needs to be on bronchodilators pre and post transplant. In view of chronic smoking we also needs to see and assess the cardiovascular burden. ECG, 2D Echo and a thorough cardiac assessment is needed…Arterial doppler of the lower limbs and the aorta through a CT renal angiogram is needed to assess the donor before surgery…There could be significant plaques causing obstruction to a major artery which needs to be identified…The donor due to chronic smoking could have arteriolosclerosis inside the kidney. We need to do DTPA renogram before renal transplant to assess the overall GFR and split GFR…
Smoking effects on renal transplantation:
Smoking has a negative effect on the graft function.. cigarettes’ have nicotine which is a direct vasoconstrictor. There is upregulation of endothelin and decrease in the nitric oxide levels in chronic smokers…This leads to chronic graft dysfunction due to arteriolosclerosis and leads to decrease GFR. Smoking can increase the systolic blood pressure and is associated with increased cardiovascular mortality….
There are studies to show that donor smoking has negative impact on graft survival
Reference:
Aref A, Sharma A, Halawa A. Smoking in renal transplantation; facts beyond myth. World Journal of Transplantation. 2017 Apr 24;7(2):129.
46 y old female end stage renal disease on regular haemodialysis due t MPGN received offer from her brother with 000 mismatches with no DSA , but he is heavy smoker and gave history of mild to moderate COPD with remission and exacerbation
CPET for integrative assessment of cardiovascular, pulmonary, muscular and neuro- psychological responses dining exercise for assessment of physiological reservoir assessment which can’t be measured at rest.
What is the effect of smoking on the outcome of transplantation
-studies demonstrated that smoking negative effect of cardiovascular nonfatal and fatal events in whom at relatively low risk which increases with comorbidities like (renal, cardiovascular, respiratory, neurologic), obesity, hyperlipidemia, diabetes and hypertension.
– In kidney transplant recipients, the continuation smoking was seen in 11% of patients in the international FAVORIT trial. There was an adverse effect between smoking and continued smoking which can cause mortality . Despite there was an effect of smoking on cardiovascular , about two-thirds of kidney transplant patients died from causes not cardiovascular causes . The Current smoking was a 50% increase in the risk of allograft failure and a 60% increase in the risk of death and graft failure. So current smoking must considered a relative contraindication to limited resourced organs transplant.
•the smoking Carry risk of Increased blood pressure, reno-vascular , malignant and masked hypertension.
MPGN has about 50% of recurrence post-transplantation (1). this need to be explained to the patient. 25 years of cigarette 18 Pack/year is a very high risk from the cardiovascular point of view. not only cardiac but all vessels are affected, son this is expected to affect transplanted kidney arterial supply. except for lung transplantation, other solid organ transplantation is not contraindicated (2). Cigarette smoking has an adverse effect on renal function and found to cause a higher incidence of diabetes. Also was associated with vascular intimal fibrous thickening (3). The adverse effect on the immune system adds a risk of rejection. Last not least, the risk of cancer which is already higher in transplanted patients, will increase with ongoing cigarette smoking.
1- Alasfar, S., Carter-Monroe, N., Rosenberg, A.Z. et al. Membranoproliferative glomerulonephritis recurrence after kidney transplantation: using the new classification. BMC Nephrol 17, 7 (2016). https://doi.org/10.1186/s12882-015-0219-x
2- Anis KH, Weinrauch LA, D’Elia JA. Effects of Smoking on Solid Organ Transplantation Outcomes. Am J Med. 2019 Apr;132(4):413-419. doi: 10.1016/j.amjmed.2018.11.005. Epub 2018 Nov 17. PMID: 30452885.
3- Front. Immunol., 10 February 2017 Sec. Alloimmunity and Transplantation https://doi.org/10.3389/fimmu.2017.00127
4- Cigarette Smoking in Renal Transplant Recipients BERTRAM L. KASISKE, DAGMAR KLINGER JASN Apr 2000, 11 (4) 753-759; DOI: 10.1681/ASN.V114753
Background
Smoking is one of the preventable leading causes of death worldwide. many studies showed associations between smoking and cardiovascular disease, pulmonary diseases, malignancy, and death, However, the direct effect of smoking on the renal system was undermined.
several studies have documented the deleterious effect of smoking on renal transplant recipients.
