A child with semaphorin 3b-associated membranous nephropathy effectively treated with obinutuzumab after rituximab resistance

We report the case of a child presenting at 2  years of age with steroid-resistant nephrotic syndrome diagnosed upon kidney biopsy as semaphorin 3B (SEMA3B)-associated primary membranous nephropathy. The patient responded to treatment with cyclosporine, but invariably relapsed upon tapering of this agent. Therefore, at age 9, he was successful ly treated with rituximab to overcome cyclosporine dependence. However, after the second rituximab infusion, a rapid reconstitution of CD19 + B cells and a relapse of proteinuria occurred, requiring reintroduction of cyclosporine. Obinutuzumab, a type II anti-CD20 monoclonal antibody, was then i nfused inducing prolonged CD19 + B cell depletion and remission of proteinuria despite discontinuation of cyclosporine. A greater reduction in circulating anti-SEMA3B antibodies assessed by Western blot was observed after obinutuzumab compared with rituximab infusion.DiscussionObinutuzumab was safe and well-tolerated, and may therefore represent an effective therapeutic alternative in children with primary MN and rituximab resistance.
Source: Pediatric Nephrology - Category: Urology & Nephrology Source Type: research