A B Irish1, F R Green. 1. Oxford Renal Unit, Churchill Hospital, Oxford, UK.
Abstract
BACKGROUND: Fibrinogen and factor VII coagulant activity (VIIc), risk factors for cardiovascular disease (CVD) in the general population, could contribute to CVD risk in renal transplant recipients (RTR). METHODS: We measured fibrinogen and VIIc in 38 RTR and 31 controls, along with prothrombin fragment F1 + 2 and D-Dimer (markers of coagulation and 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/Gln353) was explored. RESULTS: F1 + 2, D-Dimer, and fibrinogen were increased in all RTR, indicating a chronic prothrombotic state. Fibrinogen correlated with age. F1 + 2, and trough cyclosporin A (CsA). RTR carriers of the A-455 allele had a greater increment in plasma fibrinogen concentration and correlation with CsA than homozygotes for the G-455 allele. Interleukin 6 was increased in RTR confirming that a persistent lowgrade acute-phase response could contribute to increased fibrinogen. Differences in plasma VIIc were associated with factor VII genotype, disease status, and blood lipids. Carriers of the Gln353 allele had 30% lower VIIc when compared with Arg353 homozygotes, which could confer a reduced thrombotic risk. The 12 RTR with CVD or metabolic complications (RTR+) were more hyperlipidaemic and had higher fibrinogen and VIIc than the 26 RTR free of disease complications (RTR-), or the controls. CONCLUSIONS: Long-term RTR manifest features of a chronic prothrombotic and persistent inflammatory state. Alterations in fibrinogen and VIIc in RTR arise in part as a result of interactions between common genetic and environmental factors, and these changes could contribute to the increased risk of CVD in RTR.
BACKGROUND:Fibrinogen and factor VII coagulant activity (VIIc), risk factors for cardiovascular disease (CVD) in the general population, could contribute to CVD risk in renal transplant recipients (RTR). METHODS: We measured fibrinogen and VIIc in 38 RTR and 31 controls, along with prothrombin fragment F1 + 2 and D-Dimer (markers of coagulation and 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/Gln353) was explored. RESULTS: F1 + 2, D-Dimer, and fibrinogen were increased in all RTR, indicating a chronic prothrombotic state. Fibrinogen correlated with age. F1 + 2, and trough cyclosporin A (CsA). RTR carriers of the A-455 allele had a greater increment in plasma fibrinogen concentration and correlation with CsA than homozygotes for the G-455 allele. Interleukin 6 was increased in RTR confirming that a persistent lowgrade acute-phase response could contribute to increased fibrinogen. Differences in plasma VIIc were associated with factor VII genotype, disease status, and blood lipids. Carriers of the Gln353 allele had 30% lower VIIc when compared with Arg353 homozygotes, which could confer a reduced thrombotic risk. The 12 RTR with CVD or metabolic complications (RTR+) were more hyperlipidaemic and had higher fibrinogen and VIIc than the 26 RTR free of disease complications (RTR-), or the controls. CONCLUSIONS: Long-term RTR manifest features of a chronic prothrombotic and persistent inflammatory state. Alterations in fibrinogen and VIIc in RTR arise in part as a result of interactions between common genetic and environmental factors, and these changes could contribute to the increased risk of CVD in RTR.