Physiopathologie, démarche diagnostique et avancées thérapeutiques dans les glomérulonéphrites extra-membraneuses

Abstract

Membranous nephropathy (MN) accounts for about 20% of cases of nephrotic syndrome in the adult. Thickening of glomerular capillary walls results from subepithelial formation of immune deposits containing IgG and the membrane attack complex of complement, which is the major mediator of proteinuria, and antigens. Idiopathic forms of MN (IMN) represent 70 to 80% of all cases. A major breakthrough was the identification of the podocyte antigen PLA2R as the target of circulating antibodies in about 70% of IMN, which confirmed that the disease was auto-immune in nature. The optimal treatment of patients with IMN is still a matter of debate. Thirty to 40% of affected patients will undergo spontaneous remission, usually within one year from disease onset, whereas about one third will progress to end-stage kidney disease. Both the evidence that B cells play a key role in the pathogenesis of IMN and drug toxicity led to target B-cells with rituximab. Rituximab induced remission of nephrotic syndrome in 60 to 80% of the patients with long-lasting proteinuria despite blockade of the renin-angiotensin system and in patients who had previously failed other treatments. Because of the lack of randomized controlled trial (RCT) using rituximab and of high rate of spontaneous remission, a French non-blinded, parallel group RCT was performed to compare rituximab added to supportive therapy, to supportive therapy alone, in patients with persistent nephrotic syndrome.