A Differential Impact of Mycophenolic Acid, Prednisolone, and Tacrolimus Exposure on sCD30 Levels in Adult Kidney Transplant Recipients

作者：Barraclough Katherine A^*; Staatz Christine E; Johnson David W; Gillis David; Lee Katie J; McWhinney Brett C; Ungerer Jacobus P J; Campbell Scott B; I**el Nicole M

来源：Therapeutic Drug Monitoring, 2013, 35(2): 240-245.

DOI：10.1097/FTD.0b013e31828286dd

• kidney transplantation
• mycophenolic acid
• prednisolone
• soluble CD30
• tacrolimus

Background: 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.
Aim: To evaluate the influence of mycophenolic acid (MPA), prednisolone, and tacrolimus exposure on sCD30 levels in adult kidney transplant recipients.
Methods: 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.
Results: 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.
Conclusions: 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.

• 出版日期2013-4