Newer B-cell and plasma-cell targeted treatments for rituximab-resistant patients with membranous nephropathy

Abstract

Membranous nephropathy is the most common cause of nephrotic syndrome in adults. While spontaneous remission occurs in approximately one-third of cases, another one-third of patients receiving immunosuppressive therapy demonstrate treatment resistance. This resistance, coupled with persistent proteinuria, significantly increases the risk of kidney failure. Alternative therapies, including B-cell and plasma-cell targeted treatments have been explored in isolated cases and case series. In this review, we examine the available evidence on the treatment of resistant and relapsing membranous nephropathy with a particular focus on B- and plasma-cell directed therapies.

Keywords: glomerulonephritis; membranous nephropathy; plasma-cell targeted; rituximab; treatment.

Figure 1:

Overview of available treatments for resistant and relapsing MN and their mechanisms of action. B-cell targeted therapies, including obinutuzumab and ofatumumab, function as anti-CD20 monoclonal antibodies that deplete B cells, thereby reducing autoantibody production. Plasma-cell-directed therapies, such as bortezomib—a proteasome inhibitor—and felzartamab and daratumumab, which target CD38-expressing plasma cells, all contribute to lowering pathogenic autoantibody levels. (Created with BioRender.com.)