Outcome of kidney transplantation in patients with inherited thrombophilia: data of a prospective study.
Inherited prothrombotic risk factors predispose patients to thromboembolic events. In kidney transplant recipients, thrombophilia may manifest itself with venous thrombosis, microvascular occlusion, or acute rejection with major consequences for allograft survival. This is a prospective study on 165 renal allograft recipients to evaluate the contribution of genetic thrombophilic risk factors to transplant outcome. Besides antithrombin, protein C, and protein S deficiencies, none of which was found in our patient group, factor V G1691A (FV G1691A), prothrombin G20210A (PT G20210A) mutations, and methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms were studied. The primary endpoint of the study was occurrence of an acute rejection within the first 90 d and transplant loss within 1 yr. Heterozygous FV G1691A and PT G20210A mutations and the MTHFR T677T variant were significantly associated with acute rejections with rejection rates of 68%, 67%, and 71%, respectively, as compared with 35% in patients not carrying these genotypes. Many rejections that were histologically proven were acute vascular ones. Transplant loss was significantly associated exclusively with the PT G20210A group (50% 1-yr graft survival; odds ratio, 10.0; 95% confidence interval, 1.8 to 56.1). PT G20210A patients exerted the highest prothrombotic activity pretransplant, as determined by prothrombin 1.2 fragments (PT F1.2), which may be the background for minor outcome. In conclusion, common prothrombotic mutations are significantly associated with acute rejections, especially vascular rejections, and for PT G20210A also with early transplant failure. Screening for hypercoagulable states pretransplant is recommended to intensify anticoagulatory treatment posttransplant.
Heidenreich
Stefan
S
Department of Medicine, University of Münster, Germany. heidenr@uni-muenster.de
Junker
Ralf
R
Wolters
Heiner
H
Lang
Detlef
D
Hessing
Sabine
S
Nitsche
Gitta
G
Nowak-Göttl
Ulrike
U
D000328:Adult; D005165:Factor V / Q000235:genetics; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000209:etiology; D006085:Graft Survival; D006579:Heterozygote; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D017354:Point Mutation; D011446:Prospective Studies; D011516:Prothrombin / Q000235:genetics; D019851:Thrombophilia / Q000150:complications / Q000235:genetics*; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)