Rituximab for Treatment of Membranoproliferative Glomerulonephritis and C3 Glomerulopathies

Abstract

Membranoproliferative glomerulonephritis (MPGN) is a histological pattern of injury resulting from predominantly subendothelial and mesangial deposition of immunoglobulins or complement factors with subsequent inflammation and proliferation particularly of the glomerular basement membrane. Recent classification of MPGN is based on pathogenesis dividing MPGN into immunoglobulin-associated MPGN and complement-mediated C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Current guidelines suggest treatment with steroids, cytotoxic agents with or without plasmapheresis only for subjects with progressive disease, that is, nephrotic range proteinuria and decline of renal function. Rituximab, a chimeric B-cell depleting anti-CD20 antibody, has emerged in the last decade as a treatment option for patients with primary glomerular diseases such as minimal change disease, focal-segmental glomerulosclerosis, or idiopathic membranous nephropathy. However, data on the use of rituximab in MPGN, C3GN, and DDD are limited to case reports and retrospective case series. Patients with immunoglobulin-associated and idiopathic MPGN who were treated with rituximab showed partial and complete responses in the majorities of cases. However, rituximab was not effective in few cases of C3GN and DDD. Despite promising results in immunoglobulin-associated and idiopathic MPGN, current evidence on this treatment remains weak, and controlled and prospective data are urgently needed.

C3 Glomerulopathy

“…Only one patient with DDD and positive C3Nef treated solely with rituximab showed stable renal function and improvement of nephrotic syndrome after 30 months of follow-up, but C3Nef remained positive and C3 levels were always low [73]. In contrast, other cases with DDD and C3G initially treated with rituximab achieved partial or complete remission on eculizumab [72,74].…”

“…Other studies have suggested some benefit from the use of cyclophosphamide, mycophenolate mofetil and a combination of aspirin and dipyridamole. Current guidelines suggest treatment with steroids and cytotoxic agents, with or without plasmapheresis, only in patients with progressive disease with nephrotic range proteinuria and a decline of renal function [72]. Because C3G is a new diagnostic category, long-term data on renal transplants are lacking, but recurrence is probably as high as in idiopathic MPGN type I (up to 65% in some series).…”

“…Rituximab has emerged in the last decade as a treatment option for patients with various primary glomerular diseases. Despite data on the use of rituximab in MPGN and C3G being limited, patients with immunoglobulin-associated and idiopathic MPGN treated with rituximab showed a partial or complete response in the majority of cases [72]. It can be hypothesized that, in the presence of autoantibodies such as C3Nef, B-cell depleting therapy may have led to decreased production of C3Nef and, subsequently, stable renal function [72].…”

A Narrative Review on C3 Glomerulopathy: A Rare Renal Disease

“…Recurrence or de novo C3 GP may receive other therapies that are under trough evaluation as (i) compostatin that is a C3 inhibitory peptide; (ii) CP40 is a compostatin analog [70]; (iii) monoclonal antibodies against C3b [71], FB [72] and properdin [73]. Moreover, soluble complement receptor 1(CR1)) may prevent the dysregulated alternative pathway caused by abnormal production of C3 convertase.…”

“…Patients with nephrotic syndrome and a decline in renal function should receive oral CYC or MMF plus a low dose of daily or alternate-day corticosteroids [33]. If despite this treatment nephrotic syndrome persists or the renal function impairs, tacrolimus or RTX can be considered although the percentage of its beneficial effect is very low [35,70].…”