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

Background. The factor V R506Q mutation (FV R(506)Q, FV:Q(506), Or FV Leide n) resulting in activated protein C (APC) resistance is the most common inh erited risk factor for venous thrombosis, including in renal transplant rec ipients. We investigated a possible association between the FV mutation and early renal graft loss, and the prevalence of macro- and microvascular thr ombosis, endothelialitis, and fibrinoid vascular necrosis by FV genotype. Method One hundred and nine renal allograft recipients were genotyped for F V mutation. A vascular rejection subgroup of patients (n=29) had experience d 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. Results. The prevalence of APC resistance was numerically but not statistic ally significantly higher in the vascular rejection group (17.2%) compared with the group without rejection episodes (7.5%) (P=0.16). There was a sign ificant association between the presence or absence of FV mutation and graf t survival, with a 55.6% 1-year graft survival rate versus a 76.4% rate, re spectively (P= 0.02). The prevalence of vascular rejection, as evidenced by endothelialitis or fibrinoid vascular necrosis, was significantly associat ed with APC resistance but macro- or microvascular thrombosis were not. Conclusion, Renal. transplant recipients who are carriers of the FV:Q(506) allele have an increased risk of early graft loss. Vascular rejection chang es including endothelialitis and fibrinoid vascular necrosis were more comm on 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.