Novel treatment options in rituximab-resistant membranous nephropathy patients

The conventional treatment options (including alkylating agents, steroids, calcinurine inhibitors) have been largely replaced by anti-CD20 antibodies to achieve remission of nephrotic proteinuria in primary membranous nephropathy (PMN) patients. Two-third of rituximab-receiving PMN patients develop remission of proteinuria, and the results of MENTOR trial turned this drug into the first-line therapeutic agent in non-severe cases. However, in 20-40% of patients, remission is not achieved. Therefore, rituximab-resistant membranous nephropathy cases are increasingly reported. Different molecular mechanisms have been implicated in this context resulting in the introduction of new biologic agents. Second-generation anti-CD20 antibodies and other options such as plasma cell depleting agents and proteasome inhibition might lead to a novel treatment paradigm for patients with PMN.