II. Relationship between early proteinuria and long-term outcome of kidney transplanted patients from different decades of donor age
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- 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 for your replies
The shortage of organs has pushed us to expand the donor pool.
Do you think that using ACE or ARBS has an impact on graft function and survival?
A RCT showed treatment with ramipril compared with placebo did not lead to a significant reduction in doubling of serum creatinine, ESRD, or death in kidney transplant recipients with proteinuria. These results do not support the use of ACEi with the goal of improving clinical outcomes in this population.
Knoll GA,Ramipril versus placebo in kidney transplant patients with proteinuria: a multicentre, double-blind, randomised controlled trial. Lancet Diabetes Endocrinol. 2016 Apr;4(4):318-26. doi: 10.1016/S2213-8587(15)00368-X. Epub 2015 Oct 23. PMID: 26608067.
Yes, Dr Hadeel. I note your viewpoint.
I quote one of our own from Liverpool:
Rustom R, Paraovan M, Sells RA, Jackson MJ, Hammad A, Bakran A, Brown M, Ahmad RA, Williams PS, Bell GM, Sharma AK, Bone JM. Effects of angiotensin-converting enzyme inhibitors (ACE-I) on progresion to end-stage renal failure in chronic vascular rejection (CR). Transplant Proceedings 2001;33:
No, it has no impact on graft or patient survival as shown by the study, because the pathogenesis of proteinuria is different than that of DM -nephropath or GN.
Yes, Dr Alshaikh. I note your viewpoint.
I quote one of our own from Liverpool:
Rustom R, Paraovan M, Sells RA, Jackson MJ, Hammad A, Bakran A, Brown M, Ahmad RA, Williams PS, Bell GM, Sharma AK, Bone JM. Effects of angiotensin-converting enzyme inhibitors (ACE-I) on progresion to end-stage renal failure in chronic vascular rejection (CR). Transplant Proceedings 2001;33:
Yes, Dr Benlomatayo. I note your viewpoint.
I quote one of our own from Liverpool:
Rustom R, Paraovan M, Sells RA, Jackson MJ, Hammad A, Bakran A, Brown M, Ahmad RA, Williams PS, Bell GM, Sharma AK, Bone JM. Effects of angiotensin-converting enzyme inhibitors (ACE-I) on progresion to end-stage renal failure in chronic vascular rejection (CR). Transplant Proceedings 2001;33:
Thank you prof for sharing this nice paper
-No evidence of benefit on the graft or patient survival. Clinicians should consider the benefits and risks of ACE inhibitors and ARBs before prescribing them to renal transplant recipients.
-Pooled analyses showed that the use of an ACE inhibitor and/or an ARB was associated with a greater decrease in glomerular filtration rate (GFR) than were control management strategies. use of an ACE inhibitor and/or an ARB was associated with a significantly greater decline in proteinuria than controlled strategies. but there was no difference in the degree to which the potassium level changed. Use of either drug was associated with a greater decline in hematocrit than controlled strategies.
-Hiremath S et al. (2007) Renin-angiotensin system blockade in kidney transplantation: a systematic review of the evidence. Am J Transplant 7: 2350–2360
Yes, Dr Weam. I note your viewpoint.
I quote one of our own from Liverpool:
Rustom R, Paraovan M, Sells RA, Jackson MJ, Hammad A, Bakran A, Brown M, Ahmad RA, Williams PS, Bell GM, Sharma AK, Bone JM. Effects of angiotensin-converting enzyme inhibitors (ACE-I) on progresion to end-stage renal failure in chronic vascular rejection (CR). Transplant Proceedings 2001;33:
and monitoring after initiation or increase in the dose 2-4 weeks
check up for (e GFR.serume K and serume creatinin leveles)
Yes, Dr Wadi. I note your viewpoint.
I quote one of our own from Liverpool:
Rustom R, Paraovan M, Sells RA, Jackson MJ, Hammad A, Bakran A, Brown M, Ahmad RA, Williams PS, Bell GM, Sharma AK, Bone JM. Effects of angiotensin-converting enzyme inhibitors (ACE-I) on progresion to end-stage renal failure in chronic vascular rejection (CR). Transplant Proceedings 2001;33:
Thanks you very much Prof.Sharma
some of the study showed that there is no role of ACE or ARBs in postrenal transplant out come but ithink we still need more study regarding this point
In a double-blind, placebo-controlled, randomised trial conducted in 14 centers in Canada and New Zealand, involving patients with eGFR of 20 and above, and proteinuria 0·2 g per day or greater, and randomly assigned them to receive either ramipril (5 mg orally twice daily) or placebo for up to 4 years, Treatment with ramipril compared with placebo did not lead to a significant reduction in doubling of serum creatinine, end-stage renal disease, or death in kidney transplant recipients with proteinuria. These results do not support the use of angiotensin-converting enzyme inhibitors with the goal of improving clinical outcomes in this population.
Reference:
Knoll GA, Fergusson D, Chasse M, Hebert P, Wells G, Tibbles LA, et al. Ramipril versus placebo in kidney transplant patients with proteinuria: a multicentre, double-blind, randomised controlled trial. Diabetes and Endocrinology. 2016 April; 4(4).
Many thanks Dr Huda.
I quote one of our own from Liverpool:
Rustom R, Paraovan M, Sells RA, Jackson MJ, Hammad A, Bakran A, Brown M, Ahmad RA, Williams PS, Bell GM, Sharma AK, Bone JM. Effects of angiotensin-converting enzyme inhibitors (ACE-I) on progresion to end-stage renal failure in chronic vascular rejection (CR). Transplant Proceedings 2001;33:
Thank you,
The impact of using ACE or ARBS on graft function and survival s till debatable
Pros
Cons
So it is recommended to start ACE/ARBS only if the following are met :
REFERANCES
1. Cross NB, Webster AC, Masson P, et al. Antihypertensive treatment for kidney transplant recipients. Cochrane Database Syst Rev 2009; :CD003598.
2. Curtis JJ, Laskow DA, Jones PA, et al. Captopril-induced fall in glomerular filtration rate in cyclosporine-treated hypertensive patients. J Am Soc Nephrol 1993; 3:1570.
3. Vlahakos DV, Canzanello VJ, Madaio MP, Madias NE. Enalapril-associated anemia in renal transplant recipients treated for hypertension. Am J Kidney Dis 1991; 17:199.
4. Gaston RS, Julian BA, Curtis JJ. Posttransplant erythrocytosis: an enigma revisited. Am J Kidney Dis 1994; 24:1.
That is a fantastic analysis, dear Dr Yusuf.
I quote one of our own from Liverpool:
Rustom R, Paraovan M, Sells RA, Jackson MJ, Hammad A, Bakran A, Brown M, Ahmad RA, Williams PS, Bell GM, Sharma AK, Bone JM. Effects of angiotensin-converting enzyme inhibitors (ACE-I) on progresion to end-stage renal failure in chronic vascular rejection (CR). Transplant Proceedings 2001;33:
Thank you, prof Ahmed
Both ACEI and ARBs are known Reno protective anti-proteinuria and anti-hypertensive agents however their role in the setting of renal transplant recipients is controversial and we need more studies to validate their effect
one study showed that treatment with ramipril compared with placebo did not lead to a significant reduction in doubling of serum creatinine, end-stage renal disease, or death in kidney transplant recipients with proteinuria. These results do not support the use of angiotensin-converting enzyme inhibitors with the goal of improving clinical outcomes in this population (1). While other evidence from meta-analysis and systematic review concluded that ACEI/ARB treatment may reduce patient death and graft loss (3)
another meta-analysis and RCT also address the short and long-term effects of ACEI, ARBS post-transplantation which concludes that after 12 months of use of ACEI, ARBS there was a reduction in GFR with lower HB levels and there were no significant differences in mortality between ACEI/ARB and non-ACEI/ARB groups (4).
I think such findings should not be generalized and we should individualize their use, for example, we preferred ACEI class for kidney transplant candidates with a background of IgA nephropathy as a primary disease also in recipients with a comorbid disease like CAD and DM , additional well-designed prospective studies are needed to confirm these findings.
References:
1. Knoll GA, Fergusson D, Chassé M, Hebert P, Wells G, Tibbles LA, Treleaven D, Holland D, White C, Muirhead N, Cantarovich M, Paquet M, Kiberd B, Gourishankar S, Shapiro J, Prasad R, Cole E, Pilmore H, Cronin V, Hogan D, Ramsay T, Gill J. Ramipril versus placebo in kidney transplant patients with proteinuria: a multicenter, double-blind, randomized controlled trial. Lancet Diabetes Endocrinol. 2016 Apr;4(4):318-26.
2. Webster AC, Cross NB. When evidence doesn’t generalize: the case of ACE inhibition. Lancet Diabetes Endocrinol. 2016 Apr;4(4):290-2
3.Jiang YM, Song TR, Qiu Y, Liu JP, Wang XD, Huang ZL, Lin T. Effect of renin-angiotensin system inhibitors on survival in kidney transplant recipients: A systematic review and meta-analysis. Kaohsiung J Med Sci. 2018 Jan;34(1):1-13
4. Liao RX, Lyu XF, Tang WJ, Gao K. Short- and long-term outcomes with renin-angiotensin-aldosterone inhibitors in renal transplant recipients: A meta-analysis of randomized controlled trials. Clin Transplant. 2017 Apr;31(4)
Thank you
There is no evidence fro graft survival. However, we stop the ACEI or ARB if the patient has been on it immediately post-transplant due to the risk of increase in serum creatinine and restart after stabilization of graft function
I don’t know what the thoughts and practices of my colleagues are?
Thank you
No, it has no impact on graft or patient survival as shown by the study, because the pathogenesis of proteinuria is different than that of DM -nephropath or GN.
Thank you
yes, I do use it routinely and have seen proteinuria does respond in over 50 % of my cohorts.
meta-analysis to evaluate the effects of ACEI/ARB treatment on patient and allograft survival after kidney transplant
articles from before May 2016, and we included 24 articles (9 randomised controlled trials [RCTs] and 15 cohort studies with 54,096 patients), in which patient or graft survival was compared between an ACEI/ARB treatment arm and a control arm
Pooled results showed that ACEI/ARB was associated with decreased risks of patient death (relative risk [RR] = 0.64; 95% confidence interval [CI]:0.49-0.84) and graft loss (RR = 0.59; 95%CI:0.47-0.74).
REFERENCE
https://pubmed.ncbi.nlm.nih.gov/29310811/
ACEI have good antiproteinuric effect specifically in glomerular proteinuria by modulating GFR. They have renoprotective effect especially if introduced when proteinuria has started and renal functions are still normal, I.e. early stages of glomerulopathies. hGood amount of data is available on that but ARBs have not gained similar popularity.
‘Now in reference to post transplant proteinuria, current data suggest that even ACEI has no effect but most studies include population when ACEI was started once proteinuria started. However, when high risk donors for post transplant proteinuria are selected (like old age) then what will be impact of starting ACEI prophylactically just after transplant even without proteinuria, has not been studied.
Since Patho genesis of post transplant proteinuria is different from diabetic, hypertensive and immune mediated glomerulopathies, a different study model is needed to confirm the role of ACEI
No.
Although ACE inhibitors/ ARBS have shown to reduce proteinuria, there is no effect on patient and graft survival (as seen in diabetic nephropathy).
References:
1) Ibrahim HN, Jackson S, Connaire J, Matas A, Ney A, Najafian B, West A, Lentsch N, Ericksen J, Bodner J, Kasiske B, Mauer M. Angiotensin II blockade in kidney transplant recipients. J Am Soc Nephrol. 2013 Feb;24(2):320-7. doi: 10.1681/ASN.2012080777. Epub 2013 Jan 10. PMID: 23308016; PMCID: PMC3559488.
2) Opelz G, Zeier M, Laux G, Morath C, Döhler B. No improvement of patient or graft survival in transplant recipients treated with angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers: a collaborative transplant study report. J Am Soc Nephrol. 2006 Nov;17(11):3257-62. doi: 10.1681/ASN.2006050543. Epub 2006 Oct 11. PMID: 17035607.
3) Seeman T, Feber J. Should ACE inhibitors or calcium channel blockers be used for post-transplant hypertension? Pediatr Nephrol. 2021 Mar;36(3):539-549. doi: 10.1007/s00467-020-04485-8. Epub 2020 Feb 14. PMID: 32060819.
4) Rustom R, Paraoan MT, Sells RA, Jackson MJ, Hammad A, Bakran A, Brown M, Ahmad RA, Williams PS, Bell GM, Sharma A, Bone JM. Effects of angiotensin-converting-enzyme inhibitors on progression to end-stage renal failure in chronic vascular rejection. Transplant Proc. 2001 Feb-Mar;33(1-2):1175-6. doi: 10.1016/s0041-1345(00)02449-0. PMID: 11267244.
In the this study it didn’t. Show benefit, but further large studies should be done to
confirms this result ,with their reno protective. effect in Proteinuric CKD patient in our
minds.
Summarize the study:
Aim:
Impact of different degrees of 1-year proteinuria on patient and graft survival in kidney transplants from different donor ages and evaluate its effect on recipient or donor risk and graft loss
Material & methods:
Retrospective observational cohort at Turin centre from January 2003 to December 2013 with 1127 consecutive kidney transplants.
They were divided into three groups:
group A (less than 50 years old) including 339 patients,
group B (50–69 years old) including 496 patients
group C (more than 70 years old, with maximum age of 88 years) including 292 patients.
Assuming 0.5 g/day as proteinuria cut-off, the association of 1-year PTO with DCGS and graft survival was present for all donor age classes
Any variation of proteinuria between 6 months and 1 year post-KT portends a worse graft out come when donor age was greater than 60 years
Conclusion:
Proteinuria(0.5 g/day) is always deleterious to transplant outcome even at early follow up time point and it should be closely monitored.
Its presence in the first year even in the absence of donor specific antibodies, patients should be evaluated for biopsy.
Level of evidence: III retrospective cohort study
Reflection on practice:
We at our centre always do 24 hours proteinuria evaluation in donors.
All our recipients regularly undergo 24 hours proteinuria, and if it is more than 500mg/day, then biopsy is performed
We monitor our donors by periodic urine ACR.
Do you think that using ACE or ARBS has an impact on graft function and survival
“This analysis neither supports nor refutes the hypothesis that RAS blockade improves clinical outcomes in kidney transplant recipients. A trial with more than 10,000 patients would be needed to definitively answer whether RAS blockade reduces transplant loss in this population.”
Hiremath S, Fergusson DA, Fergusson N, Bennett A, Knoll GA. Renin-Angiotensin System Blockade and Long-term Clinical Outcomes in Kidney Transplant Recipients: A Meta-analysis of Randomized Controlled Trials. Am J Kidney Dis. 2017 Jan;69(1):78-86.
“This meta-analysis demonstrated insignificant reduced risks of renal graft loss among renal transplant recipients who received RAS inhibitors“
Cheungpasitporn W, Thongprayoon C, Mao MA, Kittanamongkolchai W, Sathick IJ, Erickson SB. The Effect of Renin-angiotensin System Inhibitors on Kidney Allograft Survival: A Systematic Review and Meta-analysis. N Am J Med Sci. 2016 Jul;8(7):291-6.
“We therefore concluded that ACEI/ARB treatment may reduce patient death and graft loss, but additional well-designed prospective studies are needed to validate these findings.”
Jiang YM, Song TR, Qiu Y, Liu JP, Wang XD, Huang ZL, Lin T. Effect of renin-angiotensin system inhibitors on survival in kidney transplant recipients: A systematic review and meta-analysis. Kaohsiung J Med Sci. 2018 Jan;34(1):1-13.
The answer to the above question is very confusing. I have quoted three systemic reviews and meta-analysis, with the latest one saying that it may reduce patient death and graft loss, although the subset analysis in this meta-analysis showed that there is benefit seen in cohort studies and no benefit seen in RCTs.
The mentors may help us answer this.
Proteinuria deserve to be treated with ACEi or an ARB, as proteinuria increases CVD risk and mortality. If it was used with stable creatinine, I think it will not harm.
Ø study investigated the impact of post-transplant proteinuria in the first year in 1127 kidney transplants analysing the impact of different donor ages.
Ø Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age groups.
Ø In addition, 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old (p < 0.05; Odd Ratio 1.8).
Ø 1-year graft function (eGFR < or ≥ 44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure (Hazard Ratio 2.77 vs Hazard Ratio 2.46).
Ø Low-grade proteinuria (0.2–0.5 g/day) demonstrated a trend for worse graft survival with increasing donor age. Also in kidney-paired analysis proteinuria ≥0.5 effect was more significant with donors > 50 years old (Odd Ratio 2.3).
Ø Post-transplant proteinuria was increasingly harmful with older donor age. Proteinuria ≥0.5 g/day correlates with worse outcomes in all transplanted patients. Prognostic value of proteinuria and eGFR for graft and patient survival was comparable and these two variables remain significant risk factors even in a multivariate model that take into consideration the most important clinical variables (donor age, rejection, delayed graft function and cytomegalovirus viremia among others)
evidence suggesting a benefit for ACEi/ ARB use in transplant recipients is still lacking. They showed that the use of these agents was often associated with a significant reduction in proteinuria and eGFR
Level 3
Please reflect on the guidelines and refer to your practice.
Follow-up of proteinuria post-transplant every 3 month
This retrospective observational cohort study’s primary aim is to analyze the effect on patient and graft survival in kidney transplant from different donor ages of varying degrees of one year proteinuria .Secondary aim are to to evaluate the correlation between proteinuria and donor or recipient risk factors with graft loss. Inclusion criteria included 1127 kidney transplants with all deceased donor grafts from January 2003 to December 2013 and follow up period of 10 years duration. Pre-transplant donor biopsies were performed on the basis of a multidimensional assessment including macroscopic appearance, renal function, donor comorbidities and echographic characteristics.Post-transplant renal biopsies were performed for cause (mainly when serum Creatinine increased ≥20% of baseline value or with proteinuria > of 0.5–1 g/day). All recipients received basiliximab induction or ATG (if high immunological risk) followed by triple maintenance therapy (steroids, CNI and MMF or AZA).
RESULTS:
Proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age groups. The donor age was associated with higher risk of post transplant proteinuria.The 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old . One year post transplant proteinuria was associated with NODAT, glomerulonephritis and rejection. Low grade proteinuria (0.2 – 0.5 gm/day) was not associated with a significant reduction in graft and patient .RAS blockers helps in reducing proteinuria but no impact on graft survival.
