Recurrent Nephrotic Syndrome in Homozygous Truncating NPHS2 Mutation Is Not Due to Anti-Podocin Antibodies

Abstract

Mutations in NPHS2 are a common cause of focal segmental glomerulosclerosis (FSGS). It was initially assumed that FSGS caused by a genetically defective protein in the native kidney would not recur after transplantation; however, description of three patients with NPHS2 missense mutations challenged the validity of this assumption. A possible mechanism of recurrence in cases with stop-codon mutations is the formation of auto-antibodies against the truncated protein. In this case report, we describe a 9-year-old girl with the R138X NPHS2 mutation who presented with recurrent nephrotic syndrome 4 years after renal transplantation from a deceased donor, and was treated with plasmapheresis with a partial response. Renal histology did not demonstrate glomerular immunoglobulin deposition and an extensive search for anti-podocin antibodies based on indirect Western blot with recombinant podocin, was negative, as was the test for glomerular permeability factor (Palb). Taken together these findings confirm the possibility of post transplantation nephrotic syndrome in patients with NPHS2 mutations. Lack of immunoglobulin deposition, absence of circulating anti-podocin antibodies, and normal Palb suggest that other, unknown pathogenetic mechanisms are implicated.