Changing treatment paradigms for membranous nephropathies

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome (NS) in non-diabetic adult population.The immunopathogenesis of MN is mostly related to the presence of anti-phospholipase A2 receptor (PLA2R) antibodies (Ab), however, recent investigations have unveiled several new target antigens.The pathogenesis of MN primarily involves the formation and deposition of immune complexes, consisting of immunoglobulins and complement, leading to podocyte injury and disruption of the glomerular basement membrane (GBM) leading to proteinuria, often progressing to NS and, if persistent, to kidney failure.The latest KDIGO 2021 recommends that patients with a moderate to high risk of progression be treated with immunosuppressive (IS) therapy.(1) Options include calcineurin inhibitor (CNI), a combination of cyclophosphamide (CYC) and corticosteroids, and rituximab (RTX).However, the use of CNI is declining due to the increased risk of relapse and the combination of CYC and corticosteroids (cyclical therapy) is associated with increased risk of infection, osteoporosis, diabetes mellitus, weight gain, hemorrhagic cystitis and infertility.(3) In recent years, there has been significant interest in the use of RTX in the management of MN.Randomised clinical trials (RCT) like GEMRITUX and MENTOR have shown a favourable safety profile for RTX, positioning it as the preferred treatment for MN in the current era.(4,5) In the RI-CYCLO trial, the complete remission rate (CR) was lower in the RTX group compared to the modified ponticelli regimen (mPR) group (16% versus 32%) at 12 months.Despite the substantial response rates to RTX and mPR, 20-30% of cases have