Department of Surgery, Klinikum Rechts der Isar, TU Munich, Ismaningerstr. 22, 81675, Munich, Germany.
Dig Dis Sci. 2011 Jan;56(1):244-51. doi: 10.1007/s10620-010-1386-z. Epub 2010 Sep 8.
The aim of this trial was to evaluate the impact of conversion from a calcineurin-inhibitor (CNI)-based immunosuppressive regimen to mycophenolate mofetil (MMF) and reduced-dose CNI on long-term renal function and survival in a series of 63 liver transplant patients with CNI-induced renal dysfunction.
CNI dosage was significantly tapered after introduction of 2,000 mg MMF per day. Renal function was assessed by determination of serum creatinine levels and calculated creatinine clearance (CCl). The impact of relevant clinical parameters on renal function and survival post-conversion was analyzed by univariate and multivariate analysis.
At 60 months post-conversion, mean creatinine level had significantly declined from 197.2±58.3 μmol/l at baseline to 160.0±76.5 μmol/l, and mean CCl has significantly increased from 38.4±13.4 ml/min at baseline to 47.9±21.1 ml/min (p<0.001), respectively. Forty-six patients (73.1%) demonstrated sustained renal response to modified immunosuppression. Full-dose MMF medication (p=0.006) and the early conversion (p=0.02) were identified as independent predictors of persistent renal function improvement. Sustained renal response to MMF plus reduced-dose CNI was identified as the most relevant independent promoter of long-term survival (hazard ratio 6.9). Five-year survival rate post-conversion was 93.9% in renal responders and 64.3% in renal non-responders (log rank<0.001).
Sustained renal response to MMF and CNI dose reduction promotes long-term survival in liver transplant patients with CNI-induced renal dysfunction.
本试验旨在评估将钙调磷酸酶抑制剂(CNI)为基础的免疫抑制方案转换为吗替麦考酚酯(MMF)和减少剂量 CNI 对 63 例 CNI 诱导肾功能障碍的肝移植患者的长期肾功能和生存的影响。
在引入 2000mg MMF 每天后,显著减少 CNI 的剂量。通过测定血清肌酐水平和计算肌酐清除率(CCl)评估肾功能。通过单因素和多因素分析,分析相关临床参数对转换后肾功能和生存的影响。
转换后 60 个月时,平均肌酐水平从基线时的 197.2±58.3μmol/L 显著下降至 160.0±76.5μmol/L,平均 CCl 从基线时的 38.4±13.4ml/min 显著增加至 47.9±21.1ml/min(p<0.001)。46 例(73.1%)对改良免疫抑制有持续的肾脏反应。全剂量 MMF 治疗(p=0.006)和早期转换(p=0.02)被确定为持续肾功能改善的独立预测因子。MMF 联合减少剂量 CNI 的持续肾脏反应被确定为长期生存的最相关独立促进因素(危险比 6.9)。转换后 5 年的生存率在肾反应者中为 93.9%,在肾无反应者中为 64.3%(对数秩<0.001)。
MMF 和 CNI 剂量减少的持续肾脏反应促进了 CNI 诱导肾功能障碍的肝移植患者的长期生存。