Flechner Stuart M, Goldfarb David, Solez Kim, Modlin Charles S, Mastroianni Barbara, Savas Kathy, Babineau Denise, Kurian Sunil, Salomon Daniel, Novick Andrew C, Cook Daniel J
Transplant Center/Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Transplantation. 2007 Apr 15;83(7):883-92. doi: 10.1097/01.tp.0000258586.52777.4c.
We report the 5-year outcomes from a randomized prospective trial in primary adult renal allograft recipients, designed to evaluate calcineurin inhibitor (CNI)-free immunosuppression on kidney transplant function.
Sixty-one patients were randomized to either sirolimus (n=31) or cyclosporine (n=30) after basiliximab induction and mycophenolate mofetil (MMF) with steroids. Sirolimus was concentration controlled at 10-12 ng/mL for at least 6 months.
After 5 years, sirolimus-MMF-steroids compared to cyclosporine-MMF-steroids provides similar patient survival (87.1 vs. 90%, P=0.681), acute rejection rates (12.9 vs. 23.3%, P=0.22), total cholesterol (209.1 vs. 204.3 mg/dL, P=0.973), urine protein/creatinine ratios (0.398 vs. 0.478 mg/dL, P=0.72), and overall medical and surgical morbidity (P=NS). Although unadjusted patient survival was similar, sirolimus based CNI-free patients had longer death censored graft survival (96.4 vs. 76.7%, P=0.0265), higher glomerular filtration rate (GFR) by the abbreviated Modified Diet in Renal Disease (66.7 vs. 50.7 cc/min, P=0.0075), and fewer graft losses from chronic allograft nephropathy. The Banff chronic scores at two years were strong predictors of 5-year GFR. At 5 years, there were six de novo (three solid organ, three skin) cancers in the CNI group and only two de novo (one skin, one leukemia, no solid organ) cancers in the sirolimus group (P=NS).
This study of low to moderate risk patients demonstrates that excellent 5-year kidney transplant outcomes can be achieved without CNI drugs, when therapeutic drug monitoring of sirolimus is employed. The application of CNI drug avoidance protocols to high-risk recipients (retransplants, highly sensitized, etc.), extrarenal allograft recipients, or alternative drug regimens such as steroid or MMF elimination should be subjected to controlled trials.
我们报告了一项针对成年原发性肾移植受者的随机前瞻性试验的5年结果，该试验旨在评估无钙调神经磷酸酶抑制剂（CNI）免疫抑制对肾移植功能的影响。
61例患者在接受巴利昔单抗诱导治疗以及霉酚酸酯（MMF）联合类固醇治疗后，被随机分为西罗莫司组（n = 31）或环孢素组（n = 30）。西罗莫司浓度控制在10 - 12 ng/mL至少6个月。
5年后，与环孢素 - MMF - 类固醇组相比，西罗莫司 - MMF - 类固醇组的患者生存率相似（87.1%对90%，P = 0.681），急性排斥反应率相似（12.9%对23.3%，P = 0.22），总胆固醇水平相似（209.1对204.3 mg/dL，P = 0.973），尿蛋白/肌酐比值相似（0.398对0.478 mg/dL，P = 0.72），总体内科和外科并发症发生率相似（P = 无显著性差异）。尽管未调整的患者生存率相似，但基于西罗莫司的无CNI患者有更长的死亡截尾移植肾生存率（96.4%对76.7%，P = 0.0265），采用简化版肾脏病饮食改良法计算的肾小球滤过率（GFR）更高（66.7对50.7 cc/min，P = 0.0075），且因慢性移植肾肾病导致的移植肾丢失更少。两年时的班夫慢性评分是5年GFR的有力预测指标。5年后，CNI组有6例新发癌症（3例实体器官癌，3例皮肤癌），而西罗莫司组只有2例新发癌症（1例皮肤癌，1例白血病，无实体器官癌）（P = 无显著性差异）。
这项针对低至中度风险患者的研究表明，当采用西罗莫司治疗药物监测时，不使用CNI药物也能取得出色的5年肾移植结果。将避免使用CNI药物方案应用于高风险受者（再次移植、高度致敏等）、肾外移植受者或替代药物方案（如停用类固醇或MMF）应进行对照试验。
