Rituximab in idiopathic membranous nephropathy: A one-year prospective study

Currently available monoclonal antibodies against the B cell surface antigen CD20 have been employed to explore whether specific inhibition of B cells may help improve the outcome of idiopathic membranous nephropathy (IMN) and may avoid the side effects of steroids and immunosuppressants. This prospective, observational study evaluated the 1-yr outcome of eight IMN patients with persistent (>6 mo) urinary protein excretion > 3.5 g/24 h given four weekly infusions of the anti-CD20 antibody rituximab (375 mg/m²) At 3 and 12 mo, proteinuria significantly decreased from mean (± SD) 8.6 ± 4.2 to 4.3 ± 3.3 (-51%, P <0.005) and 3.0 ± 2.5 (-66%, P <0.005) g/24 h, albumin fractional clearance from 2.3 ± 2.1 to 1.2 ± 1.7 (-47%, P <0.05) and 0.5 ± 0.6 (-76%, P <0.003), and serum albumin concentration increased from 2.7 ± 0.5 to 3.1 ± 0.3 (+21%, P <0.05) and 3.5 ± 0.4 (+41%, P <0.05) mg/dl. At 12 mo, proteinuria decreased to ≤0.5 g/24 h or ≤3.5 g/24 h in two and three patients, respectively. Proteinuria decreased in the remaining patients by 74%, 44%, and 41%, respectively. Body weight, diastolic BP, and serum cholesterol progressively decreased in parallel with an improvement of edema in all patients. Renal function stabilized (Δl/creatinine: +0.002 ± 0.007). CD20 B lymphocytes fell below normal ranges up to study-end. No patient had major drug-related events or major changes in other laboratory parameters. Rituximab thus promotes sustained disease remission in patients otherwise predicted to progress to ESRD, and it is safe. The long-term risk/benefit profile of this novel, disease-specific approach seems much more favorable to that of commonly employed immunosuppressive drugs.