Lai Wei, Lu Shi-Chun, Wang Meng-Long, Zhang Jing, Wu Ju-Shan, Dai Jun, Zeng Dao-Bing, Xia Ren-Pin, Li Ning
Department of Hepatobiliary Surgery & Liver Transplantation Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
Zhonghua Yi Xue Za Zhi. 2009 Jun 9;89(22):1529-32.
Renal dysfunction caused by calcineurin inhibitor (CNI) after liver transplantation is a major complication among the long-term surviving recipients. Several studies have demonstrated that the adverse events could be prevented or avoided by mycophenolate mofetil (MMF)-based CNI reduced immunosuppressive protocol. In this retrospective study, we analyzed the middle-term effect of this regimen upon improving the CNI-associated renal dysfunction.
124 OLT recipients' data within the recent three years were reviewed in this study.
Renal dysfunction developed in 14 cases and its incidence was 11.29%. Five cases of them were from cyclosporine A (CsA) group and 9 from tacrolimus (TAC) group. The postoperative time ranged from 3-39 months with a mean follow-up duration of 19.26 +/- 9.30 months. The interval between renal impairment and surgery was 12.92 +/- 9.04 (1-31) months. CNI were reduced stepwise by about 55% in TAC group (TAC 2.60 +/- 1.14 mg/d vs 1.10 +/- 0.22 mg/d; t = 3.000, P = 0.040) and about 70% in CsA group (CsA 370 +/- 179 mg/d vs 105 +/- 27; t = 3.359, P = 0.028). Serum creatinine had decreased from 139 +/- 46 micromol/L to 122 +/- 46 micromol/L (t = 3.152, P = 0.004), 114 +/- 53 micromol/L (t = 4.180, P = 0.001) and 93 +/- 18 micromol/L (t = 4.721, P = 0.000) after administrating a mean MMF dose of 1.05 +/-0.15 g/d (0.5-1.5 g/d) for 1, 2 and 3 months respectively. And the creatinine clearance rate increased from 51.83 +/- 21.28 ml/min to 63 +/- 22 ml/min (t = -3.439, P = 0.004), 69 +/- 25 ml/min (t = -4.207, P = 0.001) and 79 +/- 25 m/min (t = -6.149, P = 0.000) during the corresponding period. Improvement was maintained within a follow-up period of 6.00 +/- 3.37 (3-14) months without major immunological or non-immunological side effects, except for 1 recipient from another institution who died of CNI-associated renal failure within 1 month after burst. 71.43% (10/14) of recipients achieved the normalization of serum creatinine and 21.43% (3/14) experienced a significant reduction in their serum creatinine levels. Conclusions MMF-based CNI reduced immunosuppressive protocol can improve substantially CNI-associated renal dysfunction after liver transplantation. And the long-term surviving recipients have excellent profiles of safety and tolerance.
肝移植后由钙调神经磷酸酶抑制剂（CNI）引起的肾功能障碍是长期存活受者中的主要并发症。多项研究表明，基于霉酚酸酯（MMF）的减少CNI的免疫抑制方案可预防或避免不良事件。在这项回顾性研究中，我们分析了该方案对改善CNI相关肾功能障碍的中期效果。
本研究回顾了最近三年来124例肝移植受者的数据。
14例出现肾功能障碍，发生率为11.29%。其中5例来自环孢素A（CsA）组，9例来自他克莫司（TAC）组。术后时间为3 - 39个月，平均随访时间为19.26±9.30个月。肾功能损害与手术的间隔时间为12.92±9.04（1 - 31）个月。TAC组CNI逐步减少约55%（TAC 2.60±1.14mg/d对1.10±0.22mg/d；t = 3.000，P = 0.040），CsA组减少约70%（CsA 370±179mg/d对105±27；t = 3.359，P = 0.028）。分别给予平均剂量为1.05±0.15g/d（0.5 - 1.5g/d）MMF 1、2和3个月后，血清肌酐从139±46μmol/L分别降至122±46μmol/L（t = 3.152，P = 0.004）、114±53μmol/L（t = 4.180，P = 0.001）和93±18μmol/L（t = 4.721，P = 0.000）。相应时期内肌酐清除率从51.83±21.28ml/min升至63±22ml/min（t = -3.439，P = 0.004）、69±25ml/min（t = -4.207，P = 0.001）和79±25ml/min（t = -6.149，P = 0.000）。在6.00±3.37（3 - 14）个月的随访期内改善情况得以维持，无重大免疫或非免疫副作用，除了1例来自其他机构的受者在突发后1个月内死于CNI相关肾衰竭。71.43%（10/14）的受者血清肌酐恢复正常，21.43%（3/14）的受者血清肌酐水平显著降低。结论基于MMF的减少CNI免疫抑制方案可显著改善肝移植后CNI相关肾功能障碍。长期存活受者具有良好的安全性和耐受性。
