The value of C2 monitoring in stable renal allograft recipients on maintenance immunosuppression

被引:43
作者
Einecke, G
Mai, I
Fritsche, L
Slowinski, T
Waiser, J
Neumayer, HH
Budde, K
机构
[1] Humboldt Univ, Charite, Dept Nephrol, D-10117 Berlin, Germany
[2] Humboldt Univ, Charite, Dept Clin Pharmacol, D-10117 Berlin, Germany
关键词
C-2; monitoring; cyclosporin A; maintenance immunosuppression; pharmacokinetics; renal transplant;
D O I
10.1093/ndt/gfg434
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
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.
引用
收藏
页码:215 / 222
页数:8
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