Allograft Failure in Kidney Transplant Recipients With Membranoproliferative Glomerulonephritis

doi:10.1053/j.ajkd.2010.09.021

American Journal of Kidney Diseases

Volume 57, Issue 2, February 2011, Pages 291-299

https://doi.org/10.1053/j.ajkd.2010.09.021 Get rights and content

Background

Membranoproliferative glomerulonephritis types I (MPGN-I) and II (MPGN-II) are rare diseases that in limited case series have been reported to recur frequently in kidney transplants and have a negative impact on allograft survival.

Study Design

Retrospective database review.

Setting & Participants

189,211 primary kidney transplants in the United Network for Organ Sharing (UNOS) database from September 1987 to May 2007.

Predictor or Factor

MPGN-I (811 patients; 0.4%), MPGN-II (179 patients; 0.1%), other GN (58,129 patients; 30.7%), and all other diagnoses (130,092 patients; 68.7%).

Outcomes

Death-censored and non–death-censored allograft survival.

Results

Compared with controls, patients with MPGN-I and MPGN-II were significantly younger at the time of transplant, with a median age of 36 and 27 years compared with 44 years in the GN group and 46 years in all other disease groups, respectively (all P < 0.001). Mortality in patients with MPGN-I (8.8%) was significantly lower compared with the GN (11.3%; P = 0.02) and other disease (16.6%; P < 0.001) populations and lower in those with MPGN-II (9.5%) compared with the other disease (16.6%; P = 0.01) population. Graft failure rates were significantly higher in the MPGN-I (44.5%) cohort, but not in the MPGN-II (45.3%) cohort compared with the GN (38.0%) population (P < 0.001 and P = 0.05, respectively); neither MPGN cohort differed from the other disease (43.0%) population (P = 0.4 and P = 0.5). Overall, 10-year death-censored graft survival was similar for MPGN-I (56.2%) and MPGN-II (57.5%); both were significantly worse than for GN (65.2%; P < 0.001 and P = 0.003, respectively), and only MPGN-I was significantly worse than the other disease (60.0%) population (P = 0.004). Of allograft failures with a reported cause, disease recurrence was the primary cause in 36 (14.5%) MPGN-I and 18 (29.5%) MPGN-II transplant recipients and was significantly higher compared with 879 (6.6%) GN and 1,319 (4.4%) all-other-disease recurrence failures (P < 0.001).

Limitations

Limited pretransplant clinical and biopsy data.

Conclusions

A diagnosis of MPGN-I or MPGN-II has a significant negative impact on overall primary allograft survival compared with other forms of glomerulonephritis, whereas only MPGN-I has a significant, but modest, negative effect compared with other causes of end-stage renal disease.

Section snippets

Methods

Data were requested and received for the UNOS Standard Transplant Analysis and Research Files for September 1987 to May 2007. Specifics relating to the nature of the UNOS database and data collection methods are described in detail elsewhere.²⁰ Analysis was limited to single-organ kidney transplants that took place between September 1987 and December 2005. Combined kidney-liver, kidney-pancreas, and other multiorgan transplants were excluded from the analysis regardless of cause of ESRD. Data

Results

For the period of the study, 1987-2005, there were 189,211 primary single-organ kidney transplants performed in the United States contained in the UNOS database. Of these, 811 (0.4%) were in patients with a reported ESRD diagnosis of MPGN-I and 179 were in patients with MPGN-II (0.1%). The remaining 188,221 (99.5%) primary kidney transplants were grouped as 58,129 GN (30.7%) and 130,092 all other diseases (68.7%). Complete follow-up data, death, 10-year graft survival, or graft failure were

Discussion

There can be little doubt that MPGN is a rare disease. During the 20-year period of the present study, patients with MPGN-I and MPGN-II together constituted only 0.5% of transplant recipients. This is consistent with the most recent USRDS data that reported incidences of MPGN-I of 0.3% and MPGN-II of 0.03% in the US ESRD population.²¹ Although MPGN typically is thought of as more common in the pediatric population, UNOS data suggest otherwise because median ages at transplant for MPGN-I and

Acknowledgements

We acknowledge the contributions of Dr Donald Stablein and Karen Martz in analyzing the NAPRTCS database.

