Cibrik Diane, Meier-Kriesche Herwig-Ulf, Bresnahan Barbara, Wu You Min, Klintmalm Goran, Kew Clifton E, Kuo Paul C, Whelchel John, Cohen David, Baliga Prabakar, Akalin Enver, Benedetti Enrico, Wright Francis, Lieberman Bonnie, Ulbricht Bettina, Jensik Stephen
Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA.
Clin Transplant. 2007 Mar-Apr;21(2):192-201. doi: 10.1111/j.1399-0012.2006.00622.x.
Cyclosporine exposure, as estimated by the area under the curve (AUC), predicts outcomes in renal transplantation. Cyclosporine concentration at two h post-dose (C(2)) has been shown to be the most reliable, single-point surrogate marker for AUC. The objective of this study was to measure renal function beyond month 2 post-transplant using two different C(2) maintenance targets in combination with enteric-coated mycophenolate sodium (EC-MPS), corticosteroids, and basiliximab induction.
In this open-label, multicenter trial, renal transplant recipients entered one of two randomized groups at day 61 post-transplant: group A (higher-C(2) range) or group B (lower-C(2) range).
Patients (164) were recruited, and 141 patients were entered the randomized groups (group A, n = 66; group B, n = 75). At 12 months, the mean calculated creatinine clearance was significantly greater in group B than in group A (79.2 vs. 71.0 mL/min, p < 0.05). Biopsy-proven acute rejection occurred in 14.7% patients in group B and in 24.2% patients in group A (n.s.). During the 12-month trial, 17.7% patients discontinued EC-MPS because of adverse events. Group B (44.0%) had fewer serious adverse events when compared with group A (62.1%; p = 0.04). Overall patient and graft survival were 99.4% and 95.7% respectively. Among 99 high-risk patients (i.e., African-American race, previous transplant, PRA >35% or >4 HLA mismatches), mean creatinine clearance at 12 months was 65.6 mL/min and biopsy-proven rejection occurred in 20.2% patients.
Low cyclosporine C(2) levels are associated with improved renal function compared with higher C(2) levels when used in conjunction with EC-MPS, steroids and basiliximab induction. EC-MPS with low cyclosporine C(2) levels, corticosteroids and basiliximab provides excellent renal function with good efficacy even in high-risk patients.
通过曲线下面积（AUC）估算的环孢素暴露量可预测肾移植的预后。给药后2小时的环孢素浓度（C₂）已被证明是AUC最可靠的单点替代标志物。本研究的目的是在肾移植后第2个月之后，使用两种不同的C₂维持目标，并联合肠溶型霉酚酸钠（EC-MPS）、皮质类固醇和巴利昔单抗诱导治疗，来评估肾功能。
在这项开放标签的多中心试验中，肾移植受者在移植后第61天进入两个随机分组之一：A组（较高C₂范围）或B组（较低C₂范围）。
共招募了164例患者，141例患者进入随机分组（A组，n = 66；B组，n = 75）。在12个月时，B组的平均计算肌酐清除率显著高于A组（79.2对71.0 mL/分钟，p < 0.05）。经活检证实的急性排斥反应在B组患者中的发生率为14.7%，在A组患者中的发生率为24.2%（无统计学差异）。在12个月的试验期间，17.7%的患者因不良事件停用了EC-MPS。与A组（62.1%）相比，B组（44.0%）的严重不良事件较少（p = 0.04）。患者和移植物的总体生存率分别为99.4%和95.7%。在99例高危患者（即非裔美国人、既往移植、群体反应性抗体>35%或>4个HLA错配）中，12个月时的平均肌酐清除率为65.6 mL/分钟，经活检证实的排斥反应发生率为20.2%。
与较高的C₂水平相比，低环孢素C₂水平与肾功能改善相关，当与EC-MPS、类固醇和巴利昔单抗诱导联合使用时。低环孢素C₂水平的EC-MPS、皮质类固醇和巴利昔单抗即使在高危患者中也能提供良好的肾功能和疗效。
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