Irish A B, Thompson C H
Oxford Renal Unit, Churchill Hospital, Headington, Oxford, UK.
Nephrol Dial Transplant. 1996 Nov;11(11):2223-8. doi: 10.1093/oxfordjournals.ndt.a027140.
The dyslipidaemia of chronic renal disease could contribute to a hypercoagulable state by activation of blood coagulation and/or impairment of fibrinolysis, thereby increasing cardiovascular disease (CVD) risk.
We measured the coagulation activation marker prothrombin fragment F1 + 2 (F1 + 2), fibrinogen, plasminogen activator inhibitor-1 activity (PAI1), interleukin-6 (IL6), insulin, lipids and lipoprotein(a) (Lp(a)), in 12 patients with chronic renal disease before and after gemfibrozil.
Gemfibrozil significantly reduced triglycerides by 44% and increased HDL-cholesterol by 31% without significant change in LDL cholesterol. Before treatment, patients had increased F1 + 2, fibrinogen and IL6, but similar PAI1 compared with the controls, consistent with a hypercoagulable and persistent inflammatory state. Following treatment, F1 + 2 decreased to within the normal range and this reduction correlated with the decrease in triglycerides and inversely with the increase in HDL-cholesterol. A non-significant decrease in fibrinogen was inversely correlated with a significant increase in albumin. However, Lp(a) and PAI1 activity significantly increased whilst insulin and IL6 were unchanged.
Gemfibrozil improved the uraemic dyslipidaemia and hypercoagulable state by reduction in activation of blood coagulation, indirectly suggesting a reduction in lipid-dependent extrinsic pathway activity which should contribute to reduced risk of thrombosis and CVD. Reduced fibrinogen and increased albumin are consistent with a reduction in the acute phase response. Increased PAI1 and Lp(a) could impair fibrinolysis and potentially increase CVD risk, although the mechanism for these effects is uncertain but does not appear related to cytokine or insulin mediated mechanisms and requires further study. Large prospective studies are required to determine if gemfibrozil can reduce CVD events in uraemia.
慢性肾病的血脂异常可通过激活凝血和/或纤溶功能受损导致高凝状态，从而增加心血管疾病（CVD）风险。
我们测定了12例慢性肾病患者在服用吉非贝齐前后的凝血激活标志物凝血酶原片段F1 + 2（F1 + 2）、纤维蛋白原、纤溶酶原激活物抑制剂-1活性（PAI1）、白细胞介素-6（IL6）、胰岛素、血脂和脂蛋白（a）（Lp（a））。
吉非贝齐显著降低甘油三酯44%，升高高密度脂蛋白胆固醇31%，而低密度脂蛋白胆固醇无显著变化。治疗前，患者的F1 + 2、纤维蛋白原和IL6升高，但与对照组相比PAI1相似，这与高凝和持续炎症状态一致。治疗后，F1 + 2降至正常范围内，这种降低与甘油三酯的降低相关，与高密度脂蛋白胆固醇的升高呈负相关。纤维蛋白原的非显著降低与白蛋白的显著升高呈负相关。然而，Lp（a）和PAI1活性显著升高，而胰岛素和IL6无变化。
吉非贝齐通过降低凝血激活改善了尿毒症血脂异常和高凝状态，间接提示脂质依赖性外源性途径活性降低，这应有助于降低血栓形成和CVD风险。纤维蛋白原降低和白蛋白升高与急性期反应的降低一致。PAI1和Lp（a）升高可能会损害纤溶功能并可能增加CVD风险，尽管这些作用的机制尚不确定，但似乎与细胞因子或胰岛素介导的机制无关，需要进一步研究。需要进行大型前瞻性研究来确定吉非贝齐是否能降低尿毒症患者的CVD事件。
