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28 August 2013

The podocin mutation R229Q and early recurrence (within the first year) of glomerular disease after renal transplantation

Hesham MoheyBCDEF, Lise ThibaudinABCD, Blandine LaurentBCD, Francois BerthouxABCDEFG

DOI: 10.12659/AOT.884003

Ann Transplant 2013; 18:436-442


BACKGROUND: Podocin is a key protein involved in the pathogenesis of steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis (FSGS) and is characterized by a high rate of early recurrence after renal transplantation (RTx) in children and adults.

MATERIAL AND METHODS: We studied 206 RTx adult recipients: 187 with a diagnosis of glomerular nephropathy, GN (biopsy-proven in 149, clinical in 38), plus 19 with unknown diagnosis as original kidney disease (OKD), the NPHS2 gene polymorphism, G755A, and correlated with the presence of early recurrence of OKD within the first year (proteinuria over 1 g/day and graft-biopsy proven).

RESULTS: The A allele podocin gene mutation frequency was 3.4% (14/412) overall – 7.1% (4/56) in FSGS as expected, but surprisingly 5.7% (6/106) in IgA nephropathy. Fifty recipients (24.3%) developed proteinuria >1 g/d, with 12 recipients demonstrating early clinico-pathological recurrence by 1 year (5.8%) with 5/28 in FSGS, 2/53 in IgAN, 2/14 in membranoproliferative GN (with 1 graft loss within the first year), 1/19 in crescentic GN, 1/19 in unknown disease, and 1/38 in clinical GN. Only 2 recurrent patients (both with FSGS) had the R229Q podocin mutation (16.7%).

CONCLUSIONS: The podocin mutation R229Q may play a role in the pathogenesis of FSGS and in early recurrence after transplantation, but does not allow accurate prediction of recurrence or the associated potential for prevention.

Keywords: Glomerulonephritis, Recurrence, podocin gene, IgA nephropathy, focal segmental glomerulosclerosis, renal transplantation

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Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358