title: Serum cyclosporine kinetic profile. Failure to correlate with nephrotoxicity or rejection episodes following sequential immunotherapy for renal transplantation.
abstract: Cyclosporine (CsA) level monitoring in renal transplant recipients has been thought to aid in separating clinical episodes of nephrotoxicity from rejection. Twenty-four-hour CsA pharmacodynamic profiles were obtained from 85 consecutive primary renal transplant recipients in the immediate peritransplant period in order to determine the value of this test in predicting subsequent episodes of nephrotoxicity or rejection. All patients were treated with sequential antilymphoblast globulin/CsA following transplantation. Serum samples from each recipient were analyzed for CsA levels estimated by radioimmunoassay (RIA) four days after initiation of a daily single oral CsA dose (10 mg/kg/day). A total of 52 episodes of rejection and 303 episodes of nephrotoxicity occurring within the first six months posttransplant were correlated with selected parameters from the immediate posttransplant CsA kinetic profile. For each profile these parameters were maximum CsA level, time to maximum CsA level, minimum CsA level, 95% clearance time of CsA, and total CsA accumulation and clearance during the 24 hr following ingestion of CsA. No significant correlation was found between any of these parameters and either the incidence or frequency of rejection or nephrotoxic episodes, as determined by least-squares linear regression analysis. Furthermore, following a single oral dose of CsA (10 mg/kg/day), no correlation could be found between the dose and the absorption, accumulation, metabolism, and clearance of the drug. In conclusion, maximum CsA level, time to maximum CsA level, minimum CsA level, 95% clearance time of CsA, and total CsA accumulation and clearance measured from CsA kinetic profiles cannot be correlated with or predict the incidence of rejection or nephrotoxic episodes that subsequently occur during the first six months following renal transplantation.
authors.affiliation: Department of Surgery, Ohio State University College of Medicine, Columbus 43210.
authors.forename: B G
authors.initials: BG
authors.lastname: Sommer
authors.forename: D E
authors.initials: DE
authors.lastname: Sing
authors.forename: M L
authors.initials: ML
authors.lastname: Henry
authors.forename: R M
authors.initials: RM
authors.lastname: Ferguson
authors.forename: C G
authors.initials: CG
authors.lastname: Orosz
mesh_terms: D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D001379:Azathioprine / Q000008:administration & dosage; D003524:Cyclosporins / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage
chemical_list: D000961:Antilymphocyte Serum; D003524:Cyclosporins; D001379:Azathioprine; D011241:Prednisone