Anti-nephrin antibodies guide living donor kidney transplantation in a pediatric patient with primary focal segmental glomerular sclerosis

INTRODUCTION: Disease recurrence after kidney transplantation (KTx) remains a major challenge in patients with primary focal segmental glomerulosclerosis (pFSGS). Antibodies targeting the slit diaphragm protein nephrin have been identified in patients with early disease recurrence. Here, we describe monitoring and effective pre-transplant elimination of anti-nephrin antibodies in an adolescent with pFSGS prior to living-donor KTx. METHODS: Anti-nephrin antibodies were assessed in pre- and post-transplant serum samples by ELISA, Western blot and immunoprecipitation using three different nephrin proteins. RESULTS: Pre-transplant treatment including rituximab and repetitive therapeutic plasma exchanges resulted in effective and sustainable reduction of anti-nephrin antibodies. Allograft function has remained excellent without albuminuria over a follow-up of more than one year. Further analysis showed that the antibodies were cross-reactive with NEPH3 (filtrin), another key slit diaphragm protein. CONCLUSIONS: Monitoring and pre-transplant elimination of anti-slit diaphragm antibodies may become a standard, personalized approach in patients with pFSGS requiring KTx.