IFN-g polymorphism and its impact on delayed graft function of kidney allografts.

Abstract

165 Delayed Graft Function (DGF) is a strong predictor of long term outcome of cadaveric renal allografts. Although long Cold Ischaemic Time (CIT) is positively related to a higher incidence of DGF there are other unexplained factors that might play a role. IFN-γ is known to promote nitric oxide synthase and therefore nitric oxide (NO) production. Nitric oxide plays a protective role in ischaemic reperfusion injury. This study was designed to investigate the role of IFN-γ genotype in DGF. We analysed specimens from 88 first kidney transplants for the existence of a polymorphism (allele #2) that we have previously described in the gene of IFN-γ. The existence of this allele, which comprises of 12 CA repeats, is positively correlated with higher production of IFN-γ in vitro. We compared the two group of patients (expressing and not expressing allele #2) for the incidence of DGF. Half of these patients were on cyclosporine monotherapy. Results: There were 70 patients expressing allele #2 (group A) and 18 not expressing it (group B). Characteristics of the two groups are shown in table 1.Table 1The causes of death (CVA vs. trauma) and the incidence of hypotention prior to donation were also similar between the two groups. Delayed Graft Function was seen in 21.4% of patients in group A (high IFN-γ producers) as opposed to 38.9% of patients in group B (p=0.08). DGF was an important independent predictor of graft survival and graft function 7 years post-transplant. Despite its effect on DGF the absence of allele #2 was correlated with better kidney function 5 years post-transplant. Conclusion: The existence of a polymorphic allele in the gene of IFN-γ, which is associated with higher in vitro production of this cytokine, reduces the incidence of DGF in renal allografts, even when the impact of CIT, initial immunosuppressive treatment and cause of donor death, are taken into account. This is probably due to the induction by IFN-γ of nitric oxide synthase that plays a protective role in ischaemic reperfusion injury.