First Report of Recurrent Nephrotic Syndrome After Kidney Transplantation in a Patient With NUP93 Gene Mutations: A...

Mutations in nucleoporin 93 (NUP93) gene have been shown recently to be one of the very rare causes of genetic steroid-resistant nephrotic syndrome (SRNS). Until now, none of the 7 published cases with NUP93-SRNS, experienced recurrence of nephrotic syndrome (NS) after transplantation. Here, we present the first case of recurrent NS in a patient with NUP93-SRNS ever reported. A 3-year-old boy with infantile SRNS was started on chronic peritoneal dialysis because of end-stage renal failure owing to biopsy-proven focal segmental glomerulosclerosis (FSGS). At the age of 6 years, the boy received a renal allograft. The posttransplant period was uncomplicated until 1.7 years after transplantation, when the patient developed nephrotic proteinuria during a respiratory tract infection. Renal graft biopsy showed subtotal fusion of podocytes, which was compatible with an early histopathologic sign of recurrence of FSGS. Immediate treatment with daily plasma exchange (PE) was started at the second day. The proteinuria disappeared completely after the second PE. However, it reappeared after stopping daily PE. It disappeared again after reintroduction of daily PE, therefore PE-dependent recurrent NS was diagnosed and treatment with rituximab was given. After the first dose, proteinuria never reappeared despite stopping PE therapy. Surprisingly, next-generation sequencing revealed compound heterozygous mutations in exons 16 and 18 of the NUP93 gene (c.1772G>T - European founder allele and 1916T>C) and his parents confirmed heterozygous asymptomatic carriers. This is the first case of recurrent NS in a patient with NUP93 gene mutations, suggesting a new pathomechanism possibly involving the nucleoporins.