Schlitt H J, Barkmann A, Böker K H, Schmidt H H, Emmanouilidis N, Rosenau J, Bahr M J, Tusch G, Manns M P, Nashan B, Klempnauer J
Klinik für Viszeral und Transplantationschirurgie, Medizinische Hochschule Hannover, Germany.
Lancet. 2001 Feb 24;357(9256):587-91. doi: 10.1016/s0140-6736(00)04055-1.
Renal dysfunction is a major complication of long-term immunosuppressive therapy with calcineurin inhibitors (CNI) in liver-transplant recipients. We undertook a randomised study to assess the safety and efficacy of CNI withdrawal and replacement by mycophenolate mofetil.
28 people who had had renal dysfunction attributable to suspected CNI toxicity after liver transplantation participated in the study. We replaced CNI with mycophenolate mofetil in a stepwise pattern in half the group (study patients); the other half (controls) stayed on CNI immunosuppression. Renal function, blood pressure, uric acid, and blood lipids were measured before and 6 months after study entry. Side-effects of medication and graft function were recorded throughout the study.
At the end of the study, mean (SD) serum creatinine had fallen by 44.4 (48.7) micromol/L in study patients compared with 3.1 (14.3) micromol/L in controls; a mean difference of 41.3 micromol/L (95% CI 12.4-70.2). Moreover, systolic and diastolic blood pressure, and serum uric acid decreased significantly in the study group but not in the control group (mean [95% CI] between group differences 10.8 mm Hg [3.0-18.6], 5.0 mm Hg [0.9-9.2], and 83.1 micromol/L [12.7-153.6], respectively). There were no changes in cholesterol or triglyceride concentrations in either group. Side-effects were reported by eight of the study patients. Three reversible episodes of acute graft rejection occurred in study patients during mycophenolate mofetil monotherapy, whereas none occurred in the control group.
Substitution of CNI by mycophenolate mofetil can improve renal function, blood pressure, and uric acid concentration of liver-transplant patients, but there is an increased rejection risk with mycophenolate mofetil monotherapy.
肾功能不全是肝移植受者长期使用钙调神经磷酸酶抑制剂（CNI）进行免疫抑制治疗的主要并发症。我们进行了一项随机研究，以评估停用CNI并用霉酚酸酯替代的安全性和有效性。
28例肝移植后因疑似CNI毒性导致肾功能不全的患者参与了该研究。我们将研究组（一半患者）的CNI逐步替换为霉酚酸酯；另一半（对照组）继续接受CNI免疫抑制治疗。在研究开始前和开始后6个月测量肾功能、血压、尿酸和血脂。在整个研究过程中记录药物副作用和移植物功能。
研究结束时，研究组患者的平均（标准差）血清肌酐下降了44.4（48.7）μmol/L，而对照组下降了3.1（14.3）μmol/L；平均差异为41.3μmol/L（95%CI 12.4 - 70.2）。此外，研究组的收缩压和舒张压以及血清尿酸显著下降，而对照组未下降（组间平均差异[95%CI]分别为10.8 mmHg[3.0 - 18.6]、5.0 mmHg[0.9 - 9.2]和83.1 μmol/L[12.7 - 153.6]）。两组的胆固醇或甘油三酯浓度均无变化。8例研究组患者报告了副作用。在霉酚酸酯单药治疗期间，研究组患者发生了3次可逆性急性移植物排斥反应，而对照组未发生。
用霉酚酸酯替代CNI可改善肝移植患者的肾功能、血压和尿酸浓度，但霉酚酸酯单药治疗会增加排斥反应风险。
