肾移植后肝功能损害患者应用他克莫司替代环孢素A治疗18例

Tacrolimus instead of cyclosporine in 18 renal transplant recipients with hepatic impairment

目的:评价他克莫司替代环孢素A在肾移植后肝损害患者中治疗的有效性及安全性。方法:18例肾移植后肝功能损害的患者,男10例,女8例,年龄19～68岁,平均40岁,术前合并有糖尿病者2例,乙型肝者1例。术后均采用环孢素A6mg/(kg·d),术后1个月环孢素A质量浓度为250～400μg/L,半年内250μg/L,泼尼松按30mg/d,术后1个月改为20mg/d,术后霉酚酸酯为1.5g/d,或硫唑嘌呤50～100mg/d。当丙氨酸转氨酶>1500nkat/L,直接胆红素>25.1μmol/L,经保肝治疗,肝功能仍得不到改善时,即改用他克莫司,方法是停药后隔天开始服药,剂量0.1mg/(kg·d),随后根据药物浓度调整用量。霉酚酸酯及泼尼松用量不变。结果:18例患者均在15～60d内肝功能及胆红素代谢恢复正常,且没有排斥反应发生。1例肝炎患者转换前肝损害较重,恢复时间较长,为46d,有5例出现血糖升高,1例患者出现血脂高;血糖在(16.7±2.8)mmol/L。经降糖、降血脂治疗,血糖均控制在7.5mmol/L以下,血脂降至正常。结论:他克莫司替代环孢素A治疗肾移植术后肝损害效果较好,安全性也较高。

OBJECTIVE： To evaluate the efficacy and safety of tacrolimus （FK506） instead of cyclosporine （CsA） in renal transplant recipients with hepatic impairment. METHODS Eighteen patients with hepatic impairment, including 10 male and 8 females, aged 19-68 years （mean aged 40 years）, 2 out of them suffered diabetes mellitus, 1 of them had hepatitis B prior to operation. After operation, all patients were treated with CsA 6 mg/（kgod）, the mass concentration was changed from 250-400 μg/L at 1 month after operation to 250 μg/L after half year. Totally 30 mg/d prednisone was used at first and changed to 20 mg/d at 1 month after operation. Mycophenolate was applied with 1.5 g/d, or azothioprine 50 100 mg/d. FK506 was used instead of CsA when alanine aminotransferase was over 1 500 nkat/L, with over 25.1 pmol/L bilirubin direct. The initial dose of FK506 was 0.1 mg/（kg · d） at the second day after drug withdrawal and adjusted to base on its blood trough levels and the degree of hepatic impairment. The dosage of mycophenolate or prednisone was invariably. RESULTS Hepatic function and bilirubin metabolism of all patients were returned to normal leverl without reject reaction in 15-60 days. One patient, who had severe hepatic impairment, was recovered in 46 days. Five patients had high blood sugar levels, and one had high blood cholesterol. After hypoglycemic and cholesterol lowering therapy, the blood glucose was controlled below 7.5 mmol/L from at the beginning of （16.7±2.8） mmol/L, and the blood fat was kept in a normal level. CONCLUSION： FK506 substituting for CsA can recover hepatic function with high safety in recipients with hepatic impairment.