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. Conclusion. 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.