Kidney transplantation without calcineurin inhibitor drugs: A prospective, randomized trial of sirolimus versus cyclosporin
Kidney transplantation without calcineurin inhibitor drugs: A prospective, randomized trial of sirolimus versus cyclosporin
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DOI：
10.1097/00007890-200210270-00002
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发表时间：
2002-10-27
期刊：
影响因子：
6.2
通讯作者：
Novick, AC
中科院分区：
文献类型：
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作者：
Flechner, SM;Goldfarb, D;Novick, AC
背景钙调神经磷酸酶抑制剂药物引起的进行性肾毒性是肾移植患者肾功能长期下降的原因。我们在61例成人初次肾移植受者中进行了一项钙调磷酸酶抑制剂药物回避的随机前瞻性试验。每例患者在第0天和第4天接受巴利昔单抗20 mg诱导治疗，并接受吗替麦考酚酯1 g每日2次和类固醇的维持治疗。31例患者在15 mg负荷剂量后接受西罗莫司5 mg/d。然后对剂量进行浓度控制，使24小时谷浓度保持在10 - 12 ng/mL，持续6个月，此后保持在5 - 10 ng/mL。30例患者开始环孢霉素治疗，剂量为6 ~ 8 mg/kg/d，分次给药，然后控制浓度，使12小时谷值保持在200 ~ 250 ng/mL。平均随访18.1个月（范围：12-26个月）。西罗莫司治疗组患者的1年生存率、移植物存活率和活检证实的急性排斥反应发生率（分别为96.7%、96.7%和6.4%）与环孢素治疗组患者（分别为100%、95.4%和16.6%）无显著差异。在6个月和12个月时，西罗莫司治疗的患者分别享有明显更好的（P=0.008和P=0.004）平均血清肌酐水平（1.29和1.32 mg/dL）和计算的肌酐清除率（77.8和81.1 mL/min）比环孢素治疗患者（分别为1.74和1.78 mg/dL，64.1和61.1 mL/min）。西罗莫司治疗的受试者1年霉酚酸谷浓度（4.16 ng/mL）显著（P=0.001）高于环孢素治疗的患者（1.93 ng/mL）。与环孢霉素相比，西罗莫司还能延迟巴利昔单抗耗竭的CD 25（+）T细胞的再增殖。钙调磷酸酶抑制剂药物避免与巴利昔单抗诱导和西罗莫司提供了相当的1年移植结果，与显着更好的肾功能在原发性肾移植受者。
Background. Progressive nephrotoxicity caused by calcineurin inhibitor drugs contributes to the long-term decline in renal function in kidney transplant patients.Methods. We conducted a randomized, prospective trial of calcineurin inhibitor drug avoidance in 61 adult primary kidney transplant recipients. Each patient received induction therapy with 20 mg basiliximab on days 0 and 4, and maintenance therapy with mycophenolate mofetil 1 g two times per day and steroids. Thirty-one patients received sirolimus, 5 mg daily after a 15-mg loading dose. Doses were then concentration-controlled to keep 24-hr trough levels at 10 to 12 ng/mL for 6 months and 5 to 10 ng/mL thereafter. Thirty patients began cyclosporine therapy at 6 to 8 mg/kg per day in divided doses and were then concentration-controlled to keep 12-hr troughs of 200 to 250 ng/mL.Results. Mean follow-up is 18.1 months (range, 12-26 months). The percentages of 1-year patient survival, graft survival, and biopsy-confirmed acute rejection rates were not significantly different between the sirolimus-treated patients (96.7%, 96.7%, and 6.4%, respectively) and the cyclosporine-treated patients (100%, 95.4%, and 16.6%, respectively). At 6 and 12 months, respectively, the sirolimus-treated patients enjoyed significantly better (P=0.008 and P=0.004) mean serum creatinine levels (1.29 and 1.32 mg/dL) and calculated creatinine clearances (77.8 and 81.1 mL/min) than cyclosporine-treated patients (1.74 and 1.78 mg/dL, and 64.1 and 61.1 mL/min, respectively). Sirolimus-treated recipients have significantly (P=0.001) higher 1-year trough levels of mycophenolic acid (4.16 ng/mL) than cyclosporine-treated patients (1.93 ng/mL). Sirolimus also delays the repopulation of basiliximab-depleted CD25(+) T cells compared with cyclosporine.Conclusions. Calcineurin inhibitor drug avoidance with basiliximab induction and sirolimus provides comparable 1-year transplant outcomes, with significantly better renal function in primary renal allograft recipients.