Treatment of idiopathic membranous nephropathy in adults: KDIGO 2012, cyclophosphamide and cyclosporine A are out, rituximab is the new normal

Abstract

The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines for glomerulonephritis shed light on the complex world of glomerulonephritis therapy. However, they may no longer apply to idiopathic membranous nephropathy, as recently concluded by the KDIGO 2019 Working Group. This is due to the discovery of autoantibodies such as anti-phospholipase A2 receptor (anti-PLA2R) that allow disease monitoring as well as to results from recent clinical trials, comparative cohort studies and meta-analyses. Perhaps the most disruptive of them is the Membranous Nephropathy Trial of Rituximab (MENTOR) trial comparing rituximab with cyclosporine A, which supports the superiority of rituximab in efficacy and safety. Furthermore, rituximab results compared favourably with the short-term results of classical clinical trials that supported the KDIGO 2012 recommendation of immunosuppressive cyclophosphamide-based regimens as first choice for active treatment of idiopathic membranous nephropathy. Thus, the KDIGO recommendations for cyclophosphamide-based regimens or calcineurin inhibitors as the first line of active treatment regimens for idiopathic membranous nephropathy with nephrotic syndrome may no longer apply. By contrast, rituximab-based regimens or other B-cell-targeted therapies appear to represent the present and future of membranous nephropathy therapy.