ENVIRONMENTAL AND GENETIC-DETERMINANTS OF THE HYPERCOAGULABLE STATE AND CARDIOVASCULAR-DISEASE IN RENAL-TRANSPLANT RECIPIENTS

Background. Fibrinogen and factor VII coagulant activity (VIIc), risk factors for cardiovascular disease (CVD) in the general population, co uld contribute to CVD risk in renal transplant recipients (RTR). Metho ds. We measured fibrinogen and VIIc in 38 RTR and 31 controls, along w ith prothrombin fragment F1 + 2 and D-Dimer (markers of coagulation an d fibrinolytic activation), plasma lipids and the acute phase response cytokine, interleukin 6. The effect of genetic polymorphisms of beta- fibrinogen (G/A(-455)) and factor VII (Arg/Gln(353)) was explored. Res ults. F1 + 2, D-Dimer, and fibrinogen were increased in all RTR, indic ating a chronic prothrombotic state. Fibrinogen correlated with age, F 1 + 2, and trough cyclosporin A (CsA). RTR carriers of the A(-455) all ele had greater increment in plasma fibrinogen concentration and corre lation with CsA than homozygotes for the G(-455) allele. Interleukin 6 was increased in RTR confirming that a persistent low-grade acute-pha se response could contribute to increased fibrinogen. Differences in p lasma VIIc were associated with factor VII genotype, disease status, a nd blood lipids. Carriers of the Gln(353) allele had 30% lower VIIc wh en compared with Arg(353) homozygotes, which could confer a reduced th rombotic risk. The 12 RTR with CVD or metabolic complications (RTR+) w ere more hyperlipidaemic and had higher fibrinogen and VIIc than the 2 6 RTR free of disease complications (RTR-), or the controls. Conclusio ns. Long-term RTR manifest features of a chronic prothrombotic and per sistent inflammatory state. Alterations in fibrinogen and VIIc in RTR arise in part as a result of interactions between common genetic and e nvironmental factors, and these changes could contribute to the increa sed risk of CVD in RTR.