title: Clinical correlations of cyclosporine-specific and -nonspecific assays in stable renal transplants, acute rejection, and cyclosporine nephrotoxicity.
abstract: Accurate and early diagnosis of the cause of renal transplant dysfunction is important in successful patient management. Controversy exists as to whether a cyclosporine-specific or -nonspecific method is more predictive of clinical events. In an attempt to answer this question, all episodes of acute renal dysfunction were reviewed in 322 stable renal transplant recipients over a 20-month period. To diagnose the cause of each episode of renal dysfunction, an analysis was made of patient demographics; weight; serum creatinine; cyclosporine dose; cyclosporine level, using a specific method--high-performance liquid chromatography (HPLC)--and a nonspecific method--fluorescent polarization immunoassay (FPIA); changes in cyclosporine dose; renal biopsy; and response to any therapeutic intervention. There were 138 patients, who developed 279 episodes of renal dysfunction. Causes of renal dysfunction were cyclosporine-related (n = 103), acute rejection (n = 63), extracellular fluid volume depletion (n = 27), other (n = 59), and unknown (n = 27). The mean HPLC cyclosporine level was significantly different in patients with acute cyclosporine toxicity (p < 0.001) and patients with acute rejection (p < 0.001) when compared to those with stable renal function; the mean FPIA cyclosporine levels were not significantly different between the three groups. However, a larger percentage of patients with rejection were subtherapeutic when measured by HPLC, while a higher proportion of patients with nephrotoxicity were above the therapeutic range measured by FPIA.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Ohio 45267-0714.
authors.forename: T J
authors.initials: TJ
authors.lastname: Schroeder
authors.forename: N
authors.initials: N
authors.lastname: Sridhar
authors.forename: A J
authors.initials: AJ
authors.lastname: Pesce
authors.forename: J W
authors.initials: JW
authors.lastname: Alexander
authors.forename: M R
authors.initials: MR
authors.lastname: First
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016572:Cyclosporine / Q000009:adverse effects / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016231:Fluorescence Polarization Immunoassay / Q000379:methods; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000139:chemically induced*; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity
chemical_list: D016572:Cyclosporine