Level of evidence: retrospective cohort study(level II)
Reflection on guidelines and our local practice
Deceased donor program not in our country. For living donation, we monitor post-transplant proteinuria closely with UPCR done at one week ,then at one month , three months, six months and one year.Patient counseled in detail about risk of proteinuria and reduced graft function post transplantation if donor is elderly.
This is a retrospective observation cohort study with level 3 evidence to study the impact of post transplant proteinuria among kidney transplant recipients. A total of 1127 kidney recipients were recruited at Turin University Renal Transplant Center between January 2003 and December 2013.Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age groups. In addition, 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old (p < 0.05; Odd Ratio 1.8). 1-year graft function (eGFR < or ≥ 44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure (Hazard Ratio 2.77 vs Hazard Ratio 2.46). Low-grade proteinuria (0.2–0.5 g/day) demonstrated a trend for worse graft survival with increasing donor age. Also in kidney-paired analysis proteinuria ≥0.5 effect was more significant with donors > 50 years old (Odd Ratio 2.3). Strenghts of the study are related to homogeneity of the population, characterized by a wide range of data coming from over a thousand of KTs performed with the same team of surgeons, nephrologists and pathologists. Patients were centrally followed in the long term with all data recorded in patients’ charts. The limitation include the absence of protocol graft biopsies for center policy and no routinely donor specific antibody evaluation in the first year. In conclusion, post-transplant proteinuria was increasingly harmful with older donor age. Proteinuria ≥0.5 g/day correlates with worse outcomes in all transplanted patients
It is a retrospective observational cohort study (level 3 evidence),it includes 1127 patients with deceased kidney donor,the study concern about the impact of proteinuria of more than 0.5g/24hr in patients and graft survival
the result show it had negative impact and the use of ACEI and ARBS to reduce it amount found to be effective
This retrospective observational cohort study was to analyse the impact of different degrees of 1-year proteinuria on patient and graft survival in kidney transplants from different donor ages and evaluate the correlation between proteinuria and donor or recipient risk factors with graft loss.
Secondary outcome was to evaluate proteinuria as risk factor for kidney graft survival in multimodal models considering renal function and other main clinical variables.
Patients were grouped into group A (< 50 years), group B (50–69 years), group C ≥ 70 years.
The outcomes were analysed for patients with at least 1 year of follow-up according to 1-year post-KT extent. confounding factors elimination was done by mainly explored proteinuria values after the sixth post-KT month; when comparing 6-month and 1-year proteinuria (1-year PTO), the latter showed a better correlation with death censored graft survival (DCGS) with an AUC 0.64 vs 0.59
The study demonstrated that occurrence of proteinuria, (≥ 0.5 g/day), at the first post-transplant year, was significantly associated with graft and patient survival.
Proteinuria between 0.2 and 0.5 g/ day was not related to adverse outcome. However, study demonstrated an association (a trend, not reaching significance) between DCGS and low-grade PTO (≥ 0.2 < 0.5 g/day) only in kidneys from donors older than 70 years old.
Predisposition to proteinuria development in the study population appeared to be certainly related to both donor and recipient characteristics (donor age, pretransplant diabetes, glomerular Karpinsky score) but, as it is demonstrated by paired kidney analysis, early post- KT events (acute rejection, CMV infections, new onset diabetes after transplantation and urological complications such as ureteral stenosis) contribute to determine kidney fate and prognosis.
CMV viraemia post-transplant resulted as an independent predictor of DCGS in Cox multivariate analysis (HR 2.1).
As for rejection, when we consider rejection as an event in the entire follow-up, its role is comparable to the one of the other main risk factors (HR respectively 2.5 vs 2.1 and 2.4).
Strengths
homogeneity of the population, characterized by a wide range of data coming from over a thousand of KTs performed with the same team of surgeons, nephrologists and pathologists.
Patients were centrally followed in the long term with all data recorded in patients’ charts.
Validation of prognostic impact of proteinuria in a subset of paired kidneys, thus limiting undetermined donor-derived confounding factors
Limitations :
absence of routinely donor specific antibody evaluation in the first year, which was available only in a minority of patients, so that we did not evaluate our population under this aspect;
lack of qualitative differentiation of urinary protein, considering that tubular or glomerular proteinuria could have different impact on graft outcome, as underlined in previous studies
Conclusion
The presence of proteinuria in the first year at a relatively low extent (0.5 g/day), even in the absence of donor specific antibodies, should suggest a careful evaluation of patients leading to for-cause biopsy. Utility of protocol biopsy in patients with nonstandard donor, even in the absence of risk factors, should be ascertained by further studies.
What is the level of evidence provided by this article?
level III
INTRODUCTION :
Proteinuria is known to be an independent risk factor for cardiovascular disease and mortality in native kidneys as well as an indicator of renal damage and a predictor of allograft loss after kidney transplantation.
METHODS
Reterospective observational cohort study which included all deceased donor grafts.
‘Study period was from Jan 2003 to Dec 2013.
Immunosuppressive regimen differed according to different transplantation eras and different populations. The most adopted schedules were: induction with steroid boluses, rapidly tapered to 20mg/day of oral prednisone and two doses of anti-CD25 antibody. Subjects at high immunological risk (e.g. previous transplant lost for acute rejection, high PRA titer) were treated with antithymocyte globulin. Maintenance therapy was generally based initially on a triple-drug protocol. Calcineurin in- hibitor (CNI), either tacrolimus or Cyclosporine, was associated to Mofetil Micofenolate/Micophenolic Acid or Azathioprine and prednisone.
Patients were divided in 3 groups according to donor age: group A (< 50 years), group B (50–69 years), group C ≥ 70 years.. The outcomes were analyzed for patients with at least 1year of follow-up according to 1-year post-KT extent.
‘At one year post transplant outcome, proteinuria was defined as 0.5 GM/day with low grade proteinuria being 0.2gm/day to 0.5gm/day.
Main outcomes were death censores graft survival and patient survival.
RESULTS
Donor age increase the risk of proteinuria – older tend to has more proteinuria.
CONCLUSION :
This study clearly states that proteinuria is always deleterious to transplant outcome even at early follow up time point. The need of close monitoring of proteinuria should be repeatedly performed especially in cases of elder kidney donations.
The level of evidence is III.
Please reflect on the guidelines and refer to your practice.
In our transplantation center practice we not accept older donors specially those more than 60 years of age, we use to follow urinary protein by spot urine for protein/creatinine ratio test, as it is an isolated factor for graft loss, disease recurrence, occurrence of NODAT….
This is a retrospective observational cohort study of 1127 deceased donor grafts performed at Turin University Renal Transplant Center “A. Vercellone” from January 2003 to December 2013.
This aim was to investigate the impact of post transplant proteinuria in the first year. Transplants with proteinuria >0.5g/day correlated with poor graft and patient outcome in all donor age groups. In addition, 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors >60years old. 1-year graft function (eGFR < or≥44ml/min) had similar impact to proteinuria (≥ 0.5g/day) on graft failure. Low-grade proteinuria (0.2–0.5g/day) demonstrated a trend for worse graft survival with increasing donor age. Also in kidney-paired analysis proteinuria ≥0.5 effect was more significant with donors >50years old.
Strength
1- homogeneity of the population, characterized by a wide range of data coming from over a thousand of KTs performed with the same team of surgeons, nephrologists and pathologists. Patients were centrally followed in the long term with all data recorded in patients’ charts.
2- is the validation of prognostic impact of proteinuria in a subset of paired kidneys, thus limiting undetermined donor-derived confounding factors
Limitation
1- absence of protocol graft biopsies for center policy;
2- absence of routinely donor specific antibody evaluation in the first year, which was available only in a minority of patients
3- lack of qualitative differentiation of urinary protein, considering that tubular or glomerular proteinuria could have different impact on graft outcome, as underlined in previous studies
level of evidence is II
we usually avoid donors with proteinuria more than 150 mg ?day. if they develop proteinuria we give RAS blockers.
Proteinuria of renal transplant recipient has poor graft and patient survival and higher risk for CV disease especially if occur within the first year following transplantation
Risk factors for post-transplant proteinuria includes older donor age, DGF, higher HLA mismatches and high BMI
CMV infection, rejection, vascular and urological complications were more common in transplant recipients with older age in donors, but NODAT and glomerulonephritis were not influenced by donor age
ECD eg: elderly is used to expand the donor pool , and was found to be associated with higher incidence of DGF which is it is lower when matching the donor with the recipient age ( old for old strategy )
This is a retrospective cohort study with level III of evidence evaluating 1127 deceased kidney transplants recipients regarding the impact of proteinuria (> 0.5 g/d) occurring in the first year following transplantation on graft and patient outcome and its relation to the donor age.
Results:
Reduction of proteinuria but with no effect on graft or patient survival was associated with use of ARBS or ACEI.
Summary:
Proteinuria 0.5 gm or more following transplantation is associated with poor graft and patient outcomes with is more significant in older donor age.
Reflection:
Please summarize this article in your own words
The aim of this study includes the following:
1- assess the effect of different levels of one-year proteinuria on renal graft and kidney transplant recipient’s survival compared to different donor ages.
2- Assess the relation of graft loss between proteinuria and different risk factors from donor and recipient.
3- Assess proteinuria as a risk factor for renal graft survival considering renal function and other clinical variables.
Methods:
Type of the study: Retrospective observational.
Study center: Turin University Renal Transplant Center.
Timing: January 2003-January 2013.
Study population: 1127 Deceased Donor graft recipients.
Exclusion: multi-organ transplantation and those with follow up less than 6 months.
Data collected: patients demographics, comorbidities, e-GFR by CKD-EPI, and 24h urine protein at time of discharge, then 3monthly then at 1,2,5 years post-transplant.
US abdomen, IS therapy and post-transplant biopsy were included as well.
Patients classifications: into 3 groups
Group A: 339 patients aged below 50 years.
Group B: 496 patients aged 50-69 years.
Group C: 292 patients aged 70-88 years.
Follow up: median was 8.2 years.
Outcomes:
Death censored graft survival (DCGS) and patient survival.
Results:
· Age of donors increased the degree of proteinuria.
· DCGS for patients aged 70 years or above was 29.7% vs 72.3% in younger recipients with same level of proteinuria.
· The most relevant clinical variables for DCGS include the following: 1-year proteinuria more than 0.5 gm/day, donor age, recipient age, low e-GFR, DGF, Rejection, 1-year CMV infection.
· 1-year proteinuria >0.5 gm/day was associated with NODAT, GN and rejection.
· Proteinuria was found in association with CMV viremia, and transplant urological complications.
Strengths:
Large study population
Homogenous demographic data.
Prognostic impact of proteinuria in paired kidneys was validated
Limitations:
1- Retrospective.
2- Single center.
3- No protocol biopsy.
4- No DSA monitoring.
5- No urinary protein qualitative differentiation.
What is the level of evidence provided by this article?
Level III, retrospective observational study.
Introduction:
Proteinuria is considered a significant independent risk factor for development of cardiovascular disease and mortality in native kidneys besides being an important indicator of renal damage and a predictor of impending allograft loss post renal transplantation.
Previous studies recommended assessment of proteinuria post renal transplantation should be done 3 months extending up to one year.
A strong correlation of 1- and 3-month proteinuria (per every 0.1 g/day increase) with graft loss was discovered by Halimi and his coworkers. Other study conducted by Amer and his colleagues analyzed the first year post renal transplant proteinuria revealed Hazard Ratio (HR) for graft loss of 2.15 (CI 95% 0.68–6.8), associated with proteinuria between 150 and 500 mg/day and an HR of 5.11 (CI 95% 1.4–19.2) with higher level of proteinuria.
A recent study performed by Naesens et al. highlighted a significant direct correlation between 1-year post renal transplant proteinuria and graft loss totally non attributed to graft histology, but only for proteinuria with values higher than 1 g/day (HR 2.17). While Cantarovich and coworkers observed that proteinuria > 0.5 g/d, at 3-month and 2-year post-KT was a significant prognostic marker of graft outcome but the 5-years proteinuria significance was not.
Only one study was concerned with impact of proteinuria on transplants derived from Extended Criteria Donors, unfortunately it had a relatively small sample size and without comparison to standard donors.
The target of this project was to analyze the impact of different grades of 1-year proteinuria on both patient and graft survival in renal transplants from different donor ages. Evaluation of the correlation between proteinuria and donor age or recipient risk factors with graft loss was also addressed among the targets. Identifying proteinuria as risk factor for renal graft survival including renal function and other main clinical variables is searched.
Methods
A retrospective observational cohort study design involving all deceased donor grafts carried out at Turin University Renal Transplant Center “A. Vercellone” from January 2003 to December 2013.
Multiorgan grafts were excluded from analysis, with only remaining 1127 consecutive kidney transplants (KT).
Data were collected from patients’ individual charts: creatinine and proteinuria (in 24-h urine collections) were evaluated before discharge, at 3, 6 months and at 1, 2 and 5 years post transplantation. Renal allograft function (eGFR) was estimated via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
Pre-transplant donor biopsies were also available. Taking in account that majority of cases biopsy is performed for donors older than 70 years. Criteria as donor cerebrovascular cause of death in the absence of vascular malformation, imaging parameters (renal cortical thickness, renal longitudinal diameter, and longitudinal diameter discrepancy between both kidneys), donor hypertension, donor diabetes, donor active smoking, and donor proteinuria > 100 mg/dl at urinalysis are highly important.
Post-transplant renal biopsies were done for cause as when serum Creatinine increased ≥20% of baseline value or with proteinuria > of 0.5–1 g/day. Karpinsky score was used to define suitability for single or dual KT or refusal of organs.
Classification of patients was into 3 groups based on the donor age: group A (< 50 years), group B (50–69 years) and group C ≥ 70 years.
Proteinuria better correlated to death censored graft survival DCGS at 6 month and 1 year with AUC 0.64 vs 0.59 respectively. Low-grade proteinuria ranged between 0.2 g/day and 0.5 g/day. The best correlation with is the eGFR value at 1-year post-KT.
Chief outcomes were death censored graft survival (DCGS) and patient survival. Paired kidney analysis was considered only in cases where both kidneys from the same deceased donor were transplanted at our institution (370 recipients, 185 pairs).
Results
The impact of proteinuria on patient survival was well observed in younger donors. Donor age was associated with the increased magnitude of proteinuria impact: DCGS of patients with donor age ≥ 70 years and higher 1-year proteinuria was only 29.7% compared to 72.3% in recipients of kidneys from younger donors with the same proteinuria (p = 0.03).
Low grade proteinuria group analysis revealed no association of significance of 1-year PTO with patient and graft survival and DCGS at any donor age. However, donors ≥70 years, regarding graft and DCGS (DCGS 82.3% with 1-year proteinuria < 0.2 g/day vs 65.3% with 1-year proteinuria 0.2–0.5 g/day; p = 0.09).
The total Karpinsky score as well as glomerulosclerosis score were not associated with DCGS differences.
Patients with increase in 6mo-1 yr proteinuria higher than 0.1 g/day had lower DCGS irrespectively of donor age when compared to those with lower increase (10-year graft survival 69.9% vs 90.2%; p < 0.01).
Proteinuria impact (≥0.5 g/day) was not linked to evident variation in DCGS in the different age classes.
Adverse events by 1-year post-KT proteinuria > 0.5 g/day occurred as development of new onset diabetes (NODAT), glomerulonephritis and rejection. Transplant urologic complications and Cytomegalovirus (CMV) viremia had clear relation to proteinuria.
Correlation between proteinuria and creatinine impact on graft survival, 1-year eGFR was markedly linked to patient, graft and DCGS (91.2% with eGFR ≥44 ml/min while 65.2% with eGFR < 44 ml/min; p < 0.01).
Predictors of DCGS were primarily the following: 1-year proteinuria, donor age, recipient age, eGFR, DGF, rejection, 1-year CMV infection.
Among 185 paired renal donations, 43 couples with 1-year proteinuria discrepancy (one graft with 1-year proteinuria ≥0.5 g/day and the paired one with proteinuria < 0.5 g/day) revealed the fact that DCGS was respectively 86.6% for recipients with proteinuria < 0.5 g/day and 51.9% for the twin kidney with proteinuria > 0.5 g/day; p < 0.01. This was highly elaborated in donor age ≥ 70 years affecting DCGS, while not in donor age less than 50 yr.
Discussion
Higher levels of albuminuria in general population is associated with increased mortality as well as progression to end-stage renal disease. Also several studies in known diabetics and nondiabetic renal disease patients highlighted the fact that the presence of severe albuminuria significantly accelerated the rate of CKD progression.
Studies recommending allograft biopsy performance on new onset proteinuria or unexplained proteinuria 3.0 g/mg creatinine or 3.0 g/24 h occurrence are of extremely low level of evidence.
The potential risk of development of proteinuria at early period post-renal transplantation in the first year must be regarded as a key risk factor for post-transplant prognosis.
Development of proteinuria, (≥0.5 g/day), at the first post-transplant year, was related to graft survival and patient survival according to this study.
This is considered the first study to assess the impact of development of proteinuria on KTs from variable donor age classes, illustrating a synergic effect of proteinuria ≥0.5 g/day and donor age ≥ 70 years on DCGS. The explanation was reasonable as older donor kidneys were more sensitive to proteinuric injuries opposite to younger ones with very evident differences of DCGS in different donor age classes having similar level of proteinuria. This again points to the fact that variation of proteinuria between 6 months and 1 year post-KT carries a worse graft prognosis when donor age was ≥60 years.
Reduced capacity of renal autoregulation is apparent in aging kidneys. Thus kidneys derived from elderly donors, which are even more susceptible to various types of injuries lack compensatory hyperfiltration of glomeruli in cases of reperfusion injury, or rejection or drug toxicity for instance.
The expected overall infections and CMV viremia in addition to vascular and urological complications were estimated to be frequently higher in older donor population, increasing the susceptibility to progress to early post-transplant proteinuria.
That is why some studies recommend decreasing immunosuppressive therapy in case of infection and of the lower quality of older donor tissues in comparison to the younger donor kidneys. This was associated with imbalance between infection and rejection rates, especially when donor age exceeded 50 years.
