Demographic, clinical characteristics and treatment outcomes of immune-complex membranoproliferative glomerulonephritis and C3 glomerulonephritis in Japan: A retrospective analysis of data from the Japan Renal Biopsy Registry

Abstract

The reclassification of membranoproliferative glomerulonephritis (MPGN) into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G) based on immunofluorescence findings in kidney biopsies has provided insights into these two distinct diseases. C3G is further classified into dense deposit disease and C3 glomerulonephritis (C3GN) based on electron micrographic findings. Although these diseases have poor outcomes, limited Japanese literature confined to small, single-center cohorts exist on these diseases. We retrospectively analyzed 81 patients with MPGN type I and III from 15 hospitals in the Japan Renal Biopsy Registry to compare demographic, clinical characteristics and treatment outcomes of patients with IC-MPGN to those with C3GN. Of the 81 patients reviewed by immunofluorescence findings in kidney biopsies, 67 patients had IC-MPGN and 14 patients had C3GN. Age at diagnosis and systolic and diastolic pressure were higher and proteinuria and impaired renal function were significantly more prevalent in patients with IC-MPGN than those with C3GN. About 80% of the patients in both groups were treated with immunosuppressive therapy. At last follow-up (median 4.8 years), complete remission rate of proteinuria was significantly higher in patients with C3GN (64.3%) than in those with IC-MPGN (29.9%; P = 0.015). The renal survival rate was lower in patients with IC-MPGN when compared to C3GN (73.1% vs. 100%; log-rank, P = 0.031). Systolic blood pressure and renal function at baseline were independent predictors of progression to end-stage kidney disease. The overall prognosis of patients with C3GN is more favorable than for patients with IC-MPGN.

C3 glomerulopathy: Understanding an ultra‐rare complement‐mediated renal disease

“…While the natural history of C3G is not well defined, hematuria, proteinuria, and nephrotic syndrome are the most common signs and symptoms (Caravaca-Fontán et al, 2021;Michels et al, 2022;Nakagawa et al, 2021;Pınarbas ¸ı et al, 2021). About 75% of pediatric C3G patients present with low C3 as compared to 50% of adults.…”

“…C3G is also associated with the development of drusen, making an ophthalmologic evaluation an essential part of an C3G patient's regular care (Nasr et al, 2009). While the natural history of C3G is not well defined, hematuria, proteinuria, and nephrotic syndrome are the most common signs and symptoms (Caravaca‐Fontán et al, 2021; Michels et al, 2022; Nakagawa et al, 2021; Pınarbaşı et al, 2021). About ~75% of pediatric C3G patients present with low C3 as compared to ~50% of adults.…”

New-onset and relapse of nephrotic syndrome following COVID-19 vaccination: a questionnaire survey in Japan

“…These cytokines may play a role in exacerbating quiescent or subclinical glomerular diseases via a mechanism similar to that proposed for viral infections, which is a known trigger for de novo and relapsing glomerular diseases [ 24 ]. Actually, our survey showed new-onset and relapse of NS following COVID-19 vaccination in patients with not only MCD, but also various glomerular diseases, including focal segmental glomerulosclerosis, IgAN, membranous nephropathy, membranoproliferative glomerulonephritis, and C3 glomerulopathy, which is a rare kidney disorder [ 25 ]. Notably, in this study, one patient was newly diagnosed with membranous nephropathy following a kidney biopsy that was performed because of new-onset NS following COVID-19 vaccination, thus suggesting that such immune activation may be largely related to the mechanism of onset of glomerular diseases.…”

Diagnostic Problems in C3 Glomerulopathy

“…However, these updated classification criteria do not clarify how to differentiate the two diseases, which are clinically the best in terms of diagnosis, optimal treatment, and prognosis. In turn, the recent criteria for differentiating C3G from IC-MPGN are based on the predominance of C3 rather than immunoglobulins, which are assessed using fluorescence microscopy [ 11 ].…”