How do you manage the case?
A multidisciplinary team is needed for different assessments, (nephrologist – pulmonologist, and cardiologist) during the pre-transplant work-up.
Concerning MPGN should explain to the patient the possibility of MPGN recurs at a high rate after kidney transplantation. increases in this case due to a live donor.
Smoking is not a contraindication for transplantation patient must stop smoking before transplantation, Pulmonary assessment including pulmonary function tests, CT chest and CPET, and refer to the pulmonology unit.
Been on HD for 5 years consider risk factors for cardiovascular disease so he needs cardiac assessment (ECG –ECHO-Noninvasive stress-test -etc.) depending on the finding.
Peripheral vascular assessment is essential
IF no contraindication such as lung disease requiring home oxygen therapy, uncontrolled bronchial asthma, severe cor pulmonale, irreversible moderate to severe pulmonary hypertension, and severe COPD, pulmonary fibrosis, or restrictive disease (2).
we can proceed to renal transplant.
What is The effect of smoking on the outcome of transplantation?
1. The risk of mortality after the first year was high.
2. Worse patient and graft survival and worse long-term outcome.
3. Contributes to graft loss but has no significant relation with rejection episodes
4. Smoking was associated with vascular fibrous intimal thickening in transplanted kidneys so it may have a role in the development of chronic allograft nephropathy and graft loss
5. History of smoking will negatively affect patient and graft survival. Also, it increases the risk of early rejection.
6. New onset smoking post-transplant associated with lower patient and graft survival
7. Donor smoking proved to have a negative impact on the graft survival.
REF:
1. Aref A, Sharma A, Halawa A. Smoking in renal transplantation; facts beyond myth. World Journal of Transplantation. 2017 Apr 24;7(2):129.
2. Knoll G, Cockfield S, Blydt-Hansen T, Baran D, Kiberd B, Landsberg D, Rush D, Cole E. Canadian Society of Transplantation: consensus guidelines on eligibility for kidney transplantation. Cmaj. 2005 Nov 8;173(10):S1-25.
Management:
The patient should be informed about the risk of recurrence of MPGN post transplant and that the risk increase with living related donor, low complement level and in presence of monoclonal gammopathy.
Regarding his chest condition, the patients should do CT chest to exclude presence of occult lung cancer, pulmonary function tests and should be referred to pulmonologist for further assessment.
He should be counseled to stop smoking at least one month before surgery and indefinitely after surgery
The patient is considered at high risk of cardiovascular disease, ECG, echocardiography to assess cardiac function and pulmonary artery systolic pressure and stress echocardiography to exclude IHD.
Peripheral arterial disease should also be excluded in this patient, history of claudication and CT of pelvic vessels
There are contraindications for transplantation including patients on home oxygen therapy, severe irreversible obstructive lung disease, severe cor-pulmonale and severe COPD with FEV1<25%
Effect of smoking on outcome if kidney disease:
Smoking is associated with increased mortality as it increase the risk of cardiovascular disease, the leading cause of death post-transplant
It is also associated with certain types of malignancies
It leads to poor graft survival due to endothelial dysfunction, vascular disease and atherosclerosis.
Remote past smoking may have less impact on graft survival.
Quitting smoking >5 years prior to transplantation was associated with less risk of graft failure due to smoking.
Smoking habit of kidney donor also affect the recipient long-term survival post-transplant.
Lentine KL, Kasiske BL, Levey AS, Adams PL, Alberú J, Bakr MA, Gallon L, Garvey CA, Guleria S, Li PK, Segev DL. KDIGO clinical practice guideline on the evaluation and care of living kidney donors. Transplantation. 2017 Aug;101(8 Suppl 1):S7.
Aref A, Sharma A, Halawa A. Smoking in Renal Transplantation; Facts Beyond Myth. World J Transplant 2017; 7(2): 129-133
Khalil MA, Tan J, Khamis S, Khalil MA, Azmat R, Ullah AR. Cigarette smoking and its hazards in kidney transplantation. Advances in Medicine. 2017 Jul 27;2017.