As stated by this study, 1-year proteinuria ≥0.5 g/day (HR 2.77) is comparable to CKD-EPI < 44 ml/min (HR 2.46) in predicting graft failure. So when donor age exceeds 70 years, the association of cardiovascular diseases and mortality becomes even worse.
This study was concerned by identifying the possible link among proteinuria, donor age and subsequent higher proteinuria-mediated damage in older donors. This study also confirmed the role of MTORi in inducing proteinuria via targeting glomerular podocytes.
Accordingly, patients used mTORi maintenance therapy in the first year (16%) were excluded from this study.
Strenghts of the study:
Homogeneity of the population.
Wide range of data obtained from over a thousand of KTs performed by the same team of surgeons, nephrologists and pathologists.
Optimum follow up of the patients for long term duration with all data recorded in patients’ charts.
Validation of the prognostic impact of proteinuria in cases of paired renal donations, thus limiting undetermined donor-derived confounding factors.
Limitation of this study:
Absence of protocol graft biopsies.
Absence of routinely donor specific antibody evaluation in the first year.
Lack of qualitative differentiation of urinary protein either tubular or glomerular of origin.
Conclusions:
This study clearly states that proteinuria is always deleterious to transplant outcome even at early follow up time point. The need of close monitoring of proteinuria should be repeatedly performed especially in cases of elder kidney donations.
The level of evidence is III.
According to our centre, no donations are accepted exceeding 60 years of age by the law of our country. No paired renal donations, as cadaveric donation is not performed in EGYPT till now. However proteinuria post renal transplantation is a worse predictor factor in our practice.
Introduction:
Proteinuria is an independent risk factor for CV disease and mortality in native kidneys as well as an indicator of renal damage and a predictor of allograft loss after kidney transplantation.
Aim of the study:
Study design
A retrospective observational cohort study of all deceased donor grafts done at one center from January 2003 to December 2013.
The selected population were classified by donor age:
group A (less than 50years old)
group B (50–69years old)
group C (more than 70 years old, maximum age is 88years)
The impact of proteinuria on kidney transplantation from different donor age classes was analyzed, The results showed a synergic effect of proteinuria ≥0.5 g/day and donor age ≥ 70 years on deaths censored graft survival (DCGS) .
Older donor kidneys were more sensitive to proteinuria injuries when compared with younger ones (worse graft outcome when donor age was ≥60years). There was an association between DCGS and low-grade proteinuria (≥ 0.2 < 0.5 g/day) in kidneys donors > 70 years old . The early post-transplant events like acute rejection, new onset diabetes after transplantation, CMV infections, and urological complications such as ureteral stenosis were important determinants of the kidney fate and prognosis .
conclusion :
Proteinuria equal to or more than 0.5 g/day is always deleterious to transplant outcome including patient and graft survivals, even at early follow up time point while low grade proteinuria of 0.2-0.5 g/day showed worse graft survival with increasing donor age.
6 M to 1 year post-transplant proteinuria was significantly associated with poor graft outcome especially if donors were ≥60. Accordingly, the close monitoring of proteinuria is important in elderly donors.
What is the level of evidence provided by this article?
Level of evidence: observational retrospective cohort study level 3.
Reflect on the guidelines and refer to your practice?
We don’t proceed in the transplant process when the donor is found to be with significant proteinuria.
Checking for proteinuria is important in the early post –transplantation period then at least yearly thereafter. New onset proteinuria > 1 gm is an indication for renal biopsy.
Recipients with older age donor should be monitored intensively.
The use of ACE, ARBS to reduce proteinuria is well known, However, they have no effect on the patient and graft survival in this group entity.
This study was done to investigate the early proteinuria in transplanted kidney, the cut off was set at 0.5gm/D and its correlation with with graft out come, loss of function in all donors. it was found that early (6m-1 year proteinuria signifies graft outcomes. Also when the age was >50 the worsted out come.
literature do not support use of ACEi/ARBs in these pateints.
Proteinuria is an independent risk factor for cardiovascular disease and mortality in native kidneys as well as an indicator of renal damage and a predictor of allograft loss.
optimal timing for measuring proteinuria is between 3 months and one year post-KT.
Number of studies showed a strong correlation of 1-and 3-month proteinuria (per every 0.1 g/day increase) with graft loss
In a recent study Naesens et al. found a strong direct correlation between 1-year post KT proteinuria and graft loss for proteinuria values higher than 1 g/day .
In the study by Cantarovich and coworkers, proteinuria > 0.5 g/ d, at 3-month and 2-year post-KT was a significant prognostic marker of graft outcome. At 5-years, this significance was not observed
Aim of this study was to analyze the impact of different degrees of 1-year proteinuria on patient and graft survival with different donor ages.
▪︎Methods
retrospective observational cohort study of deceased donor grafts performed at Turin University Renal Transplant Center from 2003 to December 2013.
Data collected includes: creatinine and proteinuria (in 24-h urine collections) at discharge, at 3, 6 months and at 1, 2 and 5 years after transplantation,eGFR was estimated by CKD-EPI.
Patients were divided in 3 groups according to donor age: group A (< 50 years), group B (50–69 years), group C ≥ 70 years.
▪︎Results
Assuming 0.5 g/day as proteinuria cut-off;
– association of 1-year PTO with DCGS and graft survival was present for all donor ages.
-Donor age increased the magnitude of pro-teinuria impact.
-low grade proteinuria group analysis did not show any significant association of 1-year PTO with patient and graft survival and DCGS at any donor age.
-higher glomerulosclerosis score showed a good correlation with a higher 1-year proteinuria.
-total Karpinsky score as well as glomerulo-sclerosis score were not associated with DCGS differences.
-increase of proteinuria was associated with poor graft survival and DCGS.
– Patients with increase in 6mo-1 yr proteinuria higher than 0.1 g/day had lower DCGS if compared with patients with lower increase.
-1-year post-KT proteinuria > 0.5 g/day was associated with new onset diabetes (NODAT), glomerulonephritis and rejection. Notably, also transplant urologic complications and Cytomegalovirus (CMV) viremia had an association with proteinuria.
-Angiotensin Converting Enzyme inhibitors/ Angiotensin II Receptor Blockers therapy didn’t affec proteinuria .
-Proteinuria was associated with raising creatinine level and decrease eGFR.
older donor.
▪︎discussion
The study demonstrated that occurrence of proteinuria,(≥ 0.5 g/day), at the first post-transplant year, was significantly linked to graft survival and patient survival in the whole population under study.
And there was a synergic effect of proteinuria ≥0.5 g/day and donor age ≥ 70 years on DCGS.
Very low grade proteinuria (between 0.2 and 0.5 g/ day) was not related to outcome, although there was association between DCGS and low-grade PTO from donors older than 70 years old.
Predisposition to proteinuria development was related to both donor and recipient characteristics (donor age, pre-transplant diabetes, glomerular Karpinsky score).
But early post-KT events (acute rejection, CMV infections, new onset diabetes after transplantation and urological complications contribute to determine kidney fate and prognosis.
▪︎Strenghts of the study
-homogeneity of the population.
-wide range of data coming from over a thousand of KTs.
–performed with the same team of surgeons ,nephrologists and pathologists.
-followe up for long term.
– validation of prognostic impact of proteinuria in a subset of paired kidneys.
▪︎ limitation of this study
-absence of protocol graft biopsies.
– absence of routinely donor specific antibody evaluation in the first year,
– lack of qualitative differentiation of urinary protein
▪︎Conclusions
proteinuria is always deleterious to transplant outcome even at early follow up time point.
presence of proteinuria in the first year at a relatively low extent (0.5 g/day), even in the absence of donor specific antibodies, should suggest a careful evaluation of patients leading to for-cause biopsy.
Utility of protocol biopsy in patients with nonstandard donor, even in the absence of risk factors, should be ascertained by further studies
· Proteinuria is independent risk factor for cardiovascular disease and mortality in native kidneys and an indicator of renal damage and a predictor of allograft loss after kidney transplantation
· Aim of this study was to detect the effect of 1-year proteinuria on patient and graft survival in kidney transplants from different donor ages and to evaluate the correlation between proteinuria and donor or recipient risk factors with graft loss
· Secondary aim: evaluation of proteinuria as a risk factor for kidney graft survival in multimodal models taking into account renal function and other main clinical variables
Methods
· This is a retrospective observational cohort study including all deceased donor grafts performed at Turin University Renal Transplant Center “A. Vercellone” from January 2003 to December 2013
· 1127 consecutive kidney transplants were included, with exclusion of multiorgan grafts
· Immunosuppressive induction with: steroid boluses, rapidly tapered to 20 mg/day of oral prednisone and two doses of anti-CD25 antibody (Simulect), but high immunological risk patients given antithymocyte globulin (Thymoglobuline)
· Maintenance therapy: a triple-drug protocol. CNI (tacrolimus or Cyclosporine)+MMF/MFA or Azathioprine + prednisone.
· Data were collected from patients’ individual charts
· (eGFR) was estimated by (CKD-EPI) equation
· Pre-transplant donor biopsies were not performed in donors < 50 years and always performed in donors older than 70 years
· Post-transplant renal biopsies were performed for increased serum Creatinine in or for proteinuria > of 0.5–1 g/day
· Patients were divided in 3 groups according to donor age: group A (< 50 years), group B (50–69 years), group C ≥ 70 years
Results
· the impact of proteinuria on patient survival was noted only for younger donors
· 6mo-1 yr proteinuria increase was not associated with patient survival at any donor age, while any increase of proteinuria between these time points was associated with poor graft survival and DCGS
· ACEi/ARB therapy did not influence 6mo-1 yr proteinuria variations
· 1-year post-KT proteinuria > 0.5 g/day was associated with new onset diabetes (NODAT), glomerulonephritis and rejection
· transplant urologic complications and CMV viremia also associated with proteinuria
Discussion
· For the general population, the risk of adverse outcomes (mortality, progression to ESKD) increases with higher levels of albuminuria
· Many studies in diabetic and nondiabetic renal disease patients, confirm that marked albuminuria (> 300 mg/day) is associated with a faster rate of CKD progression
· This study demonstrated that occurrence of proteinuria,(≥ 0.5 g/day), at the first post-transplant year, was significantly linked to graft survival and patient survival in the whole population under study
· Very low grade proteinuria (between 0.2 and 0.5 g/ day) was not related to outcome, but there an association between DCGS and low-grade PTO only in kidneys from donors> 70 years old
· There are a strong correlation between overall infection and rejection rates, especially when donor age was > 50 years
Strengths of the study :
· homogeneous population, with a wide range of data coming from over a thousand of KTs performed with the same team of surgeons, nephrologists and pathologists.
· Patients were centrally followed in the long term with all data recorded in patients’ charts.
· The validation of prognostic impact of proteinuria in a subset of paired kidneys, thus limiting undetermined donor-derived confounding factors
limitation of this study:
· absence of protocol graft biopsies for center policy
· absence of routinely DSA evaluation in the first year, except in a minority of patients
Conclusions
· The authors suggest that, in the context of elderly donors and in the absence of acknowledged effective pharmacological tools, when other causes of proteinuria are excluded, close monitoring of proteinuria should be repeatedly performed
· Dealing with immunologic “low-risk” patients, the presence of proteinuria in the first year at a relatively low extent (0.5 g/day), even in the absence of DSA, should suggest a careful evaluation of patients leading to for-cause biopsy
What is the level of evidence provided by this article?
A retrospective observational cohort study, evidence 3
Please reflect on the guidelines and refer to your practice.
We usually do urine analysis monthly. If protein detected in dipstick, 24 h urine protein requested and further investigations. Usually I try with ACEi or an ARB
1. Please summarise this article in your own words
Background
Trying to increase donors pool led to use of elderly donors with older kidneys. Since these kidneys have reduced reserve, they are usually allocated to age matching recipients. Early proteinuria has been associated with more cardiovascular disease and graft loss. Best time for measuring proteinuria was found to be 3-12months post-transplant. The impact of this proteinuria on long term patient graft survival is not well studied.
Methods
This is a retrospective study, involving all donor done between January 2003 to December 2013 in Turin University Renal Transplant Center. Multiorgan transplant were excluded, analysis included remaining 1127 consecutive kidney transplant.
Results
1127 distributed in 3 groups based on their age:
1. <50 years group 1
2. 50-69 years group 2
3. 70 or more, group 3
Mean follow up 8.3years.
Cut of for proteinuria was 0.5gm/day.
Impact of proteinuria on patient survival noticed only in young donors. Donor age increased the magnitude of proteinuria impact: DCGS of patients with donor age ≥ 70 years and higher 1-year proteinuria was only 29.7% versus 72.3% in recipients of kidneys from younger donors with the same proteinuria (p = 0.03). For those who have biopsies, higher glomerulosclerosis was found significantly associated with one year proteinuria.
Proteinuria at 6months to 1year was no associated with one year patient survival but with graft survival specially with older donors.
Treatment with ACE/ARB did not influence proteinuria.
One year post transplant proteinuria was associated with NODA, glomerulosclerosis, rejection CMV and more need for biopsies.
One year e GFR >44ml/min was strongly associated with graft and patient survival 92% versus 65%,
What is the level of evidence provided by this article?
Level 111.
2. Please reflect on the guidelines and refer to your practice.
Age matching of donors.
Monitoring proteinuria 6-1year post transplant. Doing kidney biopsy if significant, new or recurrent GN is suspected. Using ACEI/ARB or nondihydropyridine Calcium channel blockers if proteinuria with hypertension despite no strong evidence for their use in transplant patients.
INTRODUCTION:
Studying the potential association between kidney stones and future development of
chronic kidney disease is quite complicated as many people with kidney stones have
multiple comorbid conditions.
Kidney donors, This Elvive study compare risk for donors with renal stone to develop
ESRd, proteinuria and hypertension.
Previous studies showed increase risk of CKD in donors with renal stones
pretransplantion, (Canadian study and NHNES).ARC shows no risk.
MATERIALS AND METHOD:
The Renal and Lung Living Donor Evaluation Study (RELIVE),
There were 8922 live kidney donations at the study sites from 1963 to 2007.
Baseline demographic and laboratory measurements at donation were abstracted from
centers records. Family history of hypertension, diabetes mellitus (DM), kidney disease,
stroke, or heart disease in donors’ first-degree relatives were recorded.
A history and timing of kidney stones was obtained from medical record abstraction,
imaging studies and by donor self, center records.
Post-donation follows up of hypertension, cardiovascular disease (CVD), ESKD,
Proteinuria. Results in theses posttransplant domain were compared between. Donors
and matched controls.
The donor selection process was highly comparable between centers. three centers did
preferentially take the kidney with a stone in cases of unilateral stones.
Methods Study design:
a retrospective observational cohort study.
all deceased donor grafts performed at Turin University Renal Transplant Center.
Time Frame:
January 2003 to December 2013.
1127 kidney transplants (KT).
Immunosuppressive regimen differed according to different transplantation eras and
different populations.
were divided in 3 groups according to donor age:
group A (< 50 years), group B (50–69 years),
group C ≥ 70 years.
The outcomes were analyzed for patients with at least 1 year of follow-up according to 1-
year post-KT extent.
when comparing 6-month and 1-year proteinuria, the latter showed a better correlation
with death censored graft survival (DCGS).
Regarding 1-year PTO we used a cut-off (0.5 g/ day).
, eGFR value at 1-year post-KT showed the best correlation with DCGS (AUC 0.74)
and its median value in the whole population was 44.24 ml/min.
Main outcomes were death censored graft survival (DCGS) and patient survival
Results:
Assuming 0.5 g/day as proteinuria cut-off, the association of 1-year PTO with DCGS and
graft survival was present for all donor age classes.
the impact of proteinuria on patient survival was noted only for younger donors.
Karpinsky score as well as glomerulosclerosis score were not associated with DCGS
differences.
6mo-1 yr. proteinuria increase was not associated with patient survival at any donor age
(p = 0.71) On the contrary, any increase of proteinuria between these time points was
associated with poor graft survival and DCGS (AUC 0.6;)
Early adverse events (during first post KT year):
1-year post-KT proteinuria > 0.5 g/day was associated with new onset diabetes,
glomerulonephritis and rejection. also transplant urologic complications and
Cytomegalovirus viremia.
EGFR strongly associated to patient, graft and DCGS (91.2% with eGFR ≥44 ml/min
versus 65.2% with eGFR < 44 ml/min.
In this multivariate analysis 1-year PTO ≥ 0.5 g/day, donor age ≥ 70 years, 1-year eGFR
< 44 ml/ min and the onset of CMV viremia in the first year were independently
associated with DCGS.
Discussion :
For the general population, the risk of adverse outcomes (mortality, progression to end-
stage renal disease) increases with higher levels of albuminuria.
study demonstrated that occurrence of proteinuria,(≥ 0.5 g/day), at the first post-
transplant year, was significantly linked to graft survival and patient survival in the whole
population under study.
synergic effect of proteinuria ≥0.5 g/day and donor age ≥ 70 years on DCGS.
Very low grade proteinuria (between 0.2 and 0.5 g/ day) was not related to outcome.
Nevertheless, there’s a demonstrated association (a trend, not reaching significance)
between DCGS and low-grade PTO (≥ 0.2 < 0.5 g/day) only in kidneys from donors older
than 70 years old.
Conclusion:
other causes of proteinuria should be excluded (e.g., cardiovascular diseases,
infections, metabolic comorbidities), close monitoring of proteinuria should be repeatedly
performed.
Level of evidence lll
Proteinuria should be followed in PTO carful.
Monitoring. And control of other risk factors should be considred
In high risk patient I.e older donors protocol. Biopsy should be considered.
Proteinuria is known to be an independent risk factor for cardiovascular disease and mortality in native kidneys as well as an indicator of renal damage and a predictor of allograft loss after kidney transplantation.Even if older donor age is mentioned as risk factor for development of post-KT proteinuria, the effective impact of proteinuria in recipients of elderly donors is not clearly defined and studied.In this article by Diena and collaegues have tried to explore this relationship.
This study investigated the impact of post transplant proteinuria in the first year in 1127 kidney transplants analyzing the impact of different donor ages. Proteinuria cut off was set at 0.5 g/day
They performed a retrospective observational cohort study including all deceased donor grafts performed at Turin University Renal Transplant Center “A. Vercel- lone” from January 2003 to December 2013.
The recipients’ follow-up was performed with scheduled clinical visits for the entire follow-up and hospital admis- sions when major complications occurred.
