title: A differential impact of mycophenolic acid, prednisolone, and tacrolimus exposure on sCD30 levels in adult kidney transplant recipients.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Nephrology, University of Queensland at Princess Alexandra Hospital, Brisbane, Australia. arbieb@hotmail.com
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Barraclough
authors.forename: Christine E
authors.initials: CE
authors.lastname: Staatz
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
authors.forename: David
authors.initials: D
authors.lastname: Gillis
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Lee
authors.forename: Brett C
authors.initials: BC
authors.lastname: McWhinney
authors.forename: Jacobus P J
authors.initials: JP
authors.lastname: Ungerer
authors.forename: Scott B
authors.initials: SB
authors.lastname: Campbell
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Isbel
mesh_terms: D000328:Adult; D053285:CD30 Ligand / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000627:therapeutic use*; D011239:Prednisolone / Q000627:therapeutic use*; D011446:Prospective Studies; D012995:Solubility; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D053285:CD30 Ligand; D007166:Immunosuppressive Agents; C505774:TNFSF8 protein, human; D011239:Prednisolone; D009173:Mycophenolic Acid; D016559:Tacrolimus