Thank You, Yes, it is not only the chest, bute we need to investigate other organ dysfunction
Hi Dr Heba Wagdy,
I like that you have considered the possibility of pulmonary HT in this case.
Ajay
First of all mild to moderate COPD is not an absolute contraindication for renal transplantation .
What is the effect of smoking on the outcome of transplantation ?
according to : https://pubmed.ncbi.nlm.nih.gov/27805521/#article-details
Renal transplant patients who are smokers have an increased risk for early postoperative pulmonary complications. Furthermore, cigarette smoking contributes to ALLOGRAFT LOSS in renal transplant patients. Smoking cessation before surgery can reduce the risk of early postoperative complications
I forget to say that CPET is the investigation of choice for this case ( if available )
thanks
Thank You, CPET is also an option as it tests the respiratory, cardiac, and muscle functions.
What is the effect of smoking on renal graft function?
increase risk of allograft loss
How do you manage this case.
MDT should be involved including pulmonologist, cardiologist and transplant physician. Patient should be counselled about the recurrence rate of MPGN according to the type of MPGN and risks associated with smoking and COPD and risk of allograft failure .Smoking also increases the chances of malignancy and patient also has problem with extubation and later pulmonary complication including pulmonary hypertension and infections. Patient should be advised to quit smoking before transplantation to reduce the burden of complications. Therefore, detailed history and examination followed by thorough investigations needed. (CXR , PFT, ABG ,chest XR, ABG, ECG, Echocardiography, CPET, doppler U/S of limbs and CT angio of vessels if needed).
What is the effect of smoking on the outcome of transplantation?
Smoking, if continued for long ,can have devastating complications post transplant i.e., cardiovascular morbidity and mortality ,malignancies and graft failure. According to one study ,recipient who smoke for more than 25years have almost 30% risk of graft failure,and Kasiski BL in his study mentioned about reduction of mortality aftero5 years of stopping smoking
REFERENCES:
1. Weinrauch LA , Claggett B, Liu J , Finn PV, Weir MR, Weiner DE,etal.,Smoking and outcomes in kidney transplant recipients: a post hoc survival analysis of the FAVORIT trial,2018 Volume 2018:11 Pages 155—164
2. Rosenkranz S, Howard LS, Gomberg-Maitland M, Hoeper MM. Systemic Consequences of Pulmonary Hypertension and Right-Sided Heart Failure. Circulation. 2020 Feb 25;141(8):678-693
Thank You
Well this reminds me of my previous fellowship that is the one organised through the Liverpool which has now been stopped. I was able to complete my first module in Masters in kidney transplantation organised by the Liverpool University and supervised by Professor Halawa. I was given a small project by Professor regarding the effects of cigarette smoking on renal transplantation and its outcome is post transplantation.
But sadly I have to opt out of the course due to some professional commitments.
before I move ahead to comment on the above scenario I would like to quote about a very beautiful article written by Professor Halwai Ajay Sharma and Ahmed Arif Ahmed was my colleague in In the previous course of Masters in kidney transplantation and we both were given the above topic to work together on that and complete the project.
Aref A, Sharma A, Halawa A. Smoking in Renal Transplantation; Facts Beyond Myth. World J Transplant. 2017 Apr 24;7(2):129-133. doi: 10.5500/wjt.v7.i2.129. PMID: 28507915; PMCID: PMC5409912.
How do you manage this case?
So, I would focus on the management pertaining to the chronic smoking habit of the recipient and that includes pre-transplant evaluation specially focusing on the existing complications and/or co-morbidities of various organ systems which the recipient might have during the pre-transplant period. This also includes the situation of smoking or minimising the smoking of the recipient post transplantation.