Post-transplant renal biopsies were performed for cause (mainly when serum Creatinine increased ≥20% of baseline value or with proteinuria > of 0.5–1 g/day).
Patients were divided in 3 groups according to donor age:
group A (< 50 years)
group B (50–69 years)
group C ≥ 70 years..
The outcomes were analyzed for patients with at least 1year of follow up.
Conclusions: Post-transplant proteinuria was increasingly harmful with older donor age. Proteinuria ≥0.5 g/day correlates with worse outcomes in all transplanted patients.
The role of ACE inhibitors/ARBs in the transplant patient is incompletely defined.
When used in combination with CNI it can lower GFR and in early transplant period can create confusion for detection early rejection
Can cause hyperkalemia
Worsens or induce Anemia
Ideally we should to wait three to six months posttransplantation for the institution of an ACE inhibitor or an ARB, if indicated.
Proteinuria post-transplantation has been associated with worse graft outcomes. The study was conducted to assess the effect of proteinuria (more than 500 mg/day) in first year post-transplant, with respect to the donor age, on graft and patient outcomes.
The study included 1127 deceased donor kidney transplants performed at Turin university transplant centre between 2003 and 2013. They were divided into 3 groups on the basis of donor age (A:<50, B:50-69, and C: > 70 year age). Proteinuria at 6 -12 moths was evaluated. The number of patients in the 3 groups were 339, 496 and 292 respectively. Mean follow-up was for 8.21 years.
One year proteinuria >500 mg/day was associated with death censored graft survival (DCGS) and graft survival for all donor ages while patient survival was affected only in younger age group. Low grade proteinuria (200-500 mg/day) was associated with lower DCGS among group C, although not significant.
There was significant difference with respect to total Karpinsky score in kidney biopsy with respect to the donor age, higher glomerulosclerosis score showed good correlation with higher 1 year proteinuria. Any increase in proteinuria between 6- and 12-months post-transplant was associated with poorer graft survival and DCGS, more so in recipients of older donors, while there was no effect on patient survival.
The time to graft failure was higher in group A (6 years) than group C (3 years). Patients with an increase of more than 100 mg/day proteinuria between 6 and 12 moths post-transplant had lower DCGS (69.9% versus 90.2% for those with increase of less than 100 mg/day in the 2 time points).
One year post-transplant proteinuria was associated with increased DGF, increased NODAT, glomerulonephritis and rejection, transplant urological complications (ureteral stenosis and ureteral fistulas) and CMV viremia in predicting poorer graft outcomes.
One year eGFR <44 ml/min had poor DCGS, graft and patient survival. On multivariate analysis, one year proteinuria > 500 mg/day, eGFR < 44 ml/min, donor age > 70 years and onset of CMV infection within first year was associated with poor DCGS. Rejection was also an important component, if taken for entire follow-up, not for first year alone.
A proteinuric kidney, when compared to non-proteinuric kidney from same donor was found to have increased DGF, increased ureteral stenosis, rejection, and glomerulonephritis as well as poorer DCGS, especially if the donor was > 50 years age.
The study also showed that use of ACE inhibitors/ARBs decreased proteinuria and eGFR but there was no improvement in patient and graft survival in post-transplant proteinuria.
The strengths of the study include homogeneity of the population, wide range of data with large study pool, long-term follow-up of the study population and use of paired kidney data from same donor for validation of the results with respect to proteinuria.
The limitations of the study include absence of a protocol graft biopsy, absence of DSA profile, and absence of qualitative differentiation of proteinuria in the study.
The study concluded that post-transplant proteinuria is associated with poorer outcomes even in early post-transplant period and hence close monitoring is essential, especially with elderly donors and proteinuria will warrant a kidney biopsy for ascertaining the cause, even in absence of DSA.
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.
Ours is a live donor transplant program. We screen the prospective donor for albuminuria during pre-transplant evaluation.
Post-transplant, close follow-up regarding proteinuria is kept in the recipient and if proteinuria is more than 500 mg/day, then kidney biopsy is performed to ascertain the cause.
This is a single-center, retrospective observational cohort study (level of evidence IIb) from January 2003 to December 2013 to assess the impact of the degree of proteinuria after one year of transplantation and its impact on graft loss and other complications. clinical variables related to renal function.
The regimens adopted in induction could be related to methylprednisolone, basiliximab, and thymoglobulin, most of them adopting the triple suppression regimen in maintenance. Biopsies were generally not performed on donors younger than 50 years, but all donors older than 70 years were performed. Three groups were separated by age (A < 50 years, B 50 to 69 years, and C > 70 years.
Some variables were included, proteinuria at one year, age of donor, age of recipient, eGFR, DGF, rejection, and CMV infection in the first year).
1127 patients were selected (A 339, B 496, C 292). Proteinuria was associated with poorer graft survival, particularly when donors were older (>70 years). Proteinuria > 0.5g/day was related to the onset of diabetes, glomerulonephritis and rejection. CMV infections also play an important role in this group of patients. eGFR < 44mL/min completes these independent variables.
The impact of proteinuria has already been shown in previous studies, but in this study at the end of one year with > 0.5g/day it is related to graft loss, especially with donors over 70 years of age. In this age group you can see loss of function even in smaller spectra of proteinuria (0.2 to 0.5g/day). These findings suggest that proteinuria may be a marker of graft loss of function.
The study stands out for the homogeneity of the population evaluated by the same multidisciplinary team, including a screening for the evaluation of very broad proteinuria of donors. Limitations are related to lack of protocol kidney biopsies and differentiation of proteinuria in the samples.
Therefore, evaluating the proteinuria of these donors in our service tends to be easy, inexpensive and can provide data on the short-term consequences of the grafts and the risks involved.
INTRODUCTION
Research and studies are being conducted globally to expand the living donor pool and reduce the wait list for transplant by including as much possible marginal donors. But the foremost principle in implementing the same is not to pose risk for the donor after donation.
Among this category old age donation is important aspect of consideration. But older graft kidneys have increased chance of having poor renal reserve and delayed graft function. Proteinuria is known to be an independent risk factor for cardiovascular disease and mortality in native kidneys as well as an indicator of renal damage and a predictor of allograft loss after kidney transplantation.
Old age donation is one of the major risk factors of development of post transplant proteinuria.
So the study was conducted to analyze the impact of differ- ent degrees of 1-year proteinuria on patient and graft survival in kidney transplants from different donor ages and to evaluate the correlation between proteinuria and donor or recipient risk factors with graft loss.
METHODS
Reterospective observational cohort study which included all deceased donor grafts.
‘Study period was from Jan 2003 to Dec 2013.
Immunosuppressive regimen differed according to different transplantation eras and different populations. The most adopted schedules were: induction with steroid boluses, rapidly tapered to 20mg/day of oral prednisone and two doses of anti-CD25 antibody. Subjects at high immunological risk (e.g. previous transplant lost for acute rejection, high PRA titer) were treated with antithymocyte globulin. Maintenance therapy was generally based initially on a triple-drug protocol. Calcineurin in- hibitor (CNI), either tacrolimus or Cyclosporine, was associated to Mofetil Micofenolate/Micophenolic Acid or Azathioprine and prednisone.
Patients were divided in 3 groups according to donor age: group A (< 50 years), group B (50–69 years), group C ≥ 70 years.. The outcomes were analyzed for patients with at least 1year of follow-up according to 1-year post-KT extent.
‘At one year post transplant outcome, proteinuria was defined as 0.5 GM/day with low grade proteinuria being 0.2gm/day to 0.5gm/day.
Main outcomes were death censores graft survival and patient survival.
RESULTS
Analysis included 1127 kidney recipients, transplanted at Turin University Renal Transplant Center
DISCUSSION
The deleterious effects of proteinuria in early post transplant period and it’s adverse impact long term outcomes have been clearly demonstrated in previous studies. But harmful levels of proteinuria and their time points are not clearly defined.
The current study demonstrated that :
Strengths:
Limitations
This is retrospective observational cohort study
At Turin renal transplantation center
From J 2003 to D 2013
Containt deceased donor grafts (with extended criteria)
1127 kidney transplants
Group a less than 50 years n=339
Group b 50 69 years n = 496
Group c more than 70 years n= 292
Follow up 8 years
Results
DCGS of patients with donor age≥70 years and higher 1-year proteinuria was only 29.7% versus 72.3% in recipients of kidneys from younger donors with the same proteinuria (p =0.03).
impact of low grade proteinuria (0.2–0.5g/day) did not show any significant association of 1-year PTO with patient and graft survival and DCGS at any donor age.
6 mo1 yr proteinuria increase was not associated with patient survival at any donorage (p=0.71).
But was associated with poor graft survival
ACEi and ARBs therapy didn’t influence 6 months- 1 year proteinuria variations
1 year post KT proteinuria > 0.5 g / day was associated with new onset DM – GN- rejection.
1-year PTO≥ 0.5 g/day, donor age≥70years, 1-year eGFR <44ml/ min and the onset of CMV viremia in the first year were independently associated with DCGS
This study demonstrated that occurrence of proteinuria,(≥ 0.5 g/day), at the first post-transplant year, was significantly linked to graft survival and patient survival
Assosiation between DCGS and low-grade PTO (≥ 0.2 < 0.5g/day) only in kidneys from donors older than 70years old
early post KTevents (acute rejection, CMV infections, new onset diabetes after transplantation and urological complications such as ureteral stenosis) contribute to determine kidney fate and prognosis
Conclusion
the presence of proteinuria in the first year at a relatively low extent (0.5 g/day), even in the absence of donor specific antibodies, should suggest a careful evaluation.However ,utility of protocol biopsy is still debated
Level III
BTS GUIDELINE for living donor
Urine protein excretion needs to be quantified in all potential living donors. (B1)
(ACR) performed on a spot urine sample is the recommended screening test, although (PCR) is an acceptable alternative. (A1)
ACR >30 mg/mmol, PCR >50 mg/mmol, albumin excretion >300 mg/day or protein excretion >500 mg/day represent absolute contraindications to donation. (C2)
The significance of moderately increased albuminuria (ACR 3-30 mg/mmol) and proteinuria (PCR 15-50 mg/mmol or 24-hour urine protein 150-500 mg/day) has not been fully evaluated in living kidney donors. However, since the risk of CKD and cardiovascular morbidity increase progressively with increasing albuminuria or proteinuria such levels are a relative contraindication to donation. (C2)
In our practice we exclude any donor with proteinuria more than 150 to 200 after repeating urinary test in several occasions
This case-control study has level 3 of evidence.
………
Proteinuria is known as an independent risk factor for graft loss after transplantation. optimally evaluated after the 3rd month-12 months. With variable hazard ratios, most studies showed the negative impact of proteinuria in the early period. In Cantarovich et al. study, this was not significant at the 5th year. This study aimed to evaluate the impact of different degrees of proteinuria from different ages of donor groups. The evaluation of proteinuria in the study included cases from 2003-2013 that included variable immunosuppressive regimens. Tacrolimus was %80 used. Evaluation of proteinuria was assessed at 3,6, 12, 24 months and 5th year. eGFR was evaluated by CKD-EPI 2009 (not stated; CDK-EPI 2021 is released after publication). Pre-transplant biopsies were mostly performed mostly from donors over 50 years. Post-transplant biopsies were mostly due to cause (generally 20% or more increase in Scr or >0.5-1 gram of proteinuria. A dedicated group of pathologists performed the evaluations. patients were stratified as <50, 50-69 and >70 and grouped as A, B, and C, respectively.
Analysis included 1127 (A:339, B:496, C:292 patients). In this study, the effect of proteinuria of more than 0.5 gr/day and the effect of age over 70 was linked to delayed kidney function.
Older living donor show increase in proteinuria post donation
Post-transplant proteinuria was increasingly harmful with older donor age. Proteinuria ≥0.5 g/day correlates with worse outcomes in all transplanted patients. Prognostic value of proteinuria and eGFR for graft and patient survival was comparable and these two variables remain significant risk factors even in a multivariate model that take into consideration the most important clinical variables (donor age, rejection, delayed graft function and cytomegalovirus viremia among others).
Assuming 0.5 g/day as proteinuria cut-off, the association of 1-year PTO with DCGS and graft survival was present for all donor age classes (Table 2); the impact of proteinuria on patient survival was noted only for younger donors. Donor age increased the magnitude of proteinuria impact: DCGS of patients with donor age ≥ 70 years and higher 1-year proteinuria was only 29.7% versus 72.3% in recipients of kidneys from younger donors with the same proteinuria
Our study demonstrated that occurrence of proteinuria,(≥ 0.5 g/day), at the first post-transplant year, was significantly linked to graft survival and patient survival in the whole population under study. For the first time in literature, to the best of our knowledge, the impact of proteinuria on KTs from different donor age classes was analyzed, demonstrating a synergic effect of proteinuria ≥0.5 g/day and donor age ≥ 70 years on DCGS.
Very low grade proteinuria (between 0.2 and 0.5 g/ day) was not related to outcome. Nevertheless, we demonstrated an association (a trend, not reaching significance) between DCGS and low-grade PTO (≥ 0.2 < 0.5 g/day) only in kidneys from donors older than 70 years old. (Fig. 3).
Older donor kidneys seemed more sensitive to proteinuric injuries in comparison with younger ones with very relevant differences of DCGS in different donor age classes with same proteinuria. This is also highlighted by the fact that any variation of proteinuria between 6 months and 1 year post-KT portends a worse graft outcome when donor age was ≥60 years
the evidence suggesting a benefit for ACEi/ ARB use in transplant recipients is still lacking. They showed that the use of these agents was often associated with a significant reduction in proteinuria and eGFR without a concurrent improvement of patient or allograft survival as it does in non-transplant settings such as in diabetic nephropathy
level III
As in previous articles, there is a large number of kidney failures and a great need for kidney transplantation. This article provides information about how proteinuria may impact graft survival and its relation with the age of the donor. Proteinuria is a risk factor for kidney disease and as the amount increases, it shows or provides information about worsening kidney functions. Not only is it present in the case of kidney disease but also it is related to CVD and endothelial lesions.
So the study tries to analyze the impact of proteinuria at the different grades of 1 year on patients and how it impacts to graft survival from the different donor age groups. It deals with the correlation between proteinuria, donor and recipient risk of losing the graft, and finally, if proteinuria is a risk factor for graft survival.
The study was a retrospective observational cohort study conducted at the Turin transplant center for a period of 2003-2013 about 10 years. There were about 1127 deceased donors and the study was approved by the relevant committees.
After an intense investigation, results were obtained and summarised as follows:
1) A proteinuria greater than 0.5g/day results in a poor graft outcome in all the donor groups.
2) An increase in proteinuria for a period of 6 months to 1 year had a negative impact on donors greater than 60 years and an increase of proteinuria greater than 0.5 g/day increased graft failure.
3) An increase in donor age with a low grade that is 0.2-0.5 g /day of proteinuria tends to worsen graft survival.
4) And proteinuria greater than 0.5 g/day also affects doors older than 50 years old.
5) It was also noted that the use of ACEI AND ARBs would decrease proteinuria but not graft survival.
The likely explanation for the formation or worsening proteinuria is due to tissue damage like intratubular, the activations of compliments, the presence of free radicals, etc.
Medications have been tried to resolve the proteinuria and improve kidney function like ACEI, ARBs, and immunosuppress like mTOR inhibitors. Even with the use of the mentioned medications, there were no drastic kidney functions, and the kidney progressed to failure.
There were certain factors that limited the study and they are the absence of donor-specific antibody evaluation during the first year and the population was not evaluated in this aspect. The proteinuria was not specific regarding if it is tubular from glomerular.
The study was a good one due to the fact that there was a large population and involve not only nephrologists but also other specialties. The data collection was from a large population which made biases less likely.
So one can conclude that proteinuria whether a mild amount will have a negative impact on graft survival and also on the donors. Care must be taken to ensure a proper investigation is conducted so as to avoid problems and have better graft outcomes and donors.
This article is likely to be a level 3 study.
In my practice, close consideration must be taken to ensure that patients are studied well and close monitoring must be conducted to ensure there are limited errors and to salvage grafts, donors, and recipients.
Accepting donors with suboptimal organs including elderly is an approach used to increase the donor pool and shorten the waiting time.
“Old for old strategy” and correct allocation policy provided the same death censored graft survival among donor decades.
Proteinuria is a risk factor for CVD and predictor of allograft loss post transplant but the impact of proteinuria in recipients of elderly donors on graft survival is not well determined.
In several studies, proteinuria was associated with poor graft outcome and was a significant prognostic factor.
This study aimed to determine the impact of one year proteinuria on graft and patient survival and to evaluate the correlation between proteinuria and donor or recipient risk factors with graft loss.
It included 1127 consecutive deceased donor kidney transplantation with exclusion of multiorgan transplants.
Serum creatinine and proteinuria were assessed at discharge, at 3, 6 months and at 1,2 and 5 years post transplant.
GFR was estimated by CKD-EPI equation
Pre-transplant donor biopsy were not routinely performed in donors <5 years and were always performed in those >70 years and individualized in donors 50-70 years according to several characteristics
Post transplant biopsies were performed for cause only.
Patients were divided according to donor age <50 years, 50-69 years and >70 years, the main outcomes were DCGS and patient survival.
The study showed that proteinuria>0.5g/day in the first year post transplant is significantly associated with patient and graft survival.
Both proteinuria >0.5g/day and donor age >70 years had synergistic effect on DCGS.
Proteinuria between 0.2 and 0.5 was associated with DCGS only in kidneys from donors older than 70 years.
Also, variation of proteinuria between 6 months and one year post transplant predict poor graft outcome when donor age is >60 years.
Proteinuria is considered as a marker of loss of kidney function.
Rejections, number of biopsies, NODAT and GN were associated with higher one year proteinuria with similar distribution between donor age group.
The study showed prognostic significance of proteinuria in donors suboptimal organs.
It suggested that elderly donors with proteinuria should be closely monitored and presence of proteinuria >0.5g/day in first year post transplant necessitate careful assessment and may indicate for-cause biopsy.
Strengths:
Included homogenous population.
Analyzed paired kidneys which limited undetermined donor related confounding factors.
Limitations:
Protocol biopsy was not performed
DSA was not routinely evaluated in the first year
No qualitative differentiation between tubular and glomerular proteinuria
Level 2, observational retrospective cohort study
We don’t have deceased donor transplant, we screen patients for proteinuria regularly every 3 months post transplant in the first year.
