他克莫司替换环孢素A治疗早期慢性移植肾肾病的疗效评估

Evaluating the curative effect of conversion from cyclosporine A to tacrolimus on chronic allograft nephropathy

目的:实践证明他克莫司不仅比环孢素A肾毒性较小,而且可以降低心血管风险,还能提高肾移植受者的内生肌酐清除率来改善移植肾功能。观察用他克莫司替代环孢素A减缓早期慢性移植肾肾病患者肾功能衰竭的速度,并分析其可能机制。方法:①实验对象:选择2003-03/2006-04解放军第三军医大学大坪医院收治的正在服用环孢素A的慢性移植肾肾病早期患者64例,对实验及治疗方案均知情同意。②实验方法及分组:按用药情况分为2组,他克莫司组(n=31)将环孢素A改为他克莫司,剂量为0.15～0.3mg/(kg·d),其他免疫抑制剂不变;环孢素A组(n=33)环孢素A和其他免疫抑制剂均不作调整。③实验评估:分别于药物方案调整前、调整12,36个月后监测两组患者的血肌酐、血脂及抗高血压评分,抗高血压评分分数越高代表应用的抗高血压药物强度越大。结果:64例患者全部进入结果分析。①血肌酐水平:药物调整12个月后,他克莫司组血肌酐水平显著低于调整前(P<0.01);调整12,36个月后,环孢素A组血肌酐水平均显著高于调整前(P<0.01)。与环孢素A组相比,他克莫司组血肌酐水平在调整12,36个月后明显降低(P=0.011,0.046)。②抗高血压评分:药物调整12,36个月后,他克莫司组均显著低于环孢素A组(P<0.01)。③血脂水平:药物调整12个月后,他克莫司组低密度脂蛋白胆固醇水平显著低于环孢素A组(P<0.01)。结论:当肾移植患者出现慢性移植肾肾病时,将主要免疫抑制剂由环孢素A转换为他克莫司可以改善肾移植受者的肾功能,降低低密度脂蛋白胆固醇水平,并可减缓慢性移植肾肾病的进展,有助于提高移植肾的长期存活率。

AIM: Tacrolimus has been proved to reduce risk of cardiovascular disease, increase creatinine clearance rate of kidney transplant recipients and improve function of the renal kidney, thus it is superior to cyclosporine A (CSA). This study was conducted to investigate the effect of the conversion from CSA to tacrolimus on ameliorating the progression of renal dysfunction in kidney transplant recipients with chronic allograft nephropathy, and analyze the possible mechanism. METHODS: ①Totally 64 patients with chronic allograft nephropathy were enrolled from the Daping Hospital in the Third Military Medical University of Chinese PLA between March 2003 and April 2006. Informed consents of experiments and treatments were obtained from all the patients, who had been treated with CSA.②Of the 64 patients, 31 were converted from CSA to tacrolimus (0.15-0.3 mg/kg per day), whereas other 33 patients were maintained on CSA. Other immune depressants were not changed in two groups.③Serum creatinine, lipid profiles and antihypertensive score were determined before conversion and 12, 36 months after conversion. Higher antihypertensive score indicated stronger intensity of antihypertensive medications. RESULTS: All of 64 patients were involved in the result analysis.①Serum creatinine in the tacrolimus group was decreased after 12 months compared with that before conversion (P < 0.01); whereas a significant increase in serum creatinine was detected in CSA group after 12 and 36 months (P < 0.01), and compared to CSA therapy, serum creatinine in the tacrolimus group declined obviously (P =0.011, 0.046).②Antihypertensive score of the tacrolimus group was significantly lower than that in the CSA group after 12 and 36 months (P < 0.01).③Compared with CSA group, low density lipoprotein cholesterol was significantly lower in the tacrolimus group after 12 months (P < 0.001). CONCLUSION: Conversion from CSA to tacrolimus in kidney transplant recipients with chronic allograft nephropathy can improve allograft function, reduce low density lipoprotein cholesterol, and ameliorate progression of chronic allograft nephropathy. This superior profile may contribute to improve long-term graft survival.