Increased rate of renal transplant failure in patients with the G20210A mutation of the prothrombin gene

In patients with thrombophilia caused by reduced physiological anticoagulat ion, renal transplant failure occurs more frequently. Previous studies show ed the importance of the protein C system, a physiological anticoagulatory pathway that inhibits thrombus formation. However, excess activation of the hemostatic system also may result in thrombosis. The G20210A mutation in t he prothrombin gene is such a prothrombotic risk factor that results in inc reased thrombus formation because of elevated factor II levels in plasma. W e analyzed graft function in 270 consecutive patients who received 311 rena l transplants. The presence of a normal or mutated prothrombin allele was d etermined by polymerase chain reaction amplification and restriction fragme nt length polymorphism analysis of genomic DNA. Demographic data were extra cted from hospital records, Graft survival was calculated for patients with and without the G20210A mutation. We identified 9 patients heterozygous fo r the G20210A mutation in the prothrombin gene who had received a total of 12 renal transplants, Of these 12 transplants, 2 grafts were lost within th e first year. Median graft survival for patients heterozygous for the 20210 A allele was 65.9 months (range, 0 to 101 months) compared with 149 months (range, 0 to 237 months) for patients homozygous for the normal 20210G alle le (P = 0.02). The G20210A mutation represented a 2.95-fold (95% confidence interval, 1.03 to 8.46) increase in risk for graft loss. Only 1 patient wi th this mutation achieved graft function exceeding 101 months. The G20210A mutation of the prothrombin gene is an independent risk factor for graft fa ilure. (C) 2001 by the National Kidney Foundation, Inc.