Recurrence of focal segmental glomerulosclerosis after renal transplantation in patients with mutations of podocin

Roberta Bertelli, Fabrizio Ginevri, Gianluca Caridi, Monica Dagnino, Silvio Sandrini, Marco Di Duca, Francesco Emma, Simone Sanna-Cherchi, Francesco Scolari, Tauro Maria Neri, Luisa Murer, Laura Massella, Giancarlo Basile, Gianfranco Rizzoni, Francesco Perfumo, Gian Marco Ghiggeri

Research output: Contribution to journalArticle

Abstract

Background: Posttransplant recurrence of focal segmental glomerulosclerosis (FSGS) occurs in a relevant proportion of FSGS patients and represents an important clinical emergency. It is taken as a proof of the existence of circulating permeability plasma factor(s) that are also putative effectors of original proteinuria in these patients. Familial forms of FSGS do not recur, but the discovery of numerous patients with sporadic FSGS and mutations of podocin (NPHS2, that is actually an inherited disease) who received a renal graft require a re-evaluation of the problem. Methods: To evaluate the incidence of posttransplant recurrence of FSGS in patients with NPHS2, the authors screened for podocin mutations in 53 patients with the clinical and pathologic stigmata of FSGS who had renal failure and who had undergone renal transplantation. Results. Twelve children were found to carry a homozygous (n9) or a heterozygous (n4) mutation of podocin and were classified, according to current criteria, as patients with inherited FSGS. In 5 patients of this group (38%), proteinuria recurred after renal graft and in 2, renal biopsy results showed recurrence of FSGS. Prerecurrence serum of 3 patients of this cohort was tested for antipodocin antibodies with indirect immuno-Western utilizing human podocyte extracts and were found negative. The rate of FSGS recurrence was comparable in non-NPHS2-FSGS children (12 of 27) and adults (3 of 13). Also clinical outcome of recurrence and response to plasmapheresis and immunosuppressors were comparable, suggesting a common mechanism. Conclusion: These data show a high rate of FSGS recurrence in patients with NPHS2 mutations that is comparable with idiopathic FSGS and describe the successful therapeutic approach. Recurrence of an apparently inherited disease should stimulate a critical review of the mechanisms of recurrence and of original proteinuria in these cases.

Original languageEnglish
Pages (from-to)1314-1321
Number of pages8
JournalAmerican Journal of Kidney Diseases
Volume41
Issue number6
DOIs
Publication statusPublished - Jun 1 2003

Keywords

  • Focal segmental glomerulosclerosis (FSGS)
  • Inherited glomerular disease
  • Podocin
  • Posttransplant recurrence of renal disease

ASJC Scopus subject areas

  • Nephrology

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    Bertelli, R., Ginevri, F., Caridi, G., Dagnino, M., Sandrini, S., Di Duca, M., Emma, F., Sanna-Cherchi, S., Scolari, F., Neri, T. M., Murer, L., Massella, L., Basile, G., Rizzoni, G., Perfumo, F., & Ghiggeri, G. M. (2003). Recurrence of focal segmental glomerulosclerosis after renal transplantation in patients with mutations of podocin. American Journal of Kidney Diseases, 41(6), 1314-1321. https://doi.org/10.1016/S0272-6386(03)00364-0