In such recipients evaluation should include the specific assessment Related to the complications of respiratory system, cardiovascular system, neuropsychiatric issues and assessing the possibility of any pre-existing malignancies secondary to chronic smoking.
in India we don’t have well-developed social medicine, and we don’t have a structured smoking situation program. So in the light of all this my approach in managing this case would include
Excellent
Evaluating this patient
1- Immunological risk is fair as he has living related donor with perfect HLA matching and no DSA
2- For his renal pathology : it needs to be revised and classified as either immune complex mediated or complement mediated , MPGN has recurrence rate between 15-65 % and 50% of recurrence ends in ESRD
3- Evaluating the impact of smoking on the patient as smoking is associated with premature and accelerated CV complications and atherosclerosis and increased risk of MI and stroke so needs thorough evaluation with ECG , Echo ( for systolic and diastolic dysfunction , pulmonary HPN presence and severity ) and need expert cardiologist evaluation
4- For atherosclerosis ( both smoking and long duration dialysis are risk factors ) : assess aorta and pelvic vessels with duplex or better with CT angiography
5- For COPD : chest consultation and CPET to assess functional capacity .
Thank You, this is a very short answer Fatima
How do you manage this case?
This 45 year old patient has excellent offer with 000 mismatch and no DSA. He will need careful assessment and planning of treatment. A multimodality approach will be adopted. He is also a risk for Cardiovascular disease. Mild to moderate risk respiratory patients can have renal transplant after optimisation while high risk patients cannot have renal transplant. KIDGO recommends cessation of smoking one month before being enlisted on transplant waiting list but does excludes smokers from transplantation.
I will seek help from Respiratory physician. He will need HRCT Chest and PFT-Pulmonary function tests.
I will do ECG, Echo and consult cardiologist who may consider CPET
He has to quit tobacco smoking indefinitely for which I will encourage him to join smoking cessation programme and pulmonary rehabilitation programme
After careful assessment a decision can be made about respiratory status and irreversibility can be excluded.
COPD needs to be optimized
Pneumococcal and COVID 19 vaccination
What is the effect of smoking on the outcome of transplantation?
Smoking is associated with high risk of cardiovascular disease, graft loss and non cardiovascular causes of deaths. Smoking is associated with higher morbidity and mortality. Those who quit smoking more than five years before transplantation have lower risk of graft loss.
Chronic smoker have higher tendency to be non compliant and should be kept in mind while managing such cases.
Smoking can affect Cytochrome P450 and may affect immune suppressants levels thus affecting graft outcomes due to rejections.
A multimodality approach targeting with active patient involvement is key to better outcomes.
References:
Bertram l. Kasiske and Dagmar Klinger. Cigarette Smoking in Renal Transplant Recipients. JASN April 2000, 11 (4) 753-759.Brian D Kent et al. The impact of chronic obstructive pulmonary disease and smoking on mortality and kidney transplantation in end-stage kidney disease. Am J Nephrol. 2012;36(3):287-95.
When do you refuse to transplant a patient with COPD.
In those with svere COPD requiring oxygen and associated pulonary hypertension
I would ask the patient to quit smoking, for at least 6 months prior to the transplant. Enrolling the patient in a smoking cessation program or referring him to a specialized clinic would help and increase the odds of being smoking-abstinent at the time of the intended transplantation. all this should be done after explaining the short and long term consequences of both previous exsmoking and active ongoing smoking on the transplant process. this all, after doing PFT and CPET, with satisfactory results suggesting to safely proceed to the transplantat surgery
regarding the effect of smoking on the outcome of transplantation, smoking is known to adversely affect patient and graft survivial. there is an increase in periopertive cardiopulmonary complications ( MACE, longer time on ventilator, postop pneumonia). In addition, there is an increased incidence of PAD, CAD, lung cancer, transplanted renal artery stenosis, stroke, and infective COPD exacerbations
Good.
This patient is obviously suffering from chronic obstructive pulmonary disease.which is usually associated with heightened intra-operative and post operative mortality and morbidity.
It was reported to be associated with increased incidence of pneumoinia, Resporatory failure , failure of ventilation weaning, re-intubation within 30 days .
Intra-operative complications include:
1) Bronchospasm due to monipolation with laryngoscopy, intra broncheal tube or inhalation,
2) hyperinflation.
3)Atelactasis resultant from diminishing FRC and abdomenal muscle contraction.during the induction.
4) Hypoventilation from residual sedation .
When would you refuse to transplant a patient with COPD.
Active respiratory infection.
