High rate of acute rejections in renal allograft recipients with thrombophilic risk factors

Abstract

Inherited and acquired thrombophilic disorders predispose patients for thromboembolic and probably other occlusive vascular events that occur when additional risk factors play in concert. Because acute rejections in renal transplant recipients may reflect vascular events, and an impairment of the fibrinolytic system in immunosuppressed patients has been previously described, the implications of genetic or acquired risk factors of thrombophilia for the occurrence of early acute rejections after kidney transplantation were evaluated. The following risk factors of thrombophilia were determined in 97 patients after cadaveric kidney transplantation: factor V Leiden mutation, protein S, protein C, and antithrombin deficiency. In a retrospective analysis, the prevalence of acute rejections, the histologic classification when rejection episodes had been confirmed by biopsy, and other vascular complications were evaluated. In 21 of the 97 patients, an inherited or acquired risk factor of thrombophilia was detected. Prevalence of acute rejections was 71% in the first 6 mo after transplantation in patients with a thrombophilic disorder and significantly higher compared with patients without thrombophilia (41%; P = 0.017). The distribution of classic risk factors associated with acute rejections, such as number of human leukocyte antigen mismatches or percentage of panel-reactive antibodies, was similar in patients with and without thrombophilia. In the eight patients with thrombophilia and histologically proven acute rejection, four patients had an acute vascular rejection, and in two patients a vascular involvement was suspected. Furthermore, prevalence of cerebral or coronary vascular disease, or venous thromboembolic complications, was significantly higher in patients with a thrombophilic clotting defect (67%) compared with patients with normal hemostasis parameters (28%; P < 0.002). It is concluded that renal allograft recipients with thrombophilia are at risk of developing an acute rejection or other vascular event. Although the determination of thrombotic risk factors was performed at least 3 mo after an acute rejection episode, it can be presumed that acute rejection episodes are associated with subsequent coagulatory abnormalities with further consequences for transplant survival. Thus, pretransplant evaluation of genetic and acquired risk factors of thrombophilia is recommended.