Chronic graft dysfunction in renal transplant patients: potential role of plasminogen activator inhibitor type 1.
BACKGROUND
Chronic allograft nephropathy is the main cause of long-term kidney graft loss. The plasminogen activator inhibitor type 1 (PAI-1) is a potential fibrogenic molecule whose secretion is regulated by several metabolic, inflammatory, and genetic factors. We aimed to determine whether PAI-1 secretion in renal transplant patients is correlated with the decline in renal function after transplantation.


METHODS
Renal transplant patients (145 male/71 female) were included in the study 1-27 years after transplantation (median of follow-up: 7.35 years). At inclusion, routine clinical and biological data were collected, the 4G/5G polymorphism of the recipient PAI-1 gene was determined, and the PAI-1 plasma level was measured.


RESULTS
The mean rate of decline in renal function was -4.26+/-0.30 ml/min/year. By multiple linear regression analysis, the rate of decline in renal function was significantly correlated with proteinuria (P=0.0176), occurrence of late acute rejection episodes (P=0.0001), and PAI-1 plasma level (P=0.0051). In addition, PAI-1 plasma level was also significantly correlated with body mass index (P=0.038), insulin (P<0.0001), platelet count (P<0.0001), and fibrinogen (P=0.024). The PAI-1 gene polymorphism tested did not influence the rate of decline in renal function after transplantation nor the plasma level of PAI-1 antigen.


CONCLUSIONS
We conclude that PAI-1, whose secretion is determined in large part by metabolic and inflammatory factors, may be implicated in the rate of decline in renal function after transplantation.
Lahlou
Anis
A
Service de Néphrologie A, Association Claude Bernard and INSERM U 489, Hôpital Tenon, Paris, France.
Peraldi
Marie-Noëlle
MN
Thervet
Eric
E
Flahault
Antoine
A
Delarue
Françoise
F
Soubrier
Florent
F
Rossert
Jérôme
J
Hertig
Alexandre
A
Rondeau
Eric
E
D000328:Adult; D000483:Alleles; D001483:Base Sequence; D003404:Creatinine / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000503:physiopathology*; D013997:Time Factors
D017395:Plasminogen Activator Inhibitor 1; D003404:Creatinine