Proteinuria is known to be an independent risk factor
for cardiovascular disease and mortality in native kidneys as well as an indicator of renal damage and a predictor of allograft loss after kidney transplantation
Halimi and coworkers showed a strong correlation of 1- and 3-month proteinuria
(per every 0.1 g/day increase) with graft loss
Amer and colleagues analyzed 1-year post KT proteinuria finding an Hazard Ratio (HR) for graft loss of 2.15 (CI 95% 0.68–6.8), associated with proteinuria between 150 and 500 mg/day and an HR of 5.11 (CI 95% 1.4–19.2) with higher level of proteinuria
Aim of this study was to analyze the impact of different degrees of 1-year proteinuria on patient and graft survival in kidney transplants from different donor ages and to evaluate the correlation between proteinuria and donor or recipient risk factors with graft loss. A secondary aim is to evaluate proteinuria as risk factor for kidney graft survival in multimodal models taking into account renal function and other main clinical variables.
Methods Study design
a retrospective observational cohort study including all deceased donor grafts performed at Turin University Renal Transplant Center “A. Vercellone” from January 2003 to December 2013. The study was submitted and approved by the local ethics committee (ethics committee of “Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino”/ University of Turin).
Immunosuppressive regimen differed according to different transplantation eras and different populations.
Maintenance therapy was generally based initially on a triple-drug protocol. Calcineurin inhibitor (CNI), either tacrolimus (80% of cases) or Cyclosporine, was associated to Mofetil Micofenolate (Cell Cept, Roche, Basel, Switzerland)/Micophenolic Acid (Myfortic, Novartis, Basel, Switzerland) or Azathioprine and prednisone.
The recipients’ follow-up was performed with scheduled
clinical visits for the entire follow-up and hospital admissions when major complications occurred.
creatinine and proteinuria (in 24-h urine collections) were assessed at discharge, at 3, 6 months and at 1, 2 and 5 years after transplantation. Renal allograft function (eGFR) was estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Pre-transplant donor biopsies were performed on the basis of a multidimensional assessment including macroscopic appearance, renal function, donor comorbidities and echographic characteristics
Post-transplant renal biopsies were performed for
cause (mainly when serum Creatinine increased ≥20% of baseline value or with proteinuria > of 0.5–1 g/day).
Patients were divided in 3 groups according to donor
age: group A (< 50 years), group B (50–69 years), group C ≥ 70 years.. The outcomes were analyzed for patients with at least 1 year of follow-up according to 1-year post-KT extent. To eliminate confounding factors, as native kidneys proteinuria, we mainly explored proteinuria values after the sixth post-KT month; when comparing 6-month and 1-year proteinuria (1-year PTO), the latter showed a better correlation with death censored graft survival (DCGS) with an AUC 0.64 vs 0.59
Results and Discussion
For the general population, the risk of adverse outcomes (mortality, progression to end-stage renal disease) increases with higher levels of albuminuria so that it was included in 2012 Kidney Disease Improving Global Outcomes guidelines as key marker for chronic kidney disease (CKD)
Numerous studies in patients with diabetic and nondiabetic renal diseases confirm that marked albuminuria (> 300 mg/day) is associated with a faster rate of CKD progression. On the contrary, moderate-level albuminuria (150–300 mg/day) is not a reliable surrogate marker for CKD progression in intervention clinical trials because reduction of albuminuria can be linked to both improving and worsening CKD progression
The study demonstrated that occurrence of proteinuria,(≥ 0.5 g/day), at the first post-transplant year, was significantly linked to graft survival and patient survival in the whole population under study.
Very low grade proteinuria (between 0.2 and 0.5 g/ day) was not related to outcome. Nevertheless, we demonstrated an association (a trend, not reaching significance) between DCGS and low-grade PTO (≥ 0.2 < 0.5 g/day) only in kidneys from donors older than 70 years old.
With ageing, kidney undergoes through processes that lead to reduced functional reserve and also to a lower renal reserve response to higher functional requests (e.g. protein load) due to a reduced capacity of renal autoregulation
proteinuria is not considered to be a “normal” physiological process of aging also in cases when the development of a persistent proteinuria increases with age, due to the higher prevalence of diabetes, hypertension and paraproteinemias
Predisposition to proteinuria development in our population appeared to be certainly related to both donor and recipient characteristics (donor age, pretransplant diabetes, glomerular Karpinsky score) but, as it is demonstrated by paired kidney analysis, early post- KT events (acute rejection, CMV infections, new onset diabetes after transplantation and urological complications such as ureteral stenosis) contribute to determine kidney fate and prognosis.
Among the other clinical variables, CMV viremia
post-transplant resulted as an independent predictor of DCGS in Cox multivariate analysis (HR 2.1), as mentioned in previous studies .As for rejection, when we consider rejection as an event in the entire follow-up, its role is comparable to the one of the other main risk factors (HR respectively 2.5 vs 2.1 and 2.4)
The link among proteinuria, donor age and subsequent higher proteinuria-mediated damage in older donors is an important issue of our study. Several mechanisms were advocated for proteinuria mediated tissue damage such as intratubular complement activation , intratubular protein overload ,radical oxygen damage induced by tubular reabsorption of iron carrying proteins such as transferrin
Strenghts points of the study are related to homogeneity of the population, characterized by a wide range of data coming from over a thousand of KTs performed with the same team of surgeons, nephrologists and pathologists. Patients were centrally followed in the long term with all data recorded in patients’ charts.
Another strength, in our opinion, is the validation of
prognostic impact of proteinuria in a subset of paired kidneys, thus limiting undetermined donor-derived confounding factors
Other limitations are: absence of routinely donor specific antibody evaluation in the first year, which was available only in a minority of patients, so that we did not evaluate our population under this aspect; moreover lack of qualitative differentiation of urinary protein, considering that tubular or glomerular proteinuria could have different impact on graft outcome, as underlined in previous studies
Conclusion
Clinicians often do not know how to handle early low-grade proteinuria given the fact that it is often considered as aspecific, possibly due to native kidneys residual function (in the early period). Our study clearly evidence that proteinuria is always deleterious to transplant outcome even at early follow up time point. Based on our results we suggest that, in the context of elderly donors and in the absence of acknowledged effective pharmacological tools, when other causes of proteinuria are excluded (e.g. cardiovascular diseases, infections, metabolic comorbidities), close monitoring of proteinuria should be repeatedly performed.
the presence of proteinuria in the first year at a relatively low extent (0.5 g/day), even in the absence of donor specific antibodies, should suggest a careful evaluation of patients leading to for-cause biopsy. Utility of protocol biopsy in patients with nonstandard donor, even in the absence of risk factors, should be ascertained by further studies.
level III
We do 24 hr urine collection for protein at discharge of our patient and then at 3, 6 months and at 1, 2 and 5 years after transplantation.if more than 500 mg / day we do renal biopsy
we didn’t do protocol biopsy
this is RCT trial which showed no benefit from using ACEI OR ARB IN REDUCING protienuria post donation .
there is contradiction in this issue between different study some of them supporting the use of ramipril.
EExcellent article detailing the importance of proteinuria and its correlation with graft survival and patient survival. it was great to know about the correlation of donor age and the proteinuria post transplant.
however in my opinion rather than one static value of proteinuria, it would be more prudent to see the trend proteinuria in follow up.since many of the recipients have proteinuria coming from the native kidneys, especially the ons who were non oliguric before the transplant, I would be sceptical in commenting on a single or two values of proteinuria, rather follow the trend over thee times period to decide my future interventions. would also like to qualify whether it is actually albuminuria rather than proteinuria alone.
Please summarise this article in your own words
-Over the past decades, increase of donor pool by using elderly donors has been largely adopted to reduce kidney transplant (KT) waiting list .Nevertheless, death censored graft survival does not change among donor decades if a correct allocation policy is performed .
-Proteinuria is known to be an independent risk factor for cardiovascular disease and mortality in native kidneys as well as an indicator of renal damage and a predictor of allograft loss after kidney transplantation . Optimal timing for measuring proteinuria is between 3 months and one year post-KT.
-Aim of this study was to analyze the impact of different degrees of 1-year proteinuria on patient and graft survival in kidney transplants from different donor ages and to evaluate the correlation between proteinuria and donor or recipient risk factors with graft loss.
-A secondary aim is to evaluate proteinuria as risk factor for kidney graft survival in multimodal models taking into account renal function and other main clinical variables.
-It is a retrospective observational cohort study including all deceased donor grafts performed at Turin University Renal Transplant Center
from January 2003 to December 2013.
-It was analyzing the 1127 consecutive kidney transplants (KT).
-The study demonstrated that occurrence of proteinuria,(≥ 0.5 g/day), at the first post-transplant year, was significantly linked to graft survival and patient survival
in the whole population under study.
-Older donor kidneys seemed more sensitive to proteinuric injuries in comparison with younger ones with very relevant differences of death censored graft survival (DCGS) in different donor age classes with same proteinuria.
-Predisposition to proteinuria development in the study population appeared to be certainly related to both donor and recipient characteristics (donor age, pretransplant diabetes, glomerular Karpinsky score) but, as it is demonstrated by paired kidney analysis, early post- KT events (acute rejection, CMV infections, new onset diabetes after transplantation and urological complications such as ureteral stenosis) contribute to determine kidney fate and prognosis.
-1-year proteinuria ≥0.5 g/day is comparable to CKD-EPI < 44 ml/min in predicting graft failure by multivariate analysis and donor age ≥ 70 years would make this association even worse.
– Several mechanisms were advocated for proteinuria mediated tissue damage such as intratubular complement activation , intratubular protein overload , radical oxygen damage induced by tubular reabsorption of iron carrying proteins such as transferrin .
-Older donor kidneys may potentially be more sensitive to such mechanisms, even with a lower grade of proteinuria.
-The previous studies and confirmed by this study data, the evidence suggesting a benefit for ACEi/ ARB use in transplant recipients is still lacking. They showed that the use of these agents was often associated with a significant reduction in proteinuria and eGFR without a concurrent improvement of patient or allograft
survival as it does in non-transplant settings such as in diabetic nephropathy .
-It is well known that mTor-inhibitors may induce proteinuria by targeting glomerular podocytes . This is confirmed also in our cohort. However, excluding patients with mTor maintenance therapy in the first year , the impact of proteinuria on outcome was confirmed.
-Strenghts of the study are related to homogeneity of the population, characterized by a wide range of data coming from over a thousand of KTs performed with the same team of surgeons, nephrologists and pathologists.
Patients were centrally followed in the long term with all data recorded in patients’ charts.
-Another strength point, is the validation of prognostic impact of proteinuria in a subset of paired kidneys, thus limiting undetermined donor-derived confounding
factors .
-The limitation of this study is the absence of protocol graft biopsies for center policy; however, this limitation reduces its importance when we consider that proteinuria impact was shown by some authors to be independent from the underlying renal allograft histology .
-Other limitations are: absence of routinely donor specific antibody evaluation in the first year, which was available only in a minority of patients, so that we did
not evaluate our population under this aspect; moreover lack of qualitative differentiation of urinary protein, considering that tubular or glomerular proteinuria could have different impact on graft outcome, as underlined in
previous studies .
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, urinalysis should be done in every follow-up to detect any abnormality like proteinuria. We have no protocol biopsy, only diagnostic biopsy if it is indicated.
This is a retrospective cohort study (level of evidence II) evaluating 1127 kidney transplants recipients who received deceased kidneys from donors with different age groups regarding the impact of proteinuria (> 0.5 g/d) (evaluated by 24h urine collection) occurring in the first-year post-transplantation on graft (eGFR estimated by CKD-EPI) and recipient outcome and its relation to the donor age.
Methods:
a retrospective observational cohort study done in Turin University Renal Transplant Center from January 2003 to December 2013 on 1127 deceased donor kidney transplants.
Recipients were divided into 3 groups according to their donor age: group A (< 50 years), group B (50–69 years), and group C ≥ 70 years.
The outcomes were analyzed for patients with at least 1 year of follow-up according to 1-year post-KT extent.
Results:
Conclusion:
Please reflect on the guidelines and refer to your practice:
· We follow proteinuria post-transplant in every OPD visit.
· Persistent proteinuria of more than 1gm measured by 24h urinary protein is an indication for kidney biopsy
Proteinuric recipients with stable graft function after 3 months post-transplant and no hyper K are candidates for ARBs and ACEI with close monitoring of S.k and UE1 for the 1st 2w after adding these medications
Thank you
Please summarise this article in your own words
Introduction
Proteinuria is an independent risk factor
for CVD & mortality in native kidneys. It is also an indicator of graft damage & predicts allograft loss after KT.
Measuring proteinuria between 3 months & 1 year post-KT will help to detect ongoing damage & to adopt strategies to prevent further progression.
The study
Aim:
·To analyze the impact of different grades of 1-year proteinuria on patient & graft survival in KT from different donor ages.
·To evaluate the correlation between proteinuria & donor or recipient risk factors with graft loss.
·To evaluate proteinuria as risk factor for kidney graft survival in multimodal models.
Methodology
Retrospective observational -Cohort study at Turin Transplant Centre from 2003 -2013. 1127 deceased donors were included. Approval from local ethical committee . Those with multi organ graft were excluded.
Results:
*Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age groups.
*The 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old (p < 0.05; Odd Ratio 1.8). 1-year graft function (eGFR < or ≥ 44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure (Hazard Ratio 2.77 vs Hazard Ratio 2.46).
* Low-grade proteinuria (0.2–0.5 g/day) demonstrated a trend for worse graft survival with increasing donor age.
*In kidney-paired analysis proteinuria ≥0.5 effect was more significant with donors > 50 years old.
#Strenghts of the study:
*Related to homogeneity of the population, characterized by a wide range of data coming from over a thousand of KTs performed with the same team.
*Patients were centrally followed in the long term with alldata recorded in patients’ charts.
*Validation of prognostic impact of proteinuria in a subset of paired kidneys, thus limiting undetermined donor-derived confounding factors.
# Limitation of this study:
*Absence of protocol graft biopsies for center policy.
*Absence of routinely donor specific antibody evaluation in the first year.
*Lack of qualitative differentiation of urinary protein.
#Conclusions
Post-transplant proteinuria was increasingly harmful with older donor age. Proteinuria ≥0.5 g/day correlates with worse outcomes in all transplanted patients. Prognostic value of proteinuria and eGFR for graft and patient survival was comparable and these two variables remain significant risk factors even in a multivariate model that take into consideration the most important clinical variables (donor age, rejection, delayed graft function and cytomegalovirus viremia among others).
# What is the level of evidence provided by this article?
*It is retrospective observational cohort study level 3.
# Please reflect on the guidelines and refer to your practice.
*We don’t have deceased donation in our country, but in case of old donors we follow up the patient regularly every month for 3 months then every 2 months with RFT and urine analysis if there any possibility of proteinuria we do ACR, 24 hour urine protein and we can go further to renal biopsy.
Thank you
Please summarise this article in your own words
This study was conducted at Turin renal transplant centre. It was aimed to find the relation between proteinuria and donor/recipient risk factors with graft loss. It also attempted to establish relationship between different degrees of proteinuria with graft and patient outcomes in different age groups. It also tried to establish proteinuria as a risk factor for graft survival.
Methodology
Retrospective observational -Cohort study at Turin Transplant Centre from 2003 -2013. 1127 deceased donors were included. Approval from local ethical committee . Those with multi organ graft were excluded.
Variables Checked-
eGFR Check by CKD-EPI
24 Hour urine protein and creatinine check at -Discharge, 3, and 6 months and at 1, 2,5 years.
Post transplant biopsies were done where indicated
Donor age groups-
A- <50
B- 50-69
C->70
Outcome analyzed with at least 1 year follow up
Results-
Proteinuria >0.5 gram per day is related to poor graft outcomes
Low scale proteinuria was related to poor graft outcome with increasing age.
High proteinuria between 6 -12 moths was associated with poor graft outcomes.
Transplant complications and CMV viremia was associated with proteinuria
Strengths- Large population. Long follow up
Limitations- Absence of protocol biopsies, No routine check for DSA
Conclusion-
Proteinuria is always bad for graft
Proteinuria > 0.5 g/day is associated with poor graft outcomes.
Proteinuria is more harmful in higher age groups
proteinuria and eGFR have similar prognostic value.
Close monitoring for proteinuria is essential
What is the level of evidence provided by this article?
Cohort study Level 11
Please reflect on the guidelines and refer to your practice.
In my country only live donation is practiced. donors are followed 3 monthly in first year with renal functions and urine test.
Thank you
Relationship between early proteinuria and long-term outcome of kidney transplanted patients from different decades of donor age.
Summary of the article:
This is a retrospective observational cohort study including all deceased donor grafts performed at Turin University Renal Transplant Center, from January 2003 to December 2013( Mean follow-up was 8.21 years), analyzing 1127 consecutive kidney transplants (KT). Patients were divided in 3 groups according to donor age: group A (< 50 years), group B (50–69 years), group C ≥ 70 years. Creatinine and proteinuria (in 24-h urine collections) were assessed at discharge, at 3, 6 months and at 1, 2 and 5 years after transplantation. Proteinuria cut off was set at 0.5 g/day, with further analysis to low-grade proteinuria (between 0.2 g/day and 0.5 g/day). The main outcomes were death censored graft survival (DCGS) and patient survival.
Study Results and outcome
1. In the low grade proteinuria group(0.2-0.5g/day) univariate analysis did not show any significant association of 1-year PTO with patient and graft survival and DCGS at any donor age.
2. 0.5 g/day as cut-off proteinuria, the association of 1-year PTO with DCGS and graft survival was present for all donor age classes and the impact of proteinuria on patient survival was noted only for younger donors.
3. DCGS of patients with donor age ≥ 70 years and higher 1-year proteinuria was only 29.7% versus 72.3% in recipients of kidneys from younger donors with the same proteinuria.
4. 6mo-1 yr proteinuria increase was not associated with patient survival at any donor age, on the contrary, any increase of proteinuria between these time points was associated with poor graft survival and DCGS.
5. ACEi/ARB therapy did not influence 6mo-1 yr proteinuria variations. The evidence suggesting a benefit for ACEi/ ARB use in transplant recipients is still lacking.
6. 1-year eGFR was strongly associated to patient, graft and DCGS.
