Obinutuzumab Treatment in Rituximab- and Bortezomib-Resistant Phospholipase A2 Receptor Antibody-Positive Membranous...

Primary membranous nephropathy (MN) is a frequent cause of nephrotic syndrome in adults and is commonly linked to circulating autoantibodies against the M-type phospholipase A2 receptor (PLA2R). Rituximab has proven effective as a B-cell-depleting therapy in many patients; however, a significant proportion eventually develop resistance. We report the case of a 54-year-old man with PLA2R antibody-positive primary MN who did not respond to multiple immunosuppressive therapies, including cyclophosphamide, calcineurin inhibitors, repeated rituximab courses, and bortezomib. Despite ongoing nephrotic syndrome and declining renal function, treatment with obinutuzumab resulted in rapid and sustained clinical improvement. This was associated with a substantial reduction in proteinuria, normalization of serum albumin, and recovery of renal function. Our findings suggest that obinutuzumab may offer an effective therapeutic option for highly refractory PLA2R antibody-positive MN and that achieving more complete B-cell depletion could overcome resistance to conventional anti-CD20 therapy.