Pulmonary hypertension.
respiratory failure , relative contraindication.
reference:
Rachil Budithi and Sylvia K Doliniski,anesthesia for patients with chronic obstructive pulmonary disease.Uptodate 2022.
Evaluation and approach:
Depending on the initial assessment and severity of pulmonary function impairment featured by FEV1 and FEV1/FVC.
The plan is to improve the base line pulmonary function and treat any COPD exacerbation or upper respiratory tract infection depending on the sputum culture testing and severity and reversibility of spirometry ..
The pivotal measures to be undertaken are primarily to stop smoking for 10 to 12 weeks prior to operation.
Vaccination against influenza ,Covid-19 and pneumococcal infection.
chest physiotherapy to optimize respiratory muscle strength and capacity.
bronchodilators {B agonist and anticholinergic] , inhaled corticosteroids and short course of pre-operative. oral corticosteroid .
Nutritional status has to be addressed as hypoalbuminemia is a bad prognostic factor for pulmonary function.
other co-morbidities that might worsen the pulmonary performance such as cardiac failure, atrial fibrillation , pulmonary hypertension has to be managed prior to the operation.
There is no prohibitive level of FEV1 at which surgey is contraindicated.
Other condition that might precipitate respiratory failure and higher morbidity and mortality :
Obstructive sleep apnea.
morbid obesity.
☆ How do you manage this case?
▪︎Counsel this lady about the importance of Cigarette smoking cessation before kidney transplantation.
▪︎ Assess her pulmonary function and treat accordingly.
▪︎ Assess her cardiac function.
▪︎ Investigate for vascular complication.
☆What is the effect of smoking on the outcome of transplantation?
▪︎ Both donor and recipient smoking have been shown to increase graft loss and mortality in solid organ transplant recipients in many studies [1].
▪︎Smokers have poorer outcomes after transplantation compared with non-smokers [2]. Also, the correlation between post-KT CVD and cigarette smoking has been demonstrated.
▪︎ Active smoking negatively impacts allograft survival, with reported relative risks of 1.3–2.3 for graft loss. Interestingly, quitting cigarette smoking for >5 years before KT was associated with a 34% relative risk reduction for graft failure. In addition, although former smokers have increased long-term graft and death-censored graft loss rates compared with never smokers, this association is much stronger in patients who restarted or continued smoking after kidneytransplantation [3].
▪︎Cigarette smoking is also a risk factor for post-KT invasive malignancies, mostly lung and bladder cancers. Ithas also been associated with vascular renal problems such as fibrous intimal thickening of small arteries and allograft rejection [3].
__________________________________________
Ref:
[1] Karim H Anis et al. Effects of Smoking in Solid Organ Transplantation Outcomes. Am J Med. 2019 Apr.
[2] Duerinckx N, et al. Correlates and outcomes of posttransplant smoking in solid organ transplant recipients: a systematic literature review and meta-analysis. Transplantation 2016; 100: 2252–2263
[3] Arnaud Devresse, Sophie Gohy, […], and Nada Kanaan. How to manage cigarette smoking in kidney transplant candidates and recipients?
What about CVD investigation and assesment.
We can evaluate this patient for the presence and severity of cardiac disease with history, physical examination, and Echo. If she has signs or symptoms of active cardiac disease should undergo assessment by cardiologist, and be managed according to local cardiac guidelines prior to further consideration for kidney transplantation.
_________
Ref:
KIDIGO guidelines
# How do you manage this case?
* The list of medical problems: CKD stage 5 and on HD for 5 years
MPGN
Heavy smoker
*The cardiologist and pulmonogist should be involved from the start with other MDT in pre transplant workup
*We should counseling the patient about:
** MPGN recurs at a high rate after kidney transplantation. The risk of MPGN recurrence increases with preemptive transplantation, living related donation, low complement level, and the presence of monoclonal gammopathy. Recurrence of MPGN leads to allograft failure in half of the cases.(1)
** (COBD) and the risk of smoming , so sessation of the smoking should be recommended for it is fatal complications (CVD, infecion, malignancies, rejection and death
* Clinical history and examination
*Investigation for full workupfor peripheral vacular disease, CA, IHD, COBD and pulmonary hypertension so ( rotune inves., CXR , PFT, ABG chest XR, ABG, ECG, Echocadiography, CPET doppler U/S
Then treated accordingly
# What is the effect of smoking on the outcome of transplantation?
* Smoking is a well-known risk factor for cardiovascular disease, which is the leading cause of death in renal transplant recipient.
