Outcome of Patients Transplanted for C3 Glomerulopathy and Primary Immune Complex-Mediated Membranoproliferative Glomerulonephritis

Abstract

Introduction: Approximately 50% of patients with C3 glomerulopathy (C3G) and primary immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) reach kidney failure 10 years after diagnosis. Because these patients are generally young, the majority will be listed for kidney transplantation (KTx). However, reported outcomes in patients transplanted for C3G and IC-MPGN are heterogeneous and conflicting, because they are mainly based on retrospective monocentric studies. We thus aimed to provide detailed multicenter data on these patients, taking advantage of the ongoing nationwide Swiss Transplant Cohort Study (STCS).

Methods: We analyzed patient and graft outcomes, including the risk of graft loss in relation to recurrence of glomerulopathy.

Results: Forty-one (10 C3G and 31 IC-MPGN) transplanted recipients were included with a mean age at transplantation of 48 ± 16 years. Living donors provided 53% of the organs. During a mean follow-up of 4.7 years, 7 patients (4 C3G and 3 IC-MPGN) presented disease recurrence with a mean time to recurrence of 1.2 years. New-onset or rapidly increasing proteinuria was an early marker of recurrence, preceding significant decline in estimated glomerular filtration rate (eGFR). Following recurrence, 28% lost their graft, compared to 11% of patients without recurrence. Disease recurrence was the primary cause of graft loss in all patients. Finally, 14% of patients died during follow-up.

Conclusion: This study provides important insights into the epidemiology and outcome of patients with C3G and IC-MPGN and their grafts after KTx. The data also suggest that proteinuria may serve as an early biomarker of disease recurrence and should be considered in patient management as well as an endpoint in current clinical trials using novel complement modulators.

Keywords: C3 glomerulopathy; cohort study; complement pathway; graft outcome; kidney transplantation; membranoproliferative glomerulonephritis.

Graphical abstract

Figure 1

Cumulative incidence of graft loss over time, comparing 41 patients transplanted for C3 glomerulopathy and primary immune complex-mediated membranoproliferative glomerulonephritis and 2590 kidney transplant recipients transplanted for other causes. Full red line: cumulative incidence of graft loss for patients transplanted for C3 glomerulopathy and primary immune complex-mediated membranoproliferative glomerulonephritis (C3G/MPGN-KTx); dashed red lines: 95% confidence intervals. Full blue line: cumulative incidence of graft loss for patients transplanted for other causes (Other-KTx); dashed blue lines: 95% confidence intervals. CI, cumulative incidence; KTx, Kidney transplantation.

Figure 2

Cumulative incidence of graft dysfunction over time, comparing 41 patients transplanted for C3 glomerulopathy and primary immune complex-mediated membranoproliferative glomerulonephritis and 2590 kidney transplant recipients transplanted for other causes. (a) Comparison between the whole cohort and patients transplanted for C3 glomerulopathy and primary immune complex-mediated membranoproliferative glomerulonephritis. Full red line: cumulative incidence of graft dysfunction for patients transplanted for C3 glomerulopathy and primary immune complex-mediated membranoproliferative glomerulonephritis (C3G/MPGN-KTx); dashed red lines: 95% confidence intervals. Thick dashed blue line: cumulative incidence of graft dysfunction for patients transplanted for other causes (Other-KTx); thin dashed blue lines: 95% confidence intervals. (b) Comparison between patients transplanted for C3 glomerulopathy (n = 10) and patients transplanted for primary immune complex-mediated membranoproliferative glomerulonephritis (n = 31). Full red line: cumulative incidence of graft dysfunction for patients transplanted for C3 glomerulopathy (C3G-KTx); dashed red lines: 95% confidence intervals. Full blue line: cumulative incidence of graft dysfunction for patients transplanted for primary immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN-KTx); dashed blue lines: 95% confidence intervals. CI, cumulative incidence; KTx, kidney transplantation.

Figure 3

(a) Cumulative incidence of recurrence of disease over time, among 10 patients transplanted for C3 glomerulopathy and 31 patients transplanted for primary immune complex-mediated membranoproliferative glomerulonephritis. (b) Full red line: cumulative incidence of recurrence for patients transplanted for C3 glomerulopathy (C3G-KTx); dashed red lines: 95% confidence intervals. Full blue line: cumulative incidence of recurrence for patients transplanted for primary immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN-KTx); dashed blue lines: 95% confidence intervals. KTx, kidney transplantation.

Figure 4

Evolution of (a) kidney function and (b) proteinuria during follow-up, comparing recurrent and nonrecurrent C3G/IC-MPGN kidney transplant recipients. Red squares and line: recurrent group; black dots and line: non-recurrent group. C3G, C3 glomerulopathy; IC-MPGN, immune complex-mediated membranoproliferative glomerulonephritis.

Figure 5

Cumulative incidence of graft dysfunction among 41 patients with recurrent and non-recurrent C3G/IC-MPGN after kidney transplantation. Full red line: cumulative incidence of graft dysfunction for the recurrent group; dashed red lines: 95% confidence intervals. Full blue line: cumulative incidence of graft dysfunction for the non-recurrent group; dashed blue lines: 95% confidence intervals. C3G, C3 glomerulopathy; CI, cumulative incidence; IC-MPGN, immune complex-mediated membranoproliferative glomerulonephritis.

Figure 6

Cumulative incidence of death during follow-up, between 31 patients transplanted for primary immune complex-mediated membranoproliferative glomerulonephritis and 2590 kidney transplant recipients transplanted for other causes. Full red line: cumulative incidence of death for patients transplanted for primary immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN-KTx); dashed red lines: 95% confidence intervals. Thick dashed blue line: cumulative incidence of death for patients transplanted for other causes (Other-KTx); thin dashed blue lines: 95% confidence intervals. C3G, C3 glomerulopathy; CI, cumulative incidence; IC-MPGN, immune complex-mediated membranoproliferative glomerulonephritis; KTx, kidney transplantation.