Factor V R506Q mutation (activated protein C resistance) is an additional risk factor for early renal graft loss associated with acute vascular rejection.

Abstract

The factor V R506Q mutation (FV R506Q, FV:Q506, or FV Leiden) resulting in activated protein C (APC) resistance is the most common inherited risk factor for venous thrombosis, including in renal transplant recipients. We investigated a possible association between the FV mutation and early renal graft loss, and the prevalence of macro- and microvascular thrombosis, endothelialitis, and fibrinoid vascular necrosis by FV genotype. One hundred and nine renal allograft recipients were genotyped for FV mutation. A vascular rejection subgroup of patients (n=29) had experienced at least one episode of vascular rejection, or graft thrombosis. A second group of patients (n=80) had experienced no acute rejection and retained a well-functioning graft. The prevalence of APC resistance was numerically but not statistically significantly higher in the vascular rejection group (17.2%) compared with the group without rejection episodes (7.5%) (P=0.16). There was a significant association between the presence or absence of FV mutation and graft survival, with a 55.6% 1-year graft survival rate versus a 76.4% rate, respectively (P=0.02). The prevalence of vascular rejection, as evidenced by endothelialitis or fibrinoid vascular necrosis, was significantly associated with APC resistance but macro- or microvascular thrombosis were not. Renal transplant recipients who are carriers of the FV:Q506 allele have an increased risk of early graft loss. Vascular rejection changes including endothelialitis and fibrinoid vascular necrosis were more common in this group, and therefore an association between the hypercoagulable state, which entails an up-regulation of the mitogenic and proinflammatory enzyme thrombin, and the immunological challenge to the endothelium may be the cause of inferior prognosis in these patients.