Therapy and outcomes of C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis.

Abstract

Data on therapy and outcome of dense deposit disease (DDD), C3 glomerulonephritis (C3GN), and immune-complex MPGN (IC-MPGN) in children are limited. In this retrospective single-center study from 2007 to 2019, kidney biopsies were reviewed to include patients aged <18-yearswith C3 glomerulopathy and IC-MPGN. Initial immunosuppression comprised prednisolone, mycophenolate mofetil (n= 51), tacrolimus (n= 11), and/or IV cyclophosphamide (n= 20). Clinicopathological features, response to therapy, and adverse outcome (eGFRcr< 15mL/min/1.73m2 or death) were evaluated. A total of 92 patients were classified as DDD (n= 48, 52.2%), C3GN (n= 26, 28.3%), and IC-MPGN (n= 18, 19.6%) by immunohistochemistry and electron microscopy; 8 patients with DDD were misclassified as IC-MPGN on immunofluorescence. At last follow-up (median 4.3years), complete or partial remission occurred in 28.5, 36.1, and 16.7% patients with DDD, C3GN, and IC-MPGN, respectively. Serum albumin at onset < 2.5g/dL (HR = 0.29, P= 0.005) and persistently low serum C3 (HR = 0.34, P= 0.02) were associated with lack of remission. The 5-year kidney survival was 62.6, 85.5, and 88.5% in patients with DDD, C3GN, and IC-MPGN, respectively (log-rank, P= 0.006). Presentation as rapidly progressive GN (HR = 11.2, P< 0.001), age > 10yearsat onset (HR = 4.0, P= 0.004), and DDD (HR = 4.2, P= 0.02) were independently associated with adverse outcome; achieving remission was protective (HR = 0.04; P< 0.001). Outcome in patients with C3 glomerulopathy and IC-MPGN wasunsatisfactory, and only a small proportion of patients achieved complete or partial remission. Patients with DDD were more likely to present with rapidly progressive GN and were at higher risk of adverse outcomes, including kidney failure.