B Cell-Targeted Therapy in Membranous Nephropathy: Time for a Randomized Trial

Membranous nephropathy is a common immune-mediated glomerular disease and remains the leading cause of nephrotic syndrome in Caucasian adults.1 Although the disease progresses relatively slowly in most patients, approximately 40% eventually develop end-stage renal disease (ESRD).2 Despite this risk, there has been little progress in the treatment of this condition over the last 30 years. While available immunosuppressive therapies, including corticosteroids, alkylating agents, and calcineurin inhibitors, are at least partially successful in reducing proteinuria in membranous nephropathy, their use is controversial, and they all are associated with signifi cant adverse effects and a high relapse rate.3 This set of circumstances holds particularly true in the case of cyclophosphamide, where side effects include risk of infertility and the long-term increased chance of malignancy. Since membranous nephropathy is a disease with remissions and relapses, repeated use of cyclophosphamide results in a progressive increase in long-term risks. There is a need to evaluate new treatments for patients with membranous nephropathy that result in a higher response rate, lower relapse rate, and fewer adverse effects.