Clinical features and outcomes of immune complex-membranoproliferative glomerulonephritis and C3 glomerulopathy: a multicenter observational cohort study analyzing kidney biopsy cases.

Background: Membranoproliferative glomerulonephritis (MPGN) has two subtypes based on immunofluorescence findings: complement 3 glomerulopathy (C3G) and immune complex-mediated MPGN (IC-MPGN). This study investigated the characteristics and prognosis of patients with MPGN.

Methods: This retrospective study analyzed data from 18 hospitals between 1979 and 2018. Among 21,697 patients, 620 were diagnosed with MPGN, 570 with IC-MPGN, and 50 with C3G.

Results: The C3G group had a lower estimated glomerular filtration rate (eGFR; 49.9 ± 40.7 mL/min/1.73 m2 vs. 62.7 ± 36.5 mL/min/1.73 m2, p = 0.02) compared with the IC-MPGN group. This trend continued at 6 months: patients with reduced renal function were 36.7% in the C3G group (p = 0.11). However, the IC-MPGN group had significantly higher levels of proteinuria (4.7 ± 4.2 g/g vs. 2.9 ± 2.6 g/g, p < 0.001). The 50.7% of patients with IC-MPGN had nephrotic-range proteinuria. Serum C3 levels were significantly lower in the C3G group (p = 0.04). Hepatitis B surface antigen positivity was significantly more frequent in the IC-MPGN group (35.3% vs. 7.0%, p < 0.001). Interstitial fibrosis and tubular atrophy, markers of chronic kidney damage, were more prevalent in the IC-MPGN group (p ≤ 0.001). During a follow-up period of 122.4 ± 124.2 months, a total of 159 patients (27.7%) with MPGN progressed to end-stage kidney disease (ESKD): 151 IC-MPGN (28.4%) and eight C3G patients (19.0%) (p = 0.28). The adjusted risk of 40% eGFR decline, ESKD, and mortality was not different between groups.

Conclusion: The C3G group initially showed severe renal dysfunction. Despite having fewer chronic histological findings, the long-term renal outcomes for C3G remained as unfavorable as those for IC-MPGN. This suggests that C3G may require careful monitoring and treatment.