Nephrotic syndrome and rituximab: facts and perspectives

Idiopathic nephrotic syndrome is the most frequent glomerular disease that presents during childhood and is mainly due to minimal change nephropathy (MCNS) and focal-segmental glomerulosclerosis (FSGS). Its treatment is still challenging, with up to 50% of the patients who are initially steroid sensitive (usually MCNS) being frequent relapsers and requiring additional long-term immunosuppression. However, current immunosuppressive regimens are associated with severe toxicity. Only half of the steroid-resistant patients (usually FSGS) achieve long-term remission even with intensive immunosuppression and plasma exchange. Rituximab (RTX), a chimeric monoclonal antibody inhibiting CD20-mediated B-cell proliferation and differentiation, has recently gained attention as a potentially successful therapy for complicated idiopathic nephrotic syndrome in children. A number of case reports and one prospective non-controlled multicenter trial point to the beneficial effects of RTX as a rescue therapy in children with steroid/cyclosporine-dependent or -resistant nephrotic syndrome. However, publication bias often results in positive outcomes being more likely to be reported than negative ones and, in particular, the safety profile of this drug in this group of patients remains unclear. Therefore, controlled randomized studies are required to assess this issue, to develop treatment guidelines, to evaluate the therapeutic and economical efficacy, and to define criteria for the selection of patients.