Cataneo-Dávila A, Zúñiga-Varga J, Correa-Rotter R, Alberú J
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, México.
Transplant Proc. 2009 Dec;41(10):4138-46. doi: 10.1016/j.transproceed.2009.08.065.
Chronic allograft nephropathy (CAN) is a major cause of progressive renal failure in kidney transplant recipients. Its etiology is multifactorial and can be due to immunologic or nonimmunologic conditions including calcineurin inhibitor (CNI) toxicity.
To evaluate the effect of conversion from CNIs to everolimus in kidney transplant recipients with CAN.
In this 12-month pilot study in renal transplant recipients with biopsy-proved CAN, therapy was changed to an everolimus-based immunosuppression regimen. Cyclosporine or tacrolimus dosage was reduced by 80% (group 1, n = 10) or discontinued (group 2, n = 10). Mycophenolate mofetil or azathioprine were withdrawn in group 1, whereas both agents were maintained in group 2. All patients received prednisone.
Twenty renal allograft recipients switched to an everolimus-based regimen, and patients were followed up for a mean (SD) of 12 (0.1) months. Baseline and end-of-study data were as follows: serum creatinine concentration, 1.27 (0.35) mg/dL vs 1.24 (0.4) mg/dL in group 1, and 1.27 mg/dL (0.36) vs 1.25 (0.3) mg/dL in group 2 (difference not significant); and estimated glomerular filtration rate, 72.4 (19.86) mL/min vs 76.26 (22.69) mL/min in group 1 (not significant), and 66.2 (12.95) mL/min vs 66.2 (13.73) mL/min in group 2 (not significant). One patient in group 1 experienced an acute rejection episode (Banff grade Ib), and 2 patients in group 1 and 1 patient in group 2 demonstrated borderline changes, all associated with everolimus blood concentration less than 3 ng/mL.
Reduction or withdrawal of CNI and introduction of everolimus may be useful to slow the rate of loss of renal function in patients with CAN.
慢性移植肾肾病（CAN）是肾移植受者进行性肾衰竭的主要原因。其病因是多因素的，可能归因于免疫或非免疫状况，包括钙调神经磷酸酶抑制剂（CNI）毒性。
评估将CNI转换为依维莫司对CAN肾移植受者的影响。
在这项针对经活检证实为CAN的肾移植受者的12个月试点研究中，治疗改为基于依维莫司的免疫抑制方案。环孢素或他克莫司剂量降低80%（第1组，n = 10）或停用（第2组，n = 10）。第1组停用霉酚酸酯或硫唑嘌呤，而第2组维持使用这两种药物。所有患者均接受泼尼松治疗。
20例肾移植受者转换为基于依维莫司的方案，患者平均（标准差）随访12（0.1）个月。基线和研究结束时的数据如下：血清肌酐浓度，第1组为1.27（0.35）mg/dL，对比1.24（0.4）mg/dL；第2组为1.27 mg/dL（0.36），对比1.25（0.3）mg/dL（差异无统计学意义）；估计肾小球滤过率，第1组为72.4（19.86）mL/min，对比76.26（22.69）mL/min（无统计学意义），第2组为66.2（12.95）mL/min，对比66.2（13.73）mL/min（无统计学意义）。第1组有1例患者发生急性排斥反应（Banff分级Ib级），第1组有2例患者和第2组有1例患者出现临界变化，均与依维莫司血药浓度低于3 ng/mL有关。
减少或停用CNI并引入依维莫司可能有助于减缓CAN患者的肾功能丧失速度。