7. After using multivariate analysis considering the most relevant clinical variables of DCGS. The main predictors of DCGS(independently associated with DCGS):1-year post-transplant proteinuria ≥ 0.5 g/day, donor age ≥ 70 years, 1-year eGFR < 44 ml/ min and the onset of CMV viremia in the first year.
8. Rejection was a significant variable only when considered in the entire follow-up (not when 1st year rejections were considered).
9. Older donor kidneys seemed more sensitive to proteinuric injuries in comparison with younger ones with very relevant differences of DCGS in different donor age classes with same proteinuria.
10. 1-year proteinuria ≥0.5 g/day is comparable to CKD-EPI < 44 ml/min in predicting graft failure by multivariate analysis and donor age ≥ 70 years would make this association even worse.
Strenghts and Limitations of the study
Strengths:
a) Homogeneity of the population.
b) The validation of prognostic impact of proteinuria in a subset of paired kidneys.
Limitations:
a) The absence of protocol graft biopsies for center policy.
b) Absence of routinely DSA evaluation in the first year.
c) Lack of qualitative differentiation of urinary protein.
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?
We don’t proceed in the transplant process when the donor found to be with significant proteinuria.
Thank you
Introduction
Proteinuria known marker of kidney damage in both native kidneys and post-transplantation and is associated with poor outcomes.
The aim of this study
1. investigate the effect of various levels of 1-year proteinuria on patient and graft survival in kidney transplants from different donor ages
2. assess the correlation between proteinuria and donor or recipient risk factors with graft loss.
3. estimate proteinuria as a risk factor for kidney graft survival in multimodal reproductions taking into
account renal function and other key clinical variables.
Method and design of the study
A retrospective observational study from a local center including all deceased donor grafts completed at Turin University Renal Transplant Center. from Jan 2003-Jan2013, includes a total of 1127 kidney donors after exclusion of multiorgan transplantation and those with < than 6 months of FU patient data collected from medical records including the patient’s demographics, comorbidities, both e GFR (by using CKD EPI formula), and 24h urine protein records at discharge time than 3 months interval, 1, 2, 5 years’ time intervals of FU. Comorbid diseases, US abdomen, and donor biopsy at the time of donation done only for donors above 50 years, immunosuppressive therapy using basiliximab for standard risk with CNI based IS and early steroid tapering within 1-2 months ( CNI both cyclosporine and tacrolimus and 80% of cases using tacrolimus ), in high immunological risk they use ATG followed by triple maintenance, CNI use delayed till serum creatinine < 2.5mg in the immediate postoperative period with a target level of 12-15 in the first month then 8-10 in first 3 months, 5-8 after two years, m TOR conversion with CNI minimization after 6 months once indicated ( CNI toxicity ), post-transplant biopsy done only once indicated ( Scr increased by > 20%, and proteinuria > 0.5gm, both pre and post donation biopsies reviewed by the same pathologist. Karpinsky score was used to describe fitness for single or dual KT or refusal of organs.
Patients are classified into 3 groups based on their age of donation with at least 1 year FU post-transplantation
Group A < 50 years included 339
Group B 50-69 years included 496
Group C 70 -88 years included 292
The main outcomes were death-censored graft survival (DCGS) and patient survival. Graf function and post-KT complications were also analyzed.
They used UCA to determine the proteinuria time point with a strong association with DCGS.
Cumulative graft and patient survival were analyzed by Kaplan-Meier (KM) curves, a univariate model for the key clinically chosen covariates (1- year proteinuria, donor age, recipient age,
eGFR, DGF, rejection, 1-year Cytomegalovirus (CMV) infection)
Results
Total of 1127 DD kidney transplantations and as per the groups, group A 339, B 496, and C 292, with median FU 8.2 years the effect of proteinuria on patient survival was noted only for younger donors. Donor age increased the degree of proteinuria influence: DCGS of patients with donor age ≥ 70 years and higher 1-year proteinuria was only 29.7% versus 72.3% in recipients of kidneys from younger donors with similar proteinuria (p = 0.03). while a multivariate model considering the most relevant clinical variables: 1-year proteinuria,>0.5 gm/day donor age, recipient age, low eGFR, DGF, rejection, and 1-year CMV infection was independently associated with DCGS. Rejection was a significant variable only when considered in the entire follow-up (not when 1st-year rejections were considered a statistically higher rate of rejection and glomerulonephritis and a greater number of biopsies in the group with 1-year PTO ≥ 0.5 g/day. No significant variation was noted between the groups for the other analyzed variables.
1-year post-KT proteinuria > 0.5g/day was associated with new-onset diabetes (NODAT), glomerulonephritis, and rejection. Notably, also transplant urologic complications and Cytomegalovirus (CMV) viremia had an association with proteinuria. Biopsies were significantly more frequent in patients with higher 1-year proteinuria. total Karpinsky score, as well as glomerulosclerosis score, were not associated with DCGS differences. Better Cumulative survival with 1-year 24hurine proteinuria <0.2 for donors > 70 years.
Discussion
this study confirms the synergic effect of proteinuria≥0.5 g/day and donor age ≥ 70 years on DCGS.as with aging the functional capacity will be low with less autoregulation effect and exposure to multiple insults due to DM, HTN, and paraproteinemia which leads to compensatory hyperfiltration and proteinuria will be a marker of progression of chronic kidney damage
Strength of this study
large sample size with homogenous demographics and data
validation of the prognostic impact of proteinuria in a subset of paired kidneys, thus limiting undetermined donor-derived confounding factors
limitation
A retrospective design, local center.
lack of routine DSA antibody monitoring only a few have it in the first year
No protocol biopsy
lack of qualitative differentiation of urinary protein (tubular vs glomerular and its impact on the graft outcome)
Conclusion
The finding of clinical proteinuria in the first year (0.5 g/day), unfluctuating in the absence of donor-specific antibodies, should be evaluated, especially in the elderly. The utility of protocol biopsy in patients with modified donors, even in the absence of risk factors, should be determined by further studies.
Type of the study
Retrospective observational cohort study level 3
In our center we are mainly LRD program and proteinuria monitoring we do frequently, especially for those with primary Gn or a young with unknown primary or those with positive FH of CKD, however, we do graft biopsies once indicated we don’t have protocol biopsies and we don’t do DSA frequently.
Thank you Saja
☆Relationship between early proteinuria and long term outcome of kidney transplanted patients from different decades of donor age
♧Introduction:
▪︎There is an increase of donor pool by using elderly donors.“Old for old strategy” allowed a better allocation of kidneys matching the life expectancy of organs and recipients, even if elderly
kidneys have been shown to have a compromised renal reserve and more proclivity to nonspecific damages.
▪︎Conditions of ischemia-reperfusion damage & DGF increase the immunologic risk of such organs either through enhanced immunogenicity or through compromised repair mechanisms.
▪︎Death censored graft survival does not change among donor decades if a correct allocation policy is performed.
▪︎Proteinuria is a risk factor for CVD & mortality in native kidneys as well as an indicator of renal damage and a predictor
allograft loss after kidney transplantation.
▪︎The optimal timing for measuring proteinuria to detect ongoing damage is between 3months and one year post-KT.
▪︎The effective impact of proteinuria in recipients of elderly donors is not clearly defined and studied.
♧The aim of the study:
To analyze the impact of different degrees of 1-year proteinuria on patient and graft survival in kidney transplants from different donor ages and to evaluate the correlation between proteinuria and donor or recipient risk factors with graft loss.
▪︎A secondary aim is to evaluate proteinuria as risk factor for kidney graft survival in multimodal models taking into account renal function and other main clinical variables
♧ Methods:
▪︎This study investigated the impact of post transplant proteinuria in the first year in 1127 kidney transplants analyzing the impact of different donor ages. Proteinuria cut off was set at 0.5 g/day.
♧ Results:
▪︎Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age groups. Also, 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old (p < 0.05; Odd Ratio 1.8).
▪︎1-year graft function (eGFR < or ≥ 44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure. Low-grade proteinuria (0.2–0.5 g/day) demonstrated a trend for worse graft survival with increasing donor age. Also in kidney-paired analysis proteinuria ≥0.5 effect was more significant with donors > 50 years old.
♧ Conclusions:
▪︎This study clearly
evidence that proteinuria is always deleterious to transplant outcome even at early follow up time point.
▪︎Post-transplant proteinuria was increasingly harmful with older donor age. ▪︎Proteinuria ≥0.5 g/day
correlates with worse outcomes in all transplanted patients. ▪︎Prognostic value of proteinuria and eGFR for graft and patient survival was comparable and these two variables remain significant risk factors even in a multivariate model that take into consideration the most important clinical variables (donor age, rejection, delayed graft function and
CMV viremia among others
Dealing with immunologic “low-risk” patients, where utility of protocol biopsy is still debated, the presence of proteinuria in the first year at a relatively low extent (0.5 g/day), even in the absence of donor specific antibodies, should suggesta careful evaluation of patients leading to for-cause biopsy.
▪︎Utility of protocol biopsy in patients with nonstandard donor, even in the absence of risk factors,
should be ascertained by further studies.
♧ Level of evidence: III
♧In our practice: We haven’t deceased donation yet in our country. In case of old donors ages we follow them regularly every month for 3 months in the then every 2 months within the first year with RFT and urine analysis. If there any evidence of proteinuria then ACR , 24 hour urine proteins are required or even a renal biopsy is performed
That is an excellent reply Dr Ashmaig,
It is an observational retrospective cohort study.
I would call it level 2 rather than level 3.
If it were case-control study then it would be called level 3. I am well aware that care-control studies have been kept with retrospective cohort by many thinkers.
1a:Systematic review (with homogeneity) of inception cohort studies; or a clinical decision rule validated in different populations.
1b:Individual inception cohort study with > 80% follow-up; or a clinical decision rule validated on a single population
1c:All or none case-series
2a:Systematic review (with homogeneity) of either retrospective cohort studies or untreated control groups in randomized controlled trials.
2b:Retrospective cohort study or follow-up of untreated control patients in a randomized controlled trial; or derivation of a clinical decision rule or validated on split-sample only
2c:”Outcomes” research
3a:Systematic review (with homogeneity) of case-control studies
3b:Individual case-control study
4:Case-series (and poor quality prognostic cohort studies)
5:Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”
OK . Thanks Prof
Aim of the study:
Methods:
Design: a retrospective observational cohort study.
Setting: Turin University Renal Transplant Center.
Duration: ” from January 2003 to December 2013.
population: 1127 deceased donor kidney transplants.
Ethical approval: approved by the local ethics committee (ethics committee of “Azienda Ospedaliera Universitaria Città Della Salute e Della Scienza di Torino”/the University of Turin).
Exclusion criteria: multi-organ grafts.
Data were collected from patients’ individual charts:
creatinine and proteinuria (in 24-h urine collections) were assessed at discharge, at 3, 6 months and 1, 2 and 5 years after transplantation. The proteinuria cut-off was set at 0.5 g/day.
eGFR was estimated by the CKD-EPI equation.
Pre-transplant donor biopsies were performed on the basis of a multidimensional assessment, including macroscopic appearance, renal function, donor comorbidities and echographic characteristics.
Post-transplant renal biopsies were performed for cause.
Patients were divided into 3 groups according to donor age: group A (< 50 years), group B (50–69 years), and group C ≥ 70 years.
The outcomes were analyzed for patients with at least 1 year of follow-up according to 1-year post-KT extent.
Results:
Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcomes in all donor age groups.
In addition, a 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old.
1-year graft function (eGFR < or ≥ 44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure.
Low-grade proteinuria (0.2–0.5 g/day) demonstrated a trend for worse graft survival with increasing donor age.
In kidney-paired analysis, proteinuria ≥0.5 effect was more significant with donors > 50 years old.
Conclusion:
Post-transplant proteinuria was increasingly harmful with older donor age.
Proteinuria ≥0.5 g/day correlates with worse outcomes in all transplanted patients. Prognostic value of proteinuria and eGFR for graft and patient survival was comparable and these two variables remain significant risk factors even in a multivariate model that takes into consideration the most important clinical variables (donor age, rejection, delayed graft function and cytomegalovirus viremia, among others).
Level 3 (retrospective observational cohort study)
In my country, we have only a living donation program.
That is an excellent reply Dr Huda,
It is an observational retrospective cohort study, as you state.
I would call it level 2 rather than level 3. If it were case-control study then it would be called level 3. I am well aware that care-control studies have been kept with retrospective cohort by many thinkers.
1a:Systematic review (with homogeneity) of inception cohort studies; or a clinical decision rule validated in different populations.
1b:Individual inception cohort study with > 80% follow-up; or a clinical decision rule validated on a single population
1c:All or none case-series
2a:Systematic review (with homogeneity) of either retrospective cohort studies or untreated control groups in randomized controlled trials.
2b:Retrospective cohort study or follow-up of untreated control patients in a randomized controlled trial; or derivation of a clinical decision rule or validated on split-sample only
2c:”Outcomes” research
3a:Systematic review (with homogeneity) of case-control studies
3b:Individual case-control study
4:Case-series (and poor quality prognostic cohort studies)
5:Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”
thank you
Please summarise this article in your own words
Introduction
Proteinuria is an independent risk factor
for CVD & mortality in native kidneys. It is also an indicator of graft damage & predicts allograft loss after KT.
Measuring proteinuria between 3 months & 1 year post-KT will help to detect ongoing damage & to adopt strategies to prevent further progression.
The study
Aim:
·To analyze the impact of different grades of 1-year proteinuria on patient & graft survival in KT from different donor ages.
·To evaluate the correlation between proteinuria & donor or recipient risk factors with graft loss.
·To evaluate proteinuria as risk factor for kidney graft survival in multimodal models.
Study design
·A retrospective observational cohort study of all deceased donor grafts done at one center from Jan 2003 to Dec 2013.
·Multi-organ grafts were excluded (to make study population homogenous & without confounders).
·The remaining 1127 consecutive KTs were analyzed.
·IS regimen mostly adopted were:
Induction with steroid boluses (rapidly tapered to 20 mg/day prednisone) & 2 doses of anti-CD25 Ab.
ATG for high immunological risk (e.g. prior transplant lost for AR, high PRA).
·Maintenance IS:CNI, MMF or Azathioprine & prednisone.
·MTORi (+/-low doses CNI), used in certain cases (malignancies, CNI intolerance, severe CNI toxicity).
Data collected from patients’ charts: creatinine & proteinuria (24) assessed at discharge, at 3, 6 months & at 1, 2 & 5 years after transplantation.
eGFR by CKD-EPI equation.
Pre-transplant donor biopsies:
-Not done in donors < 50 years
-Always done in donors >70 years.
-For donors 50–70 decision based on many factors including cerebrovascular cause of death, renal cortex thickness, renal diameters, diameter discrepancy between the 2 kidneys, donor HTN, donor DM, donor active smoking, & donor proteinuria > 100 mg/dl at urinalysis.
Post-TX biopsies: done for cause (a rise in creat ≥20% or proteinuria > of 0.5–1 g/day).
Patients were divided in 3 groups according to donor age:
·Group A (< 50 years):339 patients
·Group B (50–69 years): 496 patients
·Group C ≥ 70 years: 292 patients
Main outcomes were DCGS & patient survival.
Graft function & the relevant post-KT complications were also analyzed.
Statistical methods
Different methods used for percentages & analysis of variables.
Results
Mean follow-up was 8.21 years.
With 0.5 g/day as proteinuria cut-off, the association of 1-year proteinuria with DCGS & graft survival was seen in all donor age classes.
Impact of proteinuria on patient survival noted only for younger donors.
Donor age increased the degree of proteinuria impact: DCGS of patients with donor age ≥ 70 & higher 1-year proteinuria was only 29.7% versus 72.3% in recipients of kidneys from younger donors with the same proteinuria.
Median value of proteinuria population was 0.2 g/day
Impact of low grade proteinuria (0.2–0.5 g/day) compared with proteinuria < 0.2 g/day:
In the low grade proteinuria group there was no significant association of 1-year proteinuria with patient & graft survival & DCGS at any donor age.
Patients with increase in 6 month-1 year proteinuria >0.1 g/day had lower DCGS compared with patients with lower increase (10-year graft survival 69.9% vs 90.2%); this difference was confirmed irrespective to donor age.
Early adverse events (1st post KT year) were evaluated in the different proteinuria sub-groups:
-1-year post-KT proteinuria > 0.5 g/ day was associated with NODAT, GN & rejection.
-Transplant urologic complications & CMV viremia are association with proteinuria.
-Biopsies were more frequent in patients with higher 1 year proteinuria.
1-year eGFR evaluated to compare proteinuria & creatinine impact on graft survival: 1-year eGFR was strongly associated to patient, graft & DCGS.
A multivariate model analysis: 1-year proteinuria ≥ 0.5 g/day, donor age ≥ 70 years, 1-year eGFR < 44ml/ min & the onset of CMV viremia in the 1styear were independently associated with DCGS.
Discussion
Albuminuria (> 300 mg/day) was included in 2012 KDIGO because higher levels are associated with the risk of adverse outcomes (mortality, progression to ESRD).
A faster rate of CKD due to marked albuminuria (> 300 mg/day) was confirmed in patients with diabetic & non-diabetic renal diseases.
The adverse impact of proteinuria, at early post-KT time, on long-term outcome was was reported in several previous studies.
However, there was no agreement on definition of post-KT harmful proteinuria as well as post-KT considered time points.
Risk factors related to post-KT proteinuria attempted in several studies included:
-DGF greater
-BMI at transplant
-Older = donor age
-Greater HLA mismatch
-Tacrolimus use
– Antihypertensive use
This study showed:
-Proteinuria ≥0.5 g/day at the 1stpost transplant year significantly affected graft & patient survival.
-A synergic effect of proteinuria ≥0.5 g/day & donor age ≥ 70 years on DCGS.
– An association (a trend, not significant) between DCGS & low-grade PTO (≥ 0.2 < 0.5 g/day) in kidneys from donors above 70 years.
-Any variation of proteinuria between 6 months & 1 year post-KT had a worse graft outcome when donor age was ≥60.
-Proteinuria was also related to factors other than donor age, such as : pretransplant DM & glomerular Karpinsky score; NODAT & GN were associated with higher 1-year PTO surprisingly with similar distribution between donor age groups.
-Strong correlation between infection & rejection rates, especially when donor age was > 50 years.
-1-year proteinuria ≥0.5 g/day is comparable to CKD-EPI < 44 ml/min in predicting graft failure; donor age ≥ 70 make this association even worse.