* The development of de novo cardiovascular insult in the first year post-transplant was associated with pre-existing cardiovascular disease, older age, pre-transplant hypertension, smoking and duration of dialysis.
* The second leading cause of death post-transplantation was malignancy with a clear association between smoking and increased risk for certain types of malignancy.
* The effect of smoking on renal transplant recipients was investigated in relatively few studies, and most of them are retrospective.
*Current smokers had an increase in the severity of vascular intimal fibrous thickening (P = 0.004). While the degree of chronic sclerosing nephropathy (P = 0.05) and arteriolar hyalinosis (P < 0.001) were associated with the duration of time post-transplantation.
* Most of these studies have revealed a clear benefit of smoking cessation on graft survival, but the effect on patient survival is less clear possibly reflecting the permanent atherosclerotic effect on the vascular system.
* Lin et al. Conducted that smoking habit of the donor has mild, yet statistically significant effect on recipient survival (HR = 1.06, P < 0.05), and graft survival (HR = 1.05, P < 0.05).(2)
# References
(1) Alasfar S, Carter-Monroe N, Rosenberg AZ, Montgomery RA, Alachkar N. Membranoproliferative glomerulonephritis recurrence after kidney transplantation: using the new classification. BMC Nephrol. 2016 Jan 11;17:7. doi: 10.1186/s12882-015-0219-x. PMID: 26754737; PMCID: PMC4709883.
(2) Aref A, Sharma A, Halawa A. Smoking in Renal Transplantation; Facts Beyond Myth. World J Transplant. 2017 Apr 24;7(2):129-133. doi: 10.5500/wjt.v7.i2.129. PMID: 28507915; PMCID: PMC5409912.
Exellent.
Regarding MPGN , There is increased risk of recurrence post-transplantation up to 60% , especially if living donor , and if cause monoclonal gammopathy , pre-emptive transplantation.
Smoking had bad impact on renal transplantation, increasing mortality by elevating the risks of cerebrovascular as well as cardiac events leading to death with functioning graft. Also it leads to increased risk of cancer lung.
Smoking is considered more dangerous in renal transplant patients. smoking associated with >100% increased risk of non-cardiovascular death, 70% increased risk of mortality and a 50% greater risk of graft loss, a risk not seen in former smokers.
Patient should be evaluated by cardio-pulmonary tests as; CPET.
smoking also has effects on donor : more preoperative complications, and delay post- operative wound infections , high incidence of death rate.
Refrences: 1. Weinrauch LA , Claggett B, Liu J , Finn PV, Weir MR, Weiner DE,etal.,Smoking and outcomes in kidney transplant recipients: a post hoc survival analysis of the FAVORIT trial,2018 Volume 2018:11 Pages 155—164
2.Muhammad Abdul Mabood Khalil, Jackson Tan, Said Khamis, etal.,:Cigarette Smoking and Its Hazards in Kidney Transplantation, Hindawi ,Advances in Medicine , Volume 2017, Article ID 6213814.
Very good.
ESRD (MPGN) 5 Yrs on hemodialysis, active smoker, COPD. living donor with a good match, and no DSA
1- he is at risk of MPGN recurrence, especially LD.
MPGN recurrence rate post-transplant is high although it varies between studies (25% — 60%) and factors that increase its recurrence are LD, preemptive transplantation, monoclonal gammopathy, and low complement. if he has heavy proteinuria might need a native nephrectomy. it is better if we can determine the type of MPGN (C3 might need further work ).
s he is COPD case, he needs pulmonologist consultation and cardiologist consultation. PFT, CXR, functional status assessment with CPET.
thought history and examination looking for any vascular disease (intermittent claudication) and may ct angiography for the iliac vessel.
counselling regarding smoking cessation.
effect of smoking on the graft?
it increases the risk of graft loss and cardiac events.
very good.
when do you consider a contrindication ( pulmonary wise ) to transplant her.
