The value of C2 monitoring in stable renal allograft recipients on maintenance immunosuppression
The value of C2 monitoring in stable renal allograft recipients on maintenance immunosuppression
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DOI：
10.1093/ndt/gfg434
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发表时间：
2004-01-01
影响因子：
6.1
通讯作者：
Budde, K
中科院分区：
文献类型：
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作者：
Einecke, G;Mai, I;Budde, K
背景。环孢素 A (CyA) 是一种治疗窗窄且药代动力学高度可变的药物。治疗药物监测至关重要，并且通常以谷值 (C-0) 为指导。最近的证据表明，CyA 给药后 2 小时（C-2）进行单次血液浓度测量比 C-0 测定更能准确预测药物暴露和临床事件。迄今为止，关于肾移植受者 C-2 监测的风险和益处的前瞻性数据有限，并且在维持患者中进行 C-2 监测的经验很少。方法。在 127 名长期同种异体肾移植受者中，除了常规 C-0 之外，我们还测定了 C-2 水平，并观察了 13.6 +/- 3.1 个月的临床结果。为了确定监测的精度，我们在 46 名没有改变剂量的稳定患者中重复测定了 C-0 和 C-2 水平。结果。临床结果非常出色（患者存活率 100%，移植物存活率 97%），仅出现两次边缘排斥反应，尽管 C-2 水平 (564 +/- 186 ng/ml) 低于迄今为止维持治疗患者的推荐水平。我们发现排斥反应和 CyA 毒性患者之间的 C-2 水平没有显着差异。受试者操作特征 (ROC) 分析显示，C-2 水平无法预测排斥、毒性或感染的风险。对 46 名患者的 C-0 和 C-2 水平的重复测定显示患者内部存在较高的变异性。在这些患者中，C-2 的变异系数仅比 C-0 稍好一些。结论。我们的结论是，在维持治疗的患者中，500 至 600 ng/ml 之间的 C-2 浓度具有良好的耐受性，并可提供有效且安全的排斥反应预防。尽管平均 C-2 水平似乎无助于识别有排斥风险的患者，但它们可能有助于检测过度免疫抑制并通过降低 CyA 肾毒性进一步提高同种异体移植物的长期存活率。
Background. Cyclosporin A (CyA) is a drug with a narrow therapeutic window and highly variable pharmacokinetics. Therapeutic drug monitoring is essential and conventionally has been guided by trough levels (C-0). Recent evidence indicates that a single blood concentration measurement 2 h after CyA administration (C-2) is a more accurate predictor of drug exposure and clinical events than determination of C-0. To date, limited prospective data are available with respect to risks and benefits of C-2 monitoring in renal transplant recipients, and little experience exists with C-2 monitoring in maintenance patients.Methods. In 127 long-term renal allograft recipients, we determined C-2 levels in addition to conventional C-0 and observed clinical outcome over a period of 13.6 +/- 3.1 months. To determine the precision of monitoring, we repeatedly determined C-0 and C-2 levels in 46 stable patients without dose change.Results. Clinical outcome was excellent (patient survival 100%, graft survival 97%), with only two borderline rejections, although C-2 levels (564 +/- 186 ng/ml) were lower than recommended so far for maintenance patients. We found no significant differences in C-2 levels between patients with rejection and CyA toxicity. Receiver operating characteristic (ROC) analysis showed no prediction for risk of rejection, toxicity or infection by C-2 levels. Repeated determinations of both C-0 and C-2 levels in 46 patients revealed a high intra-patient variability. In these patients, the coefficient of variation for C-2 was only marginally better compared with C-0.Conclusions. We conclude that in maintenance patients, C-2 concentrations between 500 and 600 ng/ml are well tolerated and provide effective and safe rejection prophylaxis. Although mean C-2 levels do not seem to be helpful in identifying patients at risk for rejection, they may be useful to detect over-immunosuppression and to improve long-term allograft survival further by reducing CyA nephrotoxicity.