Novel Treatments Paradigms: Membranous Nephropathy

Primary membranous nephropathy (MN) is a kidney-specific autoimmune glomerular disease and the leading cause of nephrotic syndrome (NS) in White adults, usually caused by antiphospholipase A2 receptor (PLA2R) antibodies, although several new target antigens have been recently identified. It is characterized by the diffuse thickening of the glomerular basement membrane secondary to immune complex deposition. In patients with persistent NS without response to maximizing conservative therapy including the use of renin-angiotensin system (RAS) blockers, the use of immunosuppressive agents is warranted. However, the optimal immunosuppressive treatment has not yet been established. Classical immunosuppressants, such as cyclophosphamide plus steroids, are effective but may cause clinically relevant adverse effects, limiting their use. Rituximab offers efficacy with a better safety profile whereas calcineurin inhibitors (CNIs) are marred by high relapse rates and nephrotoxicity. Nevertheless, up to 30% of patients fail to respond to standard therapy. Novel and specific therapies targeting B cells and plasma cells have shown encouraging preliminary results, in terms of clinical efficacy and safety profile, especially in patients with poor tolerance or refractory to conventional treatments. In this brief review, we discuss the benefits and limitations of the current therapeutic approach to MN and describe emerging novel therapies that target its pathogenesis.