Schrama Y C, Hené R J, de Jonge N, Joles J A, Van Rijn H J, Bär D R, Ververs T F, Van Tol A, Koomans H A
Department of Nephrology, University Hospital Utrecht, The Netherlands.
Transplantation. 1998 Nov 15;66(9):1175-81. doi: 10.1097/00007890-199811150-00011.
Dyslipidemia is found in the majority of renal and cardiac transplant recipients. Although 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors significantly lower low-density lipoprotein cholesterol (LDL-C) levels, such treatment has been associated with muscle toxicity, especially when used in combination with cyclosporine (CsA). We investigated the efficacy and muscle safety of fluvastatin, a new 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, in CsA-treated transplant recipients.
The efficacy was determined by measuring the lipid profile before and after 8 weeks of fluvastatin therapy. As parameter for possible muscle damage, the rise in serum levels of the muscle proteins creatine kinase and myoglobin was measured after an exercise provocation test (30 min on a bicycle ergometer at 60% of their maximal work load) before and during fluvastatin therapy. Nineteen CsA-treated renal and cardiac transplant recipients with hypercholesterolemia were selected.
After 8 weeks of treatment with a dose of fluvastatin necessary to reduce LDL-C below 3.5 mmol/L (20 mg for 3 and 40 mg for 16 patients), total cholesterol was lowered by 20% and LDL-C by 30%, and HDL2-C was increased by 35% (all P<0.01). The rise in creatine kinase after exercise before and during fluvastatin therapy was, respectively, 40% and 51%, and the rise in myoglobin was 64% and 50%. These rises were not significantly different. Hence, there was no indication for subclinical muscle pathology by fluvastatin use. Fluvastatin was well tolerated, and no adverse effects on liver or kidney function were found.
Fluvastatin can effectively lower LDL-C in CsA-treated renal and cardiac transplant recipients, without demonstrable adverse effects.
大多数肾移植和心脏移植受者存在血脂异常。尽管3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂能显著降低低密度脂蛋白胆固醇（LDL-C）水平，但这种治疗与肌肉毒性有关，尤其是与环孢素（CsA）联合使用时。我们研究了新型3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂氟伐他汀在接受CsA治疗的移植受者中的疗效和肌肉安全性。
通过测量氟伐他汀治疗8周前后的血脂谱来确定疗效。作为可能肌肉损伤的参数，在氟伐他汀治疗前和治疗期间进行运动激发试验（在自行车测力计上以最大工作负荷的60%骑行30分钟）后，测量肌肉蛋白肌酸激酶和肌红蛋白的血清水平升高情况。选择了19例接受CsA治疗的高胆固醇血症肾移植和心脏移植受者。
用将LDL-C降至3.5 mmol/L以下所需剂量的氟伐他汀治疗8周后（3例患者用20 mg，16例患者用40 mg），总胆固醇降低了20%，LDL-C降低了30%，HDL2-C升高了35%（均P<0.01）。氟伐他汀治疗前和治疗期间运动后肌酸激酶的升高分别为40%和51%，肌红蛋白的升高为64%和50%。这些升高无显著差异。因此，没有迹象表明使用氟伐他汀会导致亚临床肌肉病变。氟伐他汀耐受性良好，未发现对肝肾功能有不良影响。
氟伐他汀能有效降低接受CsA治疗的肾移植和心脏移植受者的LDL-C，且无明显不良反应。
