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


CONCLUSIONS
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.
Rérolle
Jean-Philippe
JP
Service de transplantation rénale, CHU Dupuytren, 2 Avenue Martin Luther King, 87000 Limoges, France. jean-philippe.rerolle@chu-limoges.fr
Munteanu
Elisa
E
Drouet
Mireille
M
Szelag
Jean-Christophe
JC
Champtiaux
Béatrice
B
Yagoubi
Fatima
F
Preux
Pierre-Marie
PM
Aldigier
Jean-Claude
JC
Le Meur
Yann
Y
D000328:Adult; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005838:Genotype; D006085:Graft Survival / Q000235:genetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000235:genetics / Q000601:surgery; D016030:Kidney Transplantation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013997:Time Factors; D014019:Tissue Donors; D055815:Young Adult
D017931:DNA Primers; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human