-CMV viremia post-transplant was an independent predictor of DCGS.
-Majority of organs are from “suboptimal” donors (ECD or KPI>85%); prognostic significance of proteinuria was particularly seen with this kind of donors.
-Benefit for ACEi/ARB use in TX recipients is lacking; they reduce proteinuria without improvement of patient or allograft survival as in non-transplant patients such as in diabetic nephropathy.
Strengths:
Homogeneous & relatively large population
Long term follow up.
Validation of prognostic impact of proteinuria in a subset of paired kidneys (limiting donor-derived confounding factors).
Limitations
Absence of protocol biopsies for center policy; however, some authors report that proteinuria impact is independent from the underlying allograft histology.
Absence of routinely evaluating DSA in the 1styear; so, evaluation under this aspect.
Lack of qualitative differentiation of urinary protein (tubular or glomerular proteinuria could have differently impact graft outcome).
Conclusions
Proteinuria is always deleterious to the graft outcome even at early follow up time point.
Close monitoring of proteinuria should be done repeatedly especially in the case of elderly donors.
Consider biopsy with low grade proteinuria (0.5 g/day) in the 1styear even if no DSA.
Use of protocol biopsy in patients with non-standard donor needs to be ascertained.
=======================
What is the level of evidence provided by this article?
Level III, retrospective cohort study
=======================
Please reflect on the guidelines and refer to your practice.
Despite the relatively large population, however, this is a retrospective single center study. There is a need for large multicenter studies to validate the results.
The study included only deceased donor transplantation. The results might not be extrapolated to living donor transplants; in our center, as well as in our country, we perform only living donor kidney transplants.
That is excellent reply, dear Dr Mohamed.
It is an observational retrospective cohort study, as you state.
I would call it level 2 rather than level 3. If it were case-control study then it would be called level 3. I am well aware that care-control studies have been kept with retrospective cohort by many thinkers.
1a:Systematic review (with homogeneity) of inception cohort studies; or a clinical decision rule validated in different populations.
1b:Individual inception cohort study with > 80% follow-up; or a clinical decision rule validated on a single population
1c:All or none case-series
2a:Systematic review (with homogeneity) of either retrospective cohort studies or untreated control groups in randomized controlled trials.
2b:Retrospective cohort study or follow-up of untreated control patients in a randomized controlled trial; or derivation of a clinical decision rule or validated on split-sample only
2c:”Outcomes” research
3a:Systematic review (with homogeneity) of case-control studies
3b:Individual case-control study
4:Case-series (and poor quality prognostic cohort studies)
5:Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”
1- Summary of this article :The optimal time of measure proteinuria to detect ongoing damage and to prevent its progression is between 3 month and one year post KT.
Aim of this study was to analyse the impact of different degrees of 1-year proteinuria an patient and graft survival in Kidney transplants from different donor ages and to evaluate the correlation between proteinuria and donor or recipient risk factors with graft loss.
To evaluate proteinuria as risk factor for kidney graft survival.
Methods
Retrospective observational cohort study performed at Turin University Renal transplant centre from Jan 2003 to Dec 2013.
The recipient’s follow up was performed with scheduled clinical visits for follow up.
Data collected from patients individual charts creative and proteinuria at discharge at 3,6 month and 1,2 and 5 years after transplantation.
eGFR for Renal allograft function, pre-Transplant donor biopsies were preformed on the basis.
Assessment Results
The analysis included 1127 Kidney recipients transplant
Selected population depend on donor age
Group A < 50 years old
Included 339 patients
Group B 50-69 yrs old including 496 patient
Group C > 70 yrs old including 292 patients
Younger age . all donors the proteinuria impact on their survival
6- I year proteinuria increase was not assaulted with patient survival at any donor age.
Associated with poor graft survival.
I-year post KT proteinuria > 0-5 gml day was associated with new an set Dmg GN and rejection comparison of post-KT complication between the two groups confirmed a statistically higher rate of rejection and GN and greater number of biopsies in the groups with I-year PTO > 0-5 glday.
No significant variation between the groups for the others analysed variables.
Discussion
DM and Dm with Albumimnia > 300mg I day. Is associated with a faster rate of CKD progression
Risk Factors related to post KT proteinuria included donor related, recipient related or transplant related factors such as delay graft function, high BMI at TX, older age greater HLA is match, TAC a sec and anti HTN use.
Study showed that I-year proteinuria >= 0.5 glday compared to CKD – EPIC < 44mL/min in predicting graft function by multivariate analysis.
Donor age >= 70 years make this association even worse
CMV viremia post-transplant result in independent predictor of DCGS in multivariate analysis.
Strength of this Study:-
Large sample size
Validation of prognostic impact of proteinuria in a subset of pained Kidneys
Limitation of this Study
DSA evaluation test not exists in the first year
Lack of qualitative differentation of urinary protein, considering that tubular and glomerular proteinuria have different impact on graft outcome conclusion
Single non invasive biomarker will not has a high predictive performance for graft loss.
Post KT proteinuria with clinical measures
Donor elderly, other causes of proteinuria are excluded ( infection metabolic disease).
2- level of evidence is retrospective study level 3
3-we screen our pateints for protinurea every 3 month for 1 year.
That is excellent reply, dear Dr Manal Malik.
It is an observational retrospective cohort study, as you state.
I would call it level 2 rather than level 3. If it were case-control study then it would be called level 3. I am well aware that care-control studies have been kept with retrospective cohort by many thinkers.
1a:Systematic review (with homogeneity) of inception cohort studies; or a clinical decision rule validated in different populations.
1b:Individual inception cohort study with > 80% follow-up; or a clinical decision rule validated on a single population
1c:All or none case-series
2a:Systematic review (with homogeneity) of either retrospective cohort studies or untreated control groups in randomized controlled trials.
2b:Retrospective cohort study or follow-up of untreated control patients in a randomized controlled trial; or derivation of a clinical decision rule or validated on split-sample only
2c:”Outcomes” research
3a:Systematic review (with homogeneity) of case-control studies
3b:Individual case-control study
4:Case-series (and poor quality prognostic cohort studies)
5:Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”
Please summarise this article in your own words
proteinuria is well known marker for worse renal outcome and patient survival, this issue also true for transplanted kidneys, this study highlights the donor variables that affect the recipients survival and renal outcomes, with and without proteinuria.
Study design:
Retrospective observational cohort study, in Turin university hospital , including 1127 deceased donor kidney transplants performed, during the period from 2003-2013, under went same evaluation process by the same transplant team, the donors subclassifed according to their age< 50 yrs, 50-69 yrs or more than 70 yrs, kapinsky score was used for single, dual kidney transplant, or refusal of the kidney, with written consent taken from patients to collect the data.
Primary outcomes:
Death censored graft survival(DCGS), 6 month and 1- year post transplant proteinuria, and patient survival.
Results:
= Donor age increase the risk of proteinuria – older tend to has more proteinuria.
= The patient’s survival was worse among the younger donors age group.
= DCGS in donors age >70 yrs of age and higher proteinuria was less than those young donors’ with the same proteinuria(P= 0.03).
= Proteinuria per se was not significantly related to 1- year PTO, graft survival and DCGS atany donor age
= No correlation between total Karpinsky score and DCGS in any of group analyzed.
= Angiotensin Converting Enzyme inhibitors/ Angiotensin II Receptor Blockers (ACEi/ARB) therapy did not influence 6mo-1 yr proteinuria variations.
= proteinuria impact (≥ 0.5 g/day) was not associated with significant variation in DCGS in the different age groups.
= 1-year post-KT proteinuria > 0.5 g/day was associated with new onset diabetes (NODAT), glomerulonephritis, rejection, transplant urologic complications and Cytomegalovirus (CMV) viremia.
= eGFR was strongly associated to patient, graft and DCGS (p < 0.01).
= There were higher rate of rejec[1]tion and glomerulonephritis and greater number of biopsies in the group with 1-year PTO ≥ 0.5 g/day.
= Infections and CMV viremia as well as vascular and urological complications were, on the contrary, significantly more frequent in older donor population.
Strength:
Large number patient data all examined by the same team and underwent the same criteria of selection.
The validation of prognostic impact of proteinuria in a subset of paired kidneys, limiting undetermined donor-derived confounding factor.
Limitations:
Absence of protocol graft biopsies for center policy.
Absence of routinely donor specific antibody evaluation in the first year, which has a major impact on proteinuria and graft survival.
Lack of qualitative differentiation of urinary protein, considering that tubular or glomerular proteinuria could have different impact on graft outcome,
Conclusion:
Proteinuria is a marker of damage progression and established loss of renal function, thus require more intense follow up.
Rejections, number of biopsies, NODAT and glomerulonephritis were associated with higher 1-year PTO.
Proteinuria in the first year at a relatively low extent (0.5 g/day), even in the absence of donor specific antibodies, needs a careful evaluation of patients leading to for-cause biopsy.
What is the level of evidence provided by this article?
Level of evidence II
Please reflect on the guidelines and refer to your practice.
In our practice we usually not accepting older donors specialy those more than 60 years of age, we use to follow urinary protein by spot urine for protein/creatinine ratio test, as it is an isolated factor for graft loss, disease recurrence, occurrence of NODAT….etc, by the guidelines given by this study we better understand the impact of proteinuria, and will make us more comfortable dealing with it.
That is excellent reply, dear Dr Mohamed.
It is an observational retrospective cohort study, as you state. Why do you label it as level 2?
1a:Systematic review (with homogeneity) of inception cohort studies; or a clinical decision rule validated in different populations.
1b:Individual inception cohort study with > 80% follow-up; or a clinical decision rule validated on a single population
1c:All or none case-series
2a:Systematic review (with homogeneity) of either retrospective cohort studies or untreated control groups in randomized controlled trials.
2b:Retrospective cohort study or follow-up of untreated control patients in a randomized controlled trial; or derivation of a clinical decision rule or validated on split-sample only
2c:”Outcomes” research
3a:Systematic review (with homogeneity) of case-control studies
3b:Individual case-control study
4:Case-series (and poor quality prognostic cohort studies)
5:Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”
Yes, it is Level III
Thank you
Proteinuria is known to be an independent risk factor for cardiovascular disease and mortality in native kidneys as well as an indicator of renal damage and a predictor of allograft loss after kidney transplantation.
Aim of this study: Analyze the impact of different degrees of 1-year proteinuria on patient and graft survival in kidney transplants from different donor ages and to evaluate the correlation between proteinuria and donor or recipient risk factors with graft loss.
Secondary aim: Evaluate proteinuria as risk factor for kidney graft survival in multimodal models taking into account renal function and other main clinical variables.
Method:
Study design: retrospective observational cohort study
Study period: from January 2003 to December 2013
Inclusion: all deceased donor grafts performed at one transplant center
Excluded multiorgan grafts analyzing the remaining 1127 consecutive kidney transplants (KT).
Collected data:
– Creatinine and proteinuria (24-h urine) were assessed at discharge, at 3, 6 months and at 1, 2 and 5 years
– eGFR was estimated CKD-EPI equation.
– Pre-transplant donor biopsies; always if donor age > 70 years, in age < 50 usually not done, 50-70 years depend os the assessment of comorbidities and renal function.
– Post-transplant renal biopsies were performed if creat. ≥20% of baseline value or proteinuria > of 0.5–1 g/day).
– Follow-up ended on November 2017.
– The outcomes were analyzed for patients with at least 1 year of follow-up according to 1-year post-KT extent.
– Proteinuria values after the sixth post-KT month explored; to eliminate confounding factors, as native
kidneys proteinuria.
– 1-year PTO used a cut-off 0.5 g/ day.
– Paired kidney analysis was performed considering only cases where both kidneys from the same deceased donor were transplanted at our institution (370 recipients, 185 pairs).
Results:
The population was classified by donor age: group A < 50, group B 50–69, group C >70 years old.
Mean follow-up was 8.21 years.
Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age
groups.
Donor age increased the magnitude of proteinuria impact: DCGS of patients with donor age ≥ 70 years and higher 1-year PTO was only 29.7% versus 72.3% in recipients of kidneys from younger donors with the same proteinuria.
The low grade proteinuria did not show any significant association of 1-year PTO with patient and graft survival and DCGS at any donor age. demonstrated a trend for worse graft survival with increasing donor age.
6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old.
1-year post-KT proteinuria > 0.5 g/day was associated with new onset diabetes (NODAT), GN and rejection.
1-year graft function (eGFR < or ≥ 44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure (Hazard Ratio 2.77 vs Hazard Ratio 2.46).
In this multivariate analysis;1-year PTO ≥ 0.5 g/day, donor age ≥ 70 years, 1-year eGFR < 44ml/ min and the onset of CMV viremia in the first year were independently associated with DCGS. Rejection was a significant variable only when considered in the entire follow-up (not when 1st year rejections were considered).
Also in kidney-paired analysis proteinuria ≥0.5 effect was more significant with donors > 50 years old (OR 2.3).
Strengths:
– Homogeneity of the population.
– Patients were centrally followed in the long term with all data recorded in patients’ charts.
– The validation of prognostic impact of proteinuria in a subset of paired kidneys, thus limiting confounding factors.
Limitations:
– Absence of protocol graft biopsies, this limitation reduces its importance when we consider that proteinuria impact was shown by some authors to be independent from the underlying renal allograft histology.
– Absence of routinely DSA evaluation in the first year, available only in a minority of patients.
– Lack of qualitative differentiation of urinary protein, considering that tubular or glomerular proteinuria.
Level 3, retrospective observational cohort study.
Proteinuria monitoring every 1 month initially then every 3 months and if clinically indicated.
Old for old policy considering the morbidity and the expected life span .
That is excellent reply, dear Dr Hadeel.
It is an observational retrospective cohort study, as you state.
I would call it level 2 rather than level 3. If it were case-control study then it would be called level 3. I am well aware that care-control studies have been kept with retrospective cohort by many thinkers.
1a:Systematic review (with homogeneity) of inception cohort studies; or a clinical decision rule validated in different populations.
1b:Individual inception cohort study with > 80% follow-up; or a clinical decision rule validated on a single population
1c:All or none case-series
2a:Systematic review (with homogeneity) of either retrospective cohort studies or untreated control groups in randomized controlled trials.
2b:Retrospective cohort study or follow-up of untreated control patients in a randomized controlled trial; or derivation of a clinical decision rule or validated on split-sample only
2c:”Outcomes” research
3a:Systematic review (with homogeneity) of case-control studies
3b:Individual case-control study
4:Case-series (and poor quality prognostic cohort studies)
5:Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”
2.Please reflect on the guidelines and refer to your practice.
That is excellent reply, dear Dr Mohamed.
It is an observational retrospective cohort study, as you state. Why do you label it as level 2?
proteinuria shown to be an independent risk factor for mortality and cardiovascular disease in both native and deceased kidneys.
As early as possible detection of proteinuria give a chance of early treatment and control and hence delay or prevent kidney damage and disease progression.
The direct association between older donors and early proteinuria is not well studied, moreover most studies have been used a far young ages ( average 45 years).
Methods:
Results;
Discussion;
Strength of the study;
Limitations:
Conclusion:
Multifactor were affect graft survival, not a single biomarker.
Proteinuria is always can affect graft survival even at early follow up time .
Close monitoring of proteinuria should be done routinely
Further studies needed to be done for utility of protocol biopsy.
proteinuria in older kidney donor was harmfully affected by proteinuria
Proteinuria >0.5 g/d associated with worse outcome in all transplant patients.
Level of evidence :
Level ((II)) cohort study.
Reflection of study result on my facility:
considering the risk of proteinuria as associated with worse outcome and graft survival
considering proteinuria in older age donors
considering other risk factors causing proteinuria in post KT
Thank you
It is a retrospective observational study (level 3)
Thank you prof.
#Please summarise this article in your own words
#The objective:
*To assess the result of different degrees of 1-year proteinuria on recipient and graft out come in kidney transplants from different donor ages.
*To analyze the correlation between proteinuria and donor or recipient risk factors with graft loss.
* To estimate proteinuria as risk factor for kidney graft survival in multimodal models, taking into account renal function and other main clinical variables.
# Summary:
*Proteinuria is known to be an independent risk factor for CVD and mortality in native kidneys, also it is pointer for renal damage and PTK loss. However the significance of proteinuria related to patient and graft survival and its correlation with donor and recipient characteristics are poorly investigate.
*Halimi and coworkers conducted that there is strong correlation of 1- and 3-month proteinuria (per every 0.1 g/day increase) with graft loss, while Amer and colleagues analyzed 1-year post KT proteinuria finding an Hazard Ratio (HR) for graft loss of 2.15, associated with proteinuria between 150 and 500 mg/day and an HR of 5.11 with higher level of proteinuria.
*Recently Naesens et al found a strong direct assossation between 1-year post KT proteinuria and graft loss irrespectively from graft histology, but only for proteinuria
values higher than 1 g/day (HR 2.17).
* Other study by Cantarovich and coworkers, proteinuria > 0.5 g/ d, at 3-month and 2 year post-KT was a significant prognostic marker of graft outcome. At 5-years, this significance was not observed.
#Methods:
*Retrospective observational cohort study including all deceased donor grafts performed at Turin University Renal Transplant Center “A. Vercellone” from January 2003 to December 2013.
*The study was submitted and approved by the local ethics committee (ethics committee of “Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino”/ University of Turin)
* It was investigated the effect of post transplant proteinuria in the first year in 1127 kidney transplants analyzing the impact of different donor ages. Proteinuria cut off was set at 0.5 g/day.
*The Immunosuppressive regimen differed according to different transplantation eras and different populations.
*Data were collected from patients’ individual charts: creatinine and proteinuria (in 24-h urine collections) were assessed at discharge, at 3, 6 months and at 1, 2 and 5 years after transplantation.
*Patients were divided in 3 groups according to donor age: group A (< 50 years), group B (50–69 years), group C ≥ 70 years.
*The (eGFR) was estimated by (CKD-EPI) equation.
*The piopsy is usually performed in donors older than 70 years. For donors with age 50–70 several characteristics are taken into consideration .
The proteinuria values follow after the sixth post-KT month; when comparing
6-month and 1-year proteinuria (1-year PTO), the latter showed a better correlation with death censored graft survival (DCGS).
#Results:
*Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age groups.
*The 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old (p < 0.05; Odd Ratio 1.8). 1-year graft function (eGFR < or ≥ 44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure (Hazard Ratio 2.77 vs Hazard Ratio 2.46).
