Kidney transplantation in children and adolescents with C3 glomerulopathy or immune complex membranoproliferative glomerulonephritis: a real-world study within the CERTAIN research network

Abstract

Background: Complement 3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are ultra-rare chronic kidney diseases with an overall poor prognosis, with approximately 40-50% of patients progressing to kidney failure within 10 years of diagnosis. C3G is characterized by a high rate of disease recurrence in the transplanted kidney. However, there is a lack of published data on clinical outcomes in the pediatric population following transplantation.

Methods: In this multicenter longitudinal cohort study of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, we compared the post-transplant outcomes of pediatric patients with C3G (n = 17) or IC-MPGN (n = 3) with a matched case-control group (n = 20).

Results: Eleven of 20 children (55%) with C3G or IC-MPGN experienced a recurrence within 5 years post-transplant. Patients with C3G or IC-MPGN had a 5-year graft survival of 61.4%, which was significantly (P = 0.029) lower than the 5-year graft survival of 90% in controls; five patients with C3G or IC-MPGN lost their graft due to recurrence during this observation period. Both the 1-year (20%) and the 5-year (42%) rates of biopsy-proven acute rejection episodes were comparable between patients and controls. Complement-targeted therapy with eculizumab, either as prophylaxis or treatment, did not appear to be effective.

Conclusions: These data in pediatric patients with C3G or IC-MPGN show a high risk of post-transplant disease recurrence (55%) and a significantly lower 5-year graft survival compared to matched controls with other primary kidney diseases. These data underscore the need for post-transplant patients for effective and specific therapies that target the underlying disease mechanism.

Keywords: Complement 3 glomerulopathy; Graft survival; Immune complex membranoproliferative glomerulonephritis; Pediatric kidney transplantation; Recurrence.

A higher resolution version of the Graphical abstract is available as Supplementary information

Fig. 1

A Overall recurrence-free kidney allograft survival over 60 months post-transplant in patients with C3 glomerulopathy (n = 17) or immune complex membranoproliferative glomerulonephritis (n = 3). The median time of survival without recurrence is marked by a vertical line. B Comparison of recurrence-free survival kidney allograft survival over 60 months post-transplant in the three subgroups of patients with C3 glomerulonephritis (C3GN, n = 12), dense deposit disease (DDD, n = 5), or immune complex membranoproliferative glomerulonephritis (IC-MPGN, n = 3)

Fig. 2

A Kidney allograft survival over 60 months post-transplant in patients with C3 glomerulopathy (n = 17) or immune complex membranoproliferative glomerulonephritis (n = 3) compared to matched controls (n = 20). There was a statistically significant difference (P = 0.029, log-rank test). B Comparison of kidney allograft survival over 60 months post-transplant in the three subgroups of patients with C3 glomerulonephritis (C3GN, n = 12), dense deposit disease (DDD, n = 5), or immune complex membranoproliferative glomerulonephritis (IC-MPGN, n = 3). There was no statistically significant difference (P = 0.52, log-rank test)

Fig. 3

Acute rejection-free survival over 60 months post-transplant in patients with C3 glomerulopathy (n = 17) or immune complex membranoproliferative glomerulonephritis (n = 3). There was no statistically significant difference (P = 0.79, log-rank test)