Support: This work was supported in part by Health Resources and Services Administration contract 234-2005-370011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Financial

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Complement 3 glomerulopathy (C3G) is a rare inflammatory kidney disease mediated by dysregulation of the alternative complement pathway. No targeted therapy exists for this aggressive glomerulonephritis. Efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) (measured by complement biomarkers) of iptacopan were assessed in patients with C3G.
In this phase 2, multicenter, open-label, single-arm, nonrandomized study, adults with biopsy-proven, native kidney C3G (native cohort) and kidney transplant recipients with C3G recurrence (recurrent kidney transplant [KT] cohort) received iptacopan twice daily (bid) for 84 days (days 1–21: 10–100 mg; days 22–84: 200 mg). The primary end point was the urine protein-to-creatinine ratio (UPCR; native cohort) and the change in the C3 deposit score of kidney biopsy (recurrent KT cohort). The complement pathway measures included Wieslab assay, soluble C5b9, and serum C3 levels.
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Citation Excerpt :
Other than an association with monoclonal gammopathy23,24 (and hence higher malignancy-related mortality risk), it is not clear whether the poorer survival identified is a true effect (as compared to sample size) and, if so, what reasons may contribute to the same. Conversely, a recent review from the United Network for Organ Sharing database reported lower mortality rates for patients with MPGN types I and II compared with other forms of GN.18 It is important to emphasize that these cohorts reflect not just those reaching ESRD and needing dialysis but also those deemed fit to undergo renal transplantation.
Glomerulonephritis (GN) is the primary diagnosis in 20% to 40% of patients receiving a renal transplant. Here we studied patient survival and graft outcomes in patients with GN transplanted in the UK. UK Renal Registry data were used to analyze patient survival and graft failure in incident transplant patients between 1997 to 2009 who had a diagnosis of primary GN, in comparison to patients transplanted with adult polycystic kidney disease (APKD) or diabetes. Multivariable regression analysis adjusted for age, sex, donor type, ethnicity, donor age, time on dialysis, human leukocyte antigen mismatch, cold ischemic time, and graft failure (for patient survival). Patients were followed up through December 2012. Of 4750 patients analyzed, 2975 had GN and 1775 APKD. Graft failure was significantly higher in membranoproliferative glomerulonephritis (MPGN) type II (hazard ratio: 3.5, confidence interval: 1.9–6.6), focal segmental glomerulosclerosis (2.4, 1.8–3.2), MPGN type I (2.3, 1.6–3.3), membranous nephropathy (2.0, 1.4–2.9), and IgA nephropathy (1.6, 1.3–2.0) compared to APKD. Survival was significantly reduced in patients with MPGN type II (4.7, 2.0–10.8), and those with lupus nephritis (1.8, 1.1–2.9). Overall graft failure for patients with GN was similar to those with diabetes. Thus, in comparison to outcomes in APKD, graft survival is significantly lower in most GNs, with variation in outcomes between different GNs. This information should assist in pretransplant counseling of patients. Further study is required to understand the reduced survival seen in lupus nephritis and MPGN type II, and to improve overall graft outcomes.
Advances in the understanding of complement mediated glomerular disease: Implications for recurrence in the transplant setting
2015, American Journal of Transplantation
Recent advances in the understanding of the role of complement in glomerular disease allow for more accurate assessment of the risk of disease recurrence after transplantation, and inform the development of targeted treatment strategies to overcome specific defects in the alternate pathway of the complement system. These advances along with remaining knowledge deficits are reviewed with specific relevance to membranoproliferative glomerulonephritis (MPGN) and C3 glomerulopathy, a heterogenous group of diseases with a high rate of recurrence leading to allograft failure. Recommendations to establish an accurate diagnosis and inform therapeutic decision making in transplant candidates with a histologic diagnosis of MPGN are provided.
Modeling C3 glomerulopathies: C3 convertase regulation on an extracellular matrix surface
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: Originally published online January 7, 2011.

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Original InvestigationTransplantationAllograft Failure in Kidney Transplant Recipients With Membranoproliferative Glomerulonephritis

Background

Study Design

Setting & Participants

Predictor or Factor

Outcomes

Results

Limitations

Conclusions

Section snippets

Methods

Results

Discussion

Acknowledgements

Lancet

Am J Med

Am J Med

Kidney Int

Am J Kidney Dis

Am J Kidney Dis

Kidney Int

Kidney Int

Idiopathic membranoproliferative glomerulonephritis in childhood

Pediatr Nephrol

New approaches to the treatment of dense deposit disease

J Am Soc Nephrol

Membranoproliferative glomerulonephritis with disruption of the glomerular basement membrane

Clin Nephrol

Recurrence of an original glomerular lesion in three renal allografts

Transplant Proc

Renal transplantation in mesangioproliferative glomerulonephritis (MPGN): relationship between the high frequency of recurrent glomerulonephritis and hypocomplementemia

Kidney Int Suppl

Recurrent glomerulonephritis after renal transplantation

Annu Rev Med

Original Investigation
Transplantation
Allograft Failure in Kidney Transplant Recipients With Membranoproliferative Glomerulonephritis