* Low-grade proteinuria (0.2–0.5 g/day) demonstrated a trend for worse graft survival with increasing donor age.
*In kidney-paired analysis proteinuria ≥0.5 effect was more significant with donors > 50 years old.
#Strenghts of the study:
*Related to homogeneity of the population, characterized by a wide range of data coming from over a thousand of KTs performed with the same team.
*Patients were centrally followed in the long term with alldata recorded in patients’ charts.
*Validation of prognostic impact of proteinuria in a subset of paired kidneys, thus limiting undetermined donor-derived confounding factors.
# Limitation of this study:
*Absence of protocol graft biopsies for center policy.
*Absence of routinely donor specific antibody evaluation in the first year.
*Lack of qualitative differentiation of urinary protein.
#Conclusions
Post-transplant proteinuria was increasingly harmful with older donor age. Proteinuria ≥0.5 g/day correlates with worse outcomes in all transplanted patients. Prognostic value of proteinuria and eGFR for graft and patient survival was comparable and these two variables remain significant risk factors even in a multivariate model that take into consideration the most important clinical variables (donor age, rejection, delayed graft function and cytomegalovirus viremia among others).
# What is the level of evidence provided by this article?
*It is retrospective observational cohort study level 3.
# Please reflect on the guidelines and refer to your practice.
*We don’t have deceased donation in our country, but in case of old donors we follow up the patient regularly every month for 3 months then every 2 months with RFT and urine analysis if there any possibility of proteinuria we do ACR, 24 hour urine protein and we can go further to renal biopsy.
Thank you
Please summarise this article in your own words :
1- proteinuria equal to or more than 0.5 g/day is always deleterious to transplant outcome including patient and graft survivals, even at early follow up time point.
2- 6 month to 1 year post-transplant proteinuria was significantly associated with poor graft outcome especially if donors were 60 years old or older. therefore, close monitoring of proteinuria should be repeatedly performed in cases of elderly donors.
3- low grade proteinuria of 0.2-0.5 g/day demonstrated a trend for worse graft survival with increasing donor age.
What is the level of evidence provided by this article?
Please reflect on the guidelines and refer to your practice :
Thank you
Please summarise this article in your own words
Introduction
According to several studies, the optimal timing for measuring proteinuria to detect ongoing damage is between 3months and one year post-KT
Most previous studies showed a strong correlation of early post-transplant proteinuria with graft loss (only one study used Extended Criteria Donors)
This was the first study to address the impact of proteinuria on KTs from different donor age classes
Aim of the study
1. Addressing the impact of post transplant proteinuria in the first year on patient and graft survival in kidney transplants from different donor ages and to evaluate the correlation between proteinuria and donor or recipient risk factors with graft loss
2. Evaluate proteinuria as risk factor for kidney graft survival in multimodal models taking into account renal function and other main clinical variables
Methods
All deceased donor grafts were included in one center (Turin University Renal Transplant Center) from January 2003 to December 2013
Creatinine and proteinuria (in 24-h urine collections) were assessed at discharge, at 3, 6months and at 1, 2 and 5years after transplantation (proteinuria cut-off was 0.5g/day)
Pre-transplant donor biopsies were performed on the basis of a multidimensional assessment including macroscopic appearance, renal function, donor comorbidities and echographic characteristics (usually not performed in donors <50years and always performed in donors older than 70years, for donors with age 50–70 several characteristics are taken into consideration including donor CVA cause of death in the absence of vascular malformation, echographic parameters, donor HTN, donor DM, donor active smoking, donor proteinuria >100mg/dl at urinalysis)
Post-transplant renal biopsies were performed when serum Creatinine increased ≥20% of baseline value or with proteinuria > of 0.5–1g/day
Results
The study included 1127 kidney recipients, transplanted at Turin University Renal Transplant Center (between January 2003 and December 2013)
Patients were divided in 3 groups according to donor age: group A (<50years), group B (50–69years), group C≥70years
Association of 1-year proteinuria with DCGS and graft survival was present for all donor age
Six month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors >60years
1-year graft function (eGFR < or≥44ml/min) had similar impact to proteinuria (≥ 0.5g/day) on graft failure
Discussion
This was the first study to address the impact of proteinuria on KTs from different donor age classes
The study demonstrated that proteinuria (≥ 0.5g/day) at the first post-transplant year, was significantly linked to graft survival and patient survival
Very low grade proteinuria (0.2 and 0.5g/ day) was not related to outcome. Only in kidneys from donors older than 70years old there is an association between deaths censored graft survival (DCGS) and low-grade proteinuria
Older donor kidneys were more sensitive to proteinuric injuries when compared with younger ones (worse graft outcome when donor age was ≥60years)
Strength of the study
1. Homogeneity of the population (wide range of data coming from over a thousand of KTs)
2. Long term duration with all data recorded in patients’ charts
3. Validation of prognostic impact of proteinuria in a subset of paired kidneys
Limitations of the study
1. Absence of protocol graft biopsies
2. Absence of routinely donor specific antibody evaluation in the first year
3. Lack of qualitative differentiation of urinary protein ( tubular or glomerular) because they could have different impact on graft outcome
Conclusion
Proteinuria is always deleterious to transplant outcome and more with older donor age
Close monitoring of proteinuria should be performed especially for elderly donors
In low-risk immunologic patients, the presence of proteinuria in the first year at a relatively low extent (0.5g/day), even in the absence of DSA, should suggest a careful evaluation of patients (biopsy)
Further studies are needed regarding the utility of protocol biopsy in patients with non-standard donor, even in the absence of risk factors
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
Post-transplant, we do albumin/creatinine ratio 3 months, 6 months and one year and if indicated at any time
Thank you
It is a retrospective observational study (level 3).
Thank you Prof.
Summary:
Proteinuria after kidney transplantation may cause a worse graft survival. Proteinuria is an independent risk factor for CV mortality in patents with CKD. Post-kidney transplant, it has also been shown to reduce allograft survival.
This study investigated the impact of post transplant proteinuria in the first year in 1127 kidney transplants and analyzed the impact of different donor ages. Recipients were divided in to 3 cohorts based on donor age. Less than 50 years (339 patients), 50 – 69 years (496 patients), > 70 years (292 patients)
Proteinuria cut off was set at 0.5 g/day. Results: Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age groups. In addition, 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old (p < 0.05; Odd Ratio 1.8). 1-year graft function (eGFR < or ≥ 44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure (Hazard Ratio 2.77 vs Hazard Ratio 2.46). Low-grade proteinuria (0.2–0.5 g/day) demonstrated a trend for worse graft survival with increasing donor age. Also in kidney-paired analysis proteinuria ≥0.5 effect was more significant with donors > 50 years old (Odd Ratio 2.3).
Post-transplant proteinuria was increasingly harmful with older donor age. Proteinuria ≥0.5 g/day correlates with worse outcomes in all transplanted patients. Proteinuria causes a worse outcome especially in donors more than 60 years of age.
Level of evidence: level 4.
Practice in my center: from now on I’ll follow up my patients according to this study.
Thank you
It is a retrospective observational study (level 3).
The aim o the study ;
Primary aim;
1-to analyze the impact of different degrees of 1-year proteinuria on patient and graft survival in kidney transplants from different donor ages.
2- to evaluate the correlation between proteinuria and donor or recipient risk factors with graft loss.
Secondary aim;
1- to evaluate proteinuria as risk factor for kidney graft survival in multimodal models taking into account renal function and other main clinical variables.
The type o the study ;
a retrospective observational cohort study
The study area ;
Turin University Renal Transplant Center “A. Vercellone”
Ethical approval;
approved by the local ethics committee (ethics committee of “Azienda Ospedaliera Uni-
versitaria Città della Salute e della Scienza di Torino”/ University of Turin).
Population;
1127 kidney transplants .
Method ;
This study investigated the impact of post transplant proteinuria in the first year in 1127 kidney transplants analyzing the impact of different donor ages. Proteinuria cut off was set at 0.5 g/day.
The result o the study ;
1-Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age groups. In addition, 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors .
2-1-year graft function (eGFR < or ≥ 44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure .
3-Low-grade proteinuria (0.2–0.5 g/day) demonstrated a trend for worse graft survival with increasing donor age.
4- in kidney-paired analysis proteinuria ≥0.5 effect was more significant with donors > 50 years old .
The Strenghts of the study are;
1-The homogeneity of the population .
2- The validation of prognostic impact of proteinuria in a subset of paired kidneys.
The limitations of this study ;
1-The absence of protocol graft biopsies for center policy.
2-The absence of routinely donor specific antibody evaluation in the first year
3-lack of qualitative differentiation of urinary protein,
Conclusion ;
1-Thestudy demonstrated that occurrence of proteinuria,(≥ 0.5 g/day), at the first post-transplant year, was significantly linked to graft survival and patient survival.
2-Older donor kidneys seemed more sensitive to proteinuric injuries in comparison with younger ones with very relevant differences of DCGS in different donor age classes with same proteinuria.
3-Proteinuria is, marker of damage progression and established loss of function, as witnessed by concordance between proteinuria grade and renal function in transplanted patients.
4-. 1-year proteinuria ≥0.5 g/day is comparable to CKD-EPI < 44 ml/min in predicting graft failure by multivariate analysis.
5-The study clearly evidence that proteinuria is always deleterious to trans-plant outcome even at early follow up time point.
What is the level of evidence provided by this article?
Level III
Please reflect on the guidelines and refer to your practice.
1-The study suggest that, in the context of elderly donors and in the absence of acknowledged effective pharmacological tools, when other causes of proteinuria are excluded (e.g. cardiovascular diseases, infections, metabolic comorbidities), close monitoring of proteinuria should be repeatedly performed.
2-Dealing with immunologic “low-risk” patients, where utility of protocol biopsy is still debated, the presence of proteinuria in the first year at a relatively low extent (0.5 g/day), even in the absence of donor specific antibodies, should suggest a careful evaluation of patients leading to for-cause biopsy.
3-Utility of protocol biopsy in patients with non- standard donor, even in the absence of risk factors, should be ascertained by further studies.
In my practice ;
Post kidney transplant ,we monitor protenuria every 3 months .
Thank you
It is a retrospective observational study (level 3).
it is a retrospective study conducted in Turin by reviewing medical records of 1127 transplanted recipients between the years 2003 and 2013.The cohort involved were those developed post transplant proteinuria which was defined as more than 500 mg per day. The target was to assess the eGFR and volume of proteinuria at 6 and 12 months post transplantation regardless to the underlying etiology , but according to the deceased donor age.verifying the impact of donors age on the incidence of proteinuria and eGFR post transplantation.
Features of the study:
The transplant protocol includes induction with CD25 antagonist Basiliximab 20 mg two doses, but those with higher immunologic risk [ High PRA, previous transplant rejection] were induced with ATG. Induction with Cs with maintenance prednisolon with swift tapering to 20 mg. Maintenance protocol include CNI , mainly Tacrolimus along with mycophenolate and prednisolon. mTOR was added to minimize or replace CNI in case of toxicity. importantly, the strategy of inducing CNI, entails delaying the commencement of the same until creatinine reached to 2.5 mg/dl. to belittle the incidence of delayed graft function.
The recipients were classified into 3 groups:
Group a : Donors of 50 year old or below .
Group B: 50-69 year old donors.
Group c : more than 70 year old.
proteinuria was checked regularly started 3 months post transplant.
The results of the study revealed the association of adverse renal outcome of proteinuria of more than 0.5 gm/day on the allograft survival in all transplant recipients with prominent impact on the elder donors kidneys ( more than 70 year old ). It was concluded that both of the parameters proteinuria and eGFR are mutually affecting the prognosis of the transplant recipients in an equivalent manner. This might be reflecting the burden of a compromized aged kidney of a 70 year old donors which is more prone to be damaged by reperfusion , ischemia, medication induced nephropathy and acute rejection ext.therefore the it would be more prominently injured by the consequences of hyperfiltration and intraglomerular hypertension.
Interestingly , the cardiovascular mortality was elevated with high rate of DCGS.
Thank you
Introduction
Older donors are being increasingly utilized to increase the donor pool and reduce the kidney transplant waiting times. Kidneys from older donors are more prone to non-specific injuries and have increased ischemia-reperfusion injuries and delayed graft function. However, the death censored graft survival (DCGS) is similar if correct allocation is done of the kidneys from older donors.
Proteinuria is an independent risk factor for CV mortality in patents with CKD. Post-kidney transplant, it has also been shown to reduce allograft survival. Several studies have speculated that the optimal time of checking for proteinuria is between 3 months and 1 year post-transplantation so that measures can be out in place to prevent its progression.
The impact of post-KT proteinuria on recipients of elderly donors has not been clearly defines and studied
Aim
The aim of this study was to analyze the impact of different degrees of 1 year proteinuria on patient and graft survival in Its from different donor ages and to evaluate the correlation between proteinuria and donor or recipient risk factors with graft loss.
A secondary aim was to evaluate proteinuria as a risk factor for kidney graft survival in multimodal models making in to account renal and other clinical variables
Methodology
This was a retrospective observational cohort study that looked at all the deceased donor grafts transplanted from January 2003 to December 2013. Multiorgan grafts transplanted were excluded from the study. 1127 kidney transplants were included in the study.
Induction therapy consisted of basiliximab for low risk patients and ATG for high risk patients. Maintenance immunosuppression regimens consisted of prednisone, CNIs and antimetabolite. mTOR inhibitors with or without low dose CNIs were used in selected cases. Analysis was done with and without mTOR inhibitor as mTORI have been known to cause proteinuria.
Data were collected from patients medical records: serum creatinine and 24 hour protein were assessed at discharge, 3 months, 6 months, 1 year, 2 years and 5 years post-transplantation. GFR was estimated using the CKD EPI equation. Pre-transplant biopsies were performed in all donor kidneys from donors more than 70 years. Pre-transplant biopsies were not performed if the donor was less than 50 years. For donors between 50 and 70 years, pre-transplant biopsy was only performed if there was an indication. Post-Transplant biopsies were performed if there was an increase of serum creatinine by at least 20% and or there was proteinuria of more than 0.5 gm/day.
Recipients were divided in to 3 cohorts based on donor age:
Outcomes were analyzed for patients with at least one year of follow up.
Proteinuria cut off was 0.5 gm/day. A lower cut off was also analyzed: 0.2 – 0.5 gm/day.
The main outcomes were:
Graft function and post kidney complications were also studied
Paired kidney analysis was also performed in cases where both kidneys from the same donor were transplanted in recipients at the study site
Results
Transplant proteinuria of > 0.5 gm/day was associated with poor graft and patient survival across all patient groups.
6 month to one year proteinuria of more than 0.5 gm/day was associated with a poor graft survival in recipients who had a kidneys from donor more than 60 years
In order to assess if other donor factors could be related to post-KT proteinuria, karpinsky score was evaluated when pre-transplant biopsies were available. Total karpinsky score as well as glomerulosclerosis score was not associated with DCDS differences
Patients with an increase in 6 month – 1 year proteinuria of more than 0.1 gm/day had a lower DCGS when compared to patients with a lower increase (10 year graft survival: 69.9% vs 90.2%, p < 0.01). This was irrespective of donor age.
Proteinuria of 0.2 – 0.5 gm/day was not associated with a significant reduction in graft and patient survival although it was trending towards that.
One year post KT proteinuria was associated with NODAT, glomerulonephritis and rejection.
Among 185 kidney pairs, DCGS was 86.6% for recipients with proteinuria < 0.5 gm/day and 51.9% for the twin kidney with proteinuria > 0.5 gm/day. This impact was greater in donors more than 50 years of age
Conclusion
Post-transplant proteinuria was associated with reduced patient and graft survival across all donor ages. Proteinuria portends a worse outcome especially in donors more than 60 years of age. It is imperative that recipients with older donor kidneys are followed up more closely and if proteinuria is detected, treated aggressively to improve patient and graft survival
Level of evidence:
The level of evidence is level 3. This was a retrospective cohort study. The sampling was consecutive sampling
Practice in my center
We don’t do deceased donation. However, post kidney transplant, recipients get a UACR done at three months, six months and one year. We don’t routinely do 24 urine protein due to convenience and cost
Thank you
Increase of donor pool by using elderly donors has been largely adopted to reduce kidney transplant (KT) waiting list. Proteinuria is known to be an independent risk factor for cardiovascular disease and mortality in native kidneys as well as an indicator of renal damage and a predictor of allograft loss after kidney transplantation. One study showed a strong correlation of 1- and 3-month proteinuria (per every 0.1 g/day increase) with graft loss. Another recent study found a strong direct correlation between 1-year post KT proteinuria and graft loss irrespectively from graft histology, but only for proteinuria values higher than 1 g/day.
This study investigated the impact of post transplant proteinuria in the first year in 1127 kidney transplants analyzing the impact of different donor ages.
Study design
– This is a retrospective observational cohort study including all deceased donor grafts performed at Turin University Renal Transplant Center from January 2003 to December 2013. 1127 consecutive kidney transplants were included in this study.
– Immunosuppressive regimen differed according to different transplantation eras and different populations.
– The recipients’ follow-up was performed with scheduled clinical visits for the entire follow-up and hospital admissions when major complications occurred.
– Data were collected from patients’ individual charts: creatinine and proteinuria (in 24-h urine collections) were assessed at discharge, at 3, 6 months and at 1, 2 and 5 years after transplantation.
– Mean follow-up was 8.21 years (25th–75th percentiles: 5.38–11.43 years).
Results
The selected population was classified by donor age: group A (less than 50 years old) including 339 patients, group B (50–69 years old) including 496 patients and group C (more than 70 years old, with a maximum age of 88 years) including 292 patients.
– With 0.5g/day cut off for proteinuria, 1 year PTO with DCGS, and graft survival was present in all age group and donor age increase the magnitude of proteinuria impact.
– The median value for proteinuria in the study was 0.2g/day.
– 6 months to 1 year proteinuria was not associated with patient survival in any donor age group.
– 1 year post transplant proteinuria was associated with NODAT, glomerulonephritis and rejection.
– CMV viremia with urological complication is also associated with proteinuria.
– Multivariate analysis of 1-year PTO ≥ 0.5 g/day, donor age ≥ 70 years, 1-year eGFR < 44 ml/ min and the onset of CMV viremia in the first year were independently associated with DCGS.
Type of study and level of evidence
Retrospective study , level of evidence 3
Thank you