title: Blood cyclosporin concentrations but not doses correlate with acute changes in renal function following heart and heart-lung transplantation.
abstract: The relationship between changes in cyclosporin (CyA) dose or CyA blood concentration and the reciprocal creatinine concentration was investigated by cross-correlation analysis over the first 3 postoperative months in 32 consecutive heart and heart-lung recipients. Exploratory analysis suggested that early changes in renal function, probably attributable to recovery from preoperative cardiac failure, obscured later underlying correlations. Therefore, all data up to the first nadir in plasma creatinine following transplantation were excluded from the analysis. Five-day mean CyA doses or blood concentrations were cross-correlated with 5-day mean reciprocal creatinine concentrations measured either in the same 5-day period or with the creatinine measured up to two 5-day periods later. Although a significant correlation was found between CyA dose and blood concentration (the 95% confidence interval of the population correlation coefficient did not overlap zero), there was no relationship between dose and changes in renal function. The blood CyA concentration, however, correlated significantly with the reciprocal creatinine concentration measured in the same 5-day period and was also predictive of changes in creatinine measured in the subsequent 5-day period. Thus, a major criterion for therapeutic drug monitoring had been fulfilled: CyA dosage adjustment based on blood CyA concentrations, as the intermediate therapeutic end point, is helpful in the management of acute nephrotoxicity in heart and heart-lung transplant recipients because of the lack of a dose-effect relationship. Regular CyA monitoring and appropriate dosage adjustment is essential for the management of acute nephrotoxicity in the first 3 months following heart or heart-lung transplantation.
authors.affiliation: Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, England.
authors.forename: A K
authors.initials: AK
authors.lastname: Trull
authors.forename: N G
authors.initials: NG
authors.lastname: Best
authors.forename: K K
authors.initials: KK
authors.lastname: Tan
authors.forename: K L
authors.initials: KL
authors.lastname: Hue
authors.forename: T W
authors.initials: TW
authors.lastname: Higenbottam
authors.forename: S
authors.initials: S
authors.lastname: Large
authors.forename: J
authors.initials: J
authors.lastname: Wallwork
mesh_terms: D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D016027:Heart Transplantation / Q000502:physiology*; D016041:Heart-Lung Transplantation / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000502:physiology*
chemical_list: D016572:Cyclosporine; D003404:Creatinine