慢性移植肾肾病患者将环孢素A转换为他克莫司的临床观察

Conversion from cyclosporine to tacrolimus in patients with chronic allograft nephropathy

目的探讨慢性移植肾肾病(CAN)患者以他克莫司(FK506)替换环孢素A(CsA)的临床效果。方法根据是否以FK506来替换CsA,将97例诊断为CAN的患者分成两组,CsA组39例,维持原免疫抑制方案(CsA、霉酚酸酯和泼尼松联用)不变,采用替换方案的FK506组58例,除将CsA切换为FK506外,其它用药同CsA组。两组均随访1年以上,监测血胆固醇总量(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、尿素氮、肌酐、白蛋白及24h尿蛋白定量等生化指标的变化情况,观察随访期间药物的不良反应。结果CsA组的血脂水平无明显变化,而FK506组除HDL外,TC、LDL及TG等均较CsA组有不同程度的下降(P<0.05,P<0.01)。CsA组血肌酐继续上升,而FK506组的血肌酐下降,两组比较,差异有统计学意义(P<0.01);CsA组有3例移植肾功能丧失。FK506组需用降压药维持血压的例数少于CsA组(P<0.05);FK506组血清白蛋白水平显著高于CsA组(P<0.05),24h尿蛋白定量显著低于CsA组(P<0.01)。FK506组震颤发生率较CsA组高(P<0.01),而高血压、毛发增多及牙龈增生的发生率均显著低于CsA组(P<0.05)。结论CAN患者在以FK506替换CsA后,脂质代谢异常等到明显改善,肾功能减退得到延缓。

Objective To investigate and compare the effect of cyclosporine A （CsA） vs. tacrolimus （TAC） based immunosuppressive regimen on chronic allograft nephropathy. Methods Ninety-six patients who received a cadeveric kidney transplantation in our unit during Jan. 1995 to Jan. 2004 more than 12 months prior to study enrollment and who were being treated with CsA-based immunosuppressive treatment were included. All patients received allograft biopsy and were diagnosed as CAN. Patients were differentiated according to following regimen. Patients were either converted to tacrolimus （TAC group, u = 58） or remained on their initial CsA based immunosuppression （CsA group, n= 39）. The clinical data at study entry and after 3, 6 and 12 months including serum total cholesterol （TC）, triglyceride （TG）, low density lipoprotein （LDL）, high density lipoprotein （HDL）, blood urea nitrogen （BUN）, creatinine （SCr）, albumin were recorded during a follow up of over 12 months. Results Though TC, TG and LDL levels remained unchanged in CsA group, while statistically reduced in TAC group respectively （6.6±1.34 mmol/L vs. 5.20±0. 75 mmol/L, 3. 00 ± 1.40 mmol/L vs. 1.90 ± 0. 86 mmol/L, and 3. 70 ± 0. 93 mmol/L vs. 3. 00± 0. 72 mmol/L, P〈0. 01）. Quantity of daily urine protein excretion was significantly reduced and serum albumin levels were markedly elevated in the TAC group as compared with CsA group （ 1500 ± 700 mg/24 h vs 900±600mg/24h, P〈0.01, and 32.0±8.4 g/L vs. 45.0±10.2 g/L, P〈0.05）. Renal function was markedly improved, SCr was 150. 8 ± 53.4/μmol/L （P〈0. 01 ）, and less allograft failure was observed in the TAC group. Hypertension, hirsutism and gum hyperplasia were obviously decreased in the TAC group. Conclusion Tacrolimus treatment markedly improved abnormality in lipid profile post transplantation and graft renal function, and was excellent in the reduction of typical CsA-associated cosmetic side effects. Conversion from CsA to tacrolimus showed beneficial effects on the retardance of graft dysfunction.