他克莫司替换环孢素A对慢性移植肾肾病进展的影响☆

Abstract

BACKGROUND:The introduction of cyclosporin A (CsA) has greatly enhanced the early survival rate of kidney graft, but the long-term graft survival rate is still limited. Whether tacrolimus prevents chronic allograft nephropathy (CAN) and prolongs survival time is now becoming a hot spot in field of renal transplantation.

OBJECTIVE: To investigate the feasibility and safety of converting CsA to tacrolimus (FK506) in preventing progression of CAN.

DESIGN: Observation and controlled trial.

SETTING: Department of Urological Organ Transplantation, Center of Organ Transplantation, the Second Xiangya Hospital, Central South University.

PARTICIPANTS: A total of 73 patients who had received kidney transplantation at the Department of Urological Organ Transplantation, Center of Organ Transplantation, the Second Xiangya Hospital of Central South University from April 2001 to October 2005, and had been diagnosed as CAN by graft biopsy (42 male patients and 31 female patients; age ranged 19–69 years), were enrolled in the study approved by the ethics committee of this hospital after their written informed consents. CsA soft capsules (Hangzhou Zhongmei Huadong Pharmaceutical Limited Company or Huabei Pharmaceutical Limited Company); mycophenolate mofetil capsules (Shanghai Roche Pharmaceutical Limited Company); prednisone acetate tablets (Second Xiangya Hospital of Central South University); tacrolimus capsules (Fujisawa Pharmaceutical Limited Company).

METHODS: Seventy-three patients voluntarily participated in CsA group (n =30) or FK506 group (n =43). The two groups were homogenous regarding patients’ sex, age and general data (P > 0.05). Patients in the CsA group were continued on their initial immunosuppression protocol, which consisted of CsA, mycophenolate mofetil and prednisone acetate. In the FK506 group, CsA was stopped, and FK506 was started at a dose of 0.08–0.1 mg/(kg·d) 24 hours later, twice daily, administered 2 hours after breakfast and supper. Three days later, the blood trough concentration of FK506 was tested and adjusted to a target range of 5–8μg/L. FK506 dosage adjustment was based on the blood trough concentration, serum creatinine (SCr) and its side effects. All 73 patients were treated for 12 months.

MAIN OUTCOME MEASURES: SCr, glomerular filtration rate (GFR), 24-hour urine protein excretion, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL) and the toxic side effects of calcineurin inhibitors (incidences of tremor, hyperglycemia and hypertension) were monitored during a follow-up of over 12 months.

RESULTS: A total of 73 patients were involved in the result analysis.①12 months after conversion, the level of SCr was statistically reduced and GFR levels were markedly elevated in the FK506 group compared with the CsA group (P < 0.01). TC, TG and LDL levels in the FK506 group were significantly lower than those in the CsA group (P < 0.01).②Compared with the CsA group, the incidence of tremor was obviously increased [30% (9/30), 5% (2/43), P < 0.01] and the incidence of hypertension was obviously decreased [56% (24/43), 83% (25/30), P < 0.05] in the FK506 group.

CONCLUSION: Conversion from CsA to FK506 can postpone renal dysfunction, reduce proteinuria and improve hyperlipidemia. FK506 treatment is an effective therapy in slowing the progression of CAN.

Xie Xu-biao☆, Doctor, Associate professor, Depart-ment of Urological Organ Transplanta-tion, Center of Organ Transplantation, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
xiexubiao@yahoo.
com.cn

Received:2007-10-20
Accepted:2007-11-08
(07-50-10-5682/YWY)

Xie XB, Peng LK, Peng FH, Yu SJ, Wang Y, Jiang Y, Lan GB, Fang CH, Nie MH. Influence of conversion from cyclosporin A to tacrolimus on chronic allograft nephropa-thy.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(5):979-982
(China)
[www.zglckf.com/zglckf/ejournal/upfiles/08-5/5k-979
(ps).pdf]

