Moore Jason, Middleton Lee, Cockwell Paul, Adu Dwomoa, Ball Simon, Little Mark A, Ready Andrew, Wheatley Keith, Borrows Richard
Department of Nephrology and Kidney Transplantation, Renal Institute of Birmingham, University Hospital Birmingham, Edgbaston, Birmingham, United Kingdom.
Transplantation. 2009 Feb 27;87(4):591-605. doi: 10.1097/TP.0b013e318195a421.
Limiting the exposure of kidney transplant recipients to calcineurin inhibitors (CNIs) has potential merit, but there is no clear consensus on the utility of current strategies. In an attempt to aid clarification, we conducted a systematic review and meta-analysis of randomized trials that assessed CNI sparing (minimization or elimination) with mycophenolate as sole adjunctive immunosuppression.
The search strategy identified trials where CNI sparing was accompanied by the continuation of, or conversion to, mycophenolate and compared with standard or higher dose CNI therapy. Two investigators independently examined each trial for eligibility, quality, and outcome measures. Additional subgroup analyses were assessed: (1) de novo CNI sparing; (2) elective CNI sparing beyond 2 months posttransplantation; and (3) CNI sparing for transplant dysfunction.
Nineteen randomized controlled trials met the inclusion criteria permitting analysis of 3312 renal transplant recipients with median follow-up of 12 months. CNI sparing significantly improved glomerular filtration rate (weighted mean difference 4.4 mL/min, 95% confidence interval [CI] 2.9-5.9, P<0.001); with some evidence, albeit weak, of improved graft survival (odds ratio 0.72, 95% CI 0.52-1.01, P=0.06). Acute rejection rates were only increased after elective CNI elimination (odds ratio 2.23, 95% CI 1.57-3.17, P<0.001). There were no significant differences in mortality, malignancy or incidence of infections.
CNI sparing strategies with adjunctive mycophenolate may play an important role in kidney transplant recipients. Improvements in short-term graft function, and possibly graft survival, are achievable. Longer term studies are needed to substantiate the short-term benefits, and refining elective CNI elimination protocols may help to reduce the risk of rejection.
限制肾移植受者接触钙调神经磷酸酶抑制剂（CNIs）具有潜在益处，但对于当前策略的效用尚无明确共识。为了有助于阐明这一问题，我们对评估以霉酚酸作为唯一辅助免疫抑制药物的CNI减量（最小化或消除）的随机试验进行了系统评价和荟萃分析。
检索策略确定了CNI减量同时继续使用或转换为霉酚酸并与标准剂量或更高剂量CNI治疗进行比较的试验。两名研究者独立检查每项试验的纳入资格、质量和结局指标。还进行了额外的亚组分析：（1）初次肾移植时CNI减量；（2）移植后2个月后选择性CNI减量；（3）因移植功能障碍而进行的CNI减量。
19项随机对照试验符合纳入标准，共纳入3312例肾移植受者，中位随访时间为12个月。CNI减量显著改善了肾小球滤过率（加权平均差4.4 mL/分钟，95%置信区间[CI] 2.9 - 5.9，P<0.001）；有一些证据表明移植肾存活率有所提高，尽管证据较弱（比值比0.72，95% CI 0.52 - 1.01，P = 0.06）。仅在选择性消除CNI后急性排斥反应率升高（比值比2.23，95% CI 1.57 - 3.17，P<0.001）。在死亡率、恶性肿瘤或感染发生率方面无显著差异。
联合霉酚酸的CNI减量策略可能在肾移植受者中发挥重要作用。可以实现短期移植肾功能的改善以及可能的移植肾存活率的提高。需要进行长期研究以证实短期益处，完善选择性CNI消除方案可能有助于降低排斥反应风险。
