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NDT Advance Access first published online on May 7, 2008
This version published online on May 27, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn241
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


PAI-1 donor polymorphism influences long-term kidney graft survival

Jean-Philippe Rérolle1, Elisa Munteanu1,2, Mireille Drouet2, Jean-Christophe Szelag1, Béatrice Champtiaux1, Fatima Yagoubi1, Pierre-Marie Preux3, Jean-Claude Aldigier1 and Yann Le Meur1

1 Transplantation 2 Immunology 3 Biostatistic units, CHU Dupuytren, Limoges, France

Correspondence and offprint requests to: Rerolle Jean-Philippe, Service de transplantation rénale, CHU Dupuytren, 2 Avenue Martin Luther King, 87000 Limoges, France. Tel: +33-5-55056464; Fax: +33-5-55055432; E-mail: jean-philippe.rerolle{at}chu-limoges.fr



  Abstract

Background. The type 1 plasminogen activator inhibitor (PAI-1) is involved in the development of fibrosis, and its intrarenal expression is increased in interstitial fibrosis and tubular atrophy (IFTA). Moreover, a 4G/5G polymorphism of the PAI-1 gene has been described associating 4G haplotype with higher PAI-1 plasma activity. We investigated the relationship between the donor and recipient PAI-1 polymorphism and kidney graft survival.

Methods. The PAI-1 genotype was determined for both the 304 donors and the 337 corresponding recipients. In recipients, PAI-1 antigen levels were also determined. We compared 4G/4G donors versus donors with other genotypes.

Results. Donor or recipient genotype did not influence the PAI-1 plasma level in recipients. Actuarial kidney graft survival was significantly reduced in the 4G/4G donor group (107 months versus 147.5 months, P = 0.013), while recipient PAI-1 genotype did not show any influence on graft survival. Moreover, graft loss due to IFTA proved significantly higher in the 4G/4G donor group (13% versus 6%, P = 0.03). Multivariate analysis showed that the significant independent variables associated with graft loss were the donor 4G/4G genotype, acute clinical rejection and donor age.

Conclusion. Our study suggests that donor PAI-1 polymorphism influences kidney graft survival and that the donor 4G/4G genotype is an independent risk factor for graft loss. Prospective studies are needed to confirm these results.

Keywords: chronic allograft nephropathy; gene polymorphism; PAI-1; renal transplantation

Received for publication: 19.10.07
Accepted in revised form: 7. 4.08


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