摘要
背景：环孢素A的应用显著提高了移植肾的早期存活率，但远期移植物失功并未得到明显改善。他克莫司能否延缓慢性移植肾肾病进展，从而延长移植物的存活时间？
目的：观察他克莫司替换环孢素A治疗慢性移植肾肾病的有效性及安全性。
设计：观察对比实验。
单位：中南大学湘雅二医院器官移植中心泌外器官移植科。
对象：选择2001–04/2005–10在中南大学湘雅二医院器官移植中心泌外器官移植科接受同种异体肾移植术后发生慢性移植肾肾病的73例患者，均经移植肾穿刺活检证实。男42例，女31例，年龄19~69岁，所有患者均对治疗项目知情同意，实验经过医院伦理委员会批准许可。环孢素A软胶囊为杭州中美华东制药有限公司或华北制药有限公司产品，吗替麦考酚酸酯胶囊购自上海罗氏制药有限公司，醋酸泼尼松片为中南大学湘雅二医院提供，他克莫司胶囊为藤泽药品中国有限公司产品。
方法：根据患者治疗意愿将患者分为环孢素A组（n =30）和他克莫司组（n =43），两组患者性别、年龄及一般情况差异无统计学意义（P > 0.05）。环孢素A组患者维持原免疫抑制方案进行治疗，即环孢素A、霉酚酸酯及泼尼松联用。他克莫司组将环孢素A转换成他克莫司， 他克莫司转换方案为停服环孢素A 24 h后开始服用他克莫司，其起始剂量为0.08~0.1 mg/（kg·d），早晚餐后2 h口服，服药3 d后测其谷值浓度，要求其血药浓度维持在5~8μg/L，并根据血药浓度、血清肌酐及其毒副作用调整剂量，其他用药同环孢素A组，两组均治疗12个月。
主要观察指标：①治疗12个月后监测两组患者血清肌酐、肾小球滤过率、24 h尿蛋白定量、血脂（包括总胆固醇、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇等生化指标）变化情况；②观察药物毒副作用（震颤、高血糖及高血压等发生情况）。
结果：患者73例均进入结果分析。①生化指标检测结果：转换治疗12个月后，他克莫司组血清肌酐及24 h尿蛋白定量显著低于环孢素A组，差异有统计学意义(P < 0.01)；肾小球滤过率显著高于环孢素A组，差异有统计学意义（P < 0.01）；总胆固醇、三酰甘油、低密度脂蛋白胆固醇均显著低于环孢素A组，差异有统计学意义（P < 0.01）。②毒副作用：他克莫司组震颤发生率为，高于环孢素A组[30% (9/30)，5%（2/43），(P < 0.01)]，差异有显著性意义，高血压发生率为，显著低于环孢素A组[56%(24/43)，83%，(25/30)，(P < 0.05)]，差异有显著性意义。
结论：他克莫司转换治疗后，肾功能减退得到延缓，蛋白尿减少，血脂代谢得到改善，他克莫司可以有效延缓慢性移植肾肾病进展。
关键词：他克莫司；环孢菌素；肾移植；肾病；移植物

谢续标，彭龙开，彭风华，余少杰，王 彧，姜 奕，蓝恭斌，方春华，聂曼华
中南大学湘雅二医院器官移植中心泌外器官移植科，湖南省长沙市 410011
谢续标☆，男，1970年生，湖南省洞口县人，汉族，1993年湖南医科大学毕业，博士，副教授，主要从事肾移植的基础与临床研究。

中图分类号: R692 文献标识码: A 文章编号: 1673-8225(2008)05-00979-04
谢续标，彭龙开，彭风华，余少杰，王彧，姜奕，蓝恭斌，方春华，聂曼华．他克莫司替换环孢素A对慢性移植肾肾病进展的影响[J].中国组织工程研究与临床康复，2008，12(5):979-982
[www.zglckf.com/zglckf/ejournal/upfiles/08-5/5k-979(ps).pdf]
（Edited by Lavjay B/Yang Y/Wang L）