Department of Nephrology, University of Queensland at Princess Alexandra Hospital, Brisbane, Australia.
Ther Drug Monit. 2013 Apr;35(2):240-5. doi: 10.1097/FTD.0b013e31828286dd.
Soluble CD30 (sCD30) has been associated with rejection and graft loss in kidney transplantation, leading to the suggestion that sCD30 might be a useful biomarker to adjust immunosuppressant medication dosing. However, there has been minimal study of the influence of individual immunosuppressive drugs on sCD30 levels.
To evaluate the influence of mycophenolic acid (MPA), prednisolone, and tacrolimus exposure on sCD30 levels in adult kidney transplant recipients.
The sCD30 levels were measured pretransplant and 30 days posttransplant. Area under the concentration-time curve (AUC) for each drug was estimated on day 30 using validated, multiple regression-derived limited sampling strategies.
One hundred twenty-five subjects were included. Median (interquartile range) sCD30 levels were lower on day 30 posttransplant compared with pretransplant [10.7 (3.7-20.1) pg/mL versus 66.5 (46.0-95.1) pg/mL; P < 0.0001]. On univariate analyses, day 30 sCD30 levels were negatively correlated with MPA exposure and positively correlated with tacrolimus exposure. Using multivariate logistic regression, higher tacrolimus exposure was independently associated with higher day 30 sCD30 levels (2.2 change in odds for an SD increase in tacrolimus AUC 0-12, P = 0.01; 5.5 change in odds for an SD increase in tacrolimus predose concentration, P < 0.0001). In contrast, MPA and total and free prednisolone exposures were not independently associated with sCD30 levels.
The sCD30 levels are significantly reduced in the presence of combination immunosuppression but are differentially affected by different immunosuppressant agents. More research is required before introduction of sCD30 measurement into clinical practice can be considered.
可溶性 CD30（sCD30）与肾移植中的排斥反应和移植物丢失有关，这导致人们认为 sCD30 可能是调整免疫抑制剂药物剂量的有用生物标志物。然而，关于个体免疫抑制剂药物对 sCD30 水平的影响的研究很少。
评估吗替麦考酚酸（MPA）、泼尼松龙和他克莫司暴露对成年肾移植受者 sCD30 水平的影响。
在移植前和移植后 30 天测量 sCD30 水平。使用验证的、基于多变量回归的有限采样策略在第 30 天估算每种药物的浓度-时间曲线下面积（AUC）。
共纳入 125 例受试者。与移植前相比，移植后 30 天 sCD30 水平中位数（四分位距）较低[10.7（3.7-20.1）pg/mL 比 66.5（46.0-95.1）pg/mL；P<0.0001]。在单变量分析中，第 30 天 sCD30 水平与 MPA 暴露呈负相关，与他克莫司暴露呈正相关。使用多变量逻辑回归，较高的他克莫司暴露与第 30 天 sCD30 水平升高独立相关（他克莫司 AUC0-12 的一个标准差增加，优势比增加 2.2[P=0.01]；他克莫司预剂量浓度的一个标准差增加，优势比增加 5.5[P<0.0001]）。相反，MPA 和总泼尼松龙及游离泼尼松龙暴露与 sCD30 水平无独立相关性。
在联合免疫抑制存在的情况下，sCD30 水平显著降低，但不同免疫抑制剂药物的影响不同。在考虑将 sCD30 测量引入临床实践之前，还需要进行更多的研究。
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