How do you manage this case ?
MPGN is uncommon glomerular disorder that may lead to end stage kidney disease and excellant candidate for transplantion .
.follow up pulmonologist to evalauted pulmonary function and CPET
What is the effect of smoking on the outcome of transplantation?
Continued smoking was associated with >100% increased risk of non-cardiovascular death, 70% greater risk of all-cause mortality and a 50% greater risk of graft loss, a risk not seen in former smokers. These findings confirm previous non-adjudicated observations that smoking is associated with adverse clinical outcomes and suggest that more emphasis should be placed on smoking cessation prior to kidney transplantation.
management comprises :
investigations .
decision taking as who to transplant and who is a contraindication to transplant.
This patient is considered a high risk patient based on the following:
Primary renal disease : MPGN has a high recurrence rate post renal transplant up to 50% , also needs specific meticulous cost preparation based on the immunological aspect ( may need induction by eculizumab), better to avoid also high matched donor being higher risk of recurrence.
History of long duration of cigarette smoking predisposes to multiple vascular diseases; advances atherosclerosis all over the body most important carotid vessels, coronaries, even renal vessels increasing the incidence of cerebrovascular events up to stroke, cardiac ischemia as well with high susceptibility to MI, also smoking affects the lung capacity and respiratory reserve function negatively.
History of COPD, besides recurrent attacks of exacerbations needs strict prophylaxis against such episodes which would be hazardous post transplantation under the effect of high immunosuppressive regimen owing to the MPGN as the primary disease.
Smoking also may be associated with dyslipidemia and HTN raising the complications that ought to be controlled pre and post transplantation tightly.
Smoking itself carries the risk of renal graft failure estimated by 30 %, mortality with functioning graft and increased risk of malignancies as a whole.
Long duration of haemodialysis per se exposes the patient to cardiovascular complications more than the regular population.
So, patient counselling is very mandatory highlighting the previously mentioned data, and ensuring the necessity of quitting smoking and adopting a healthy lifestyle to improve the outcome of this renal transplant candidate.
A multidisciplinary team should be one of the cornerstone steps of management involving nephrological, urological, cardiac, chest, vascular and anesthesia specialties.
Full cardiological assessment by laboratory as well as imaging investigations as required by cardiological team.
Pulmonary function tests should be accepted for the pulmonology team and anesthesia too.
Protocol management for COPD and avoiding exacerbations is valuable in such patient along with ruling out his need for oxygen therapy if needed.
Optimizing haemodialysis regarding the dry weight, avoiding interdialytic weight gain improves the chest condition mainly along with decreasing the risk of cardiac events.
Vaccinations according to transplant center prior to transplantation is advisable .
Induction by aggressive agents is mandatory to avoid the high risk of recurrence.
Protocol biopsy as scheduled by transplant centre post transplantation would be helpful.
Monitoring of complement levels, DSA titres (denovo) would be wise.
Smoking has a bad outcome on renal transplantation in many aspects, decreasing
graft survival by 30%, increasing mortality by elevating the risks of cerebrovascular as well as cardiac events leading to death with functioning graft. Also smoking is associated with a relative increased risk of invasive neoplasms especially lung neoplasms.
Smoking is considered more dangerous in renal transplant candidates who are already prone to multiple cardiac, infectious and allograft dysfunction events.
BERTRAM L. KASISKE and DAGMAR KLINGER
JASN April 2000, 11 (4) 753-759; DOI: https://doi.org/10.1681/ASN.V114753
your management of the pulmonary situation is fine.
two points in your immunology:
The donor is her brother and if she had C3 or DDD there is a genetic issue for alternative complement dysregulation which is a risk for the donor.
Eculizumab is not used for induction.
Ok ,Thanks for correction
I will try to read more in this topic
should stop smoking. Needs smoking cessation programme.
Smoking have negative impact on transplantation.
Thankyou for starting the contribution but notice that:
management means diagnosis and treatment so where do you start from here ; you need to evaluate her cardiovascular and respiratory system resrves to see if she is fit for both surgery and IS medications.
Try again and read your collegues answers to rient you more.