Clinical correlations of cyclosporine-specific and -nonspecific assays in stable renal transplants, acute rejection, and cyclosporine nephrotoxicity.
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)
Schroeder
T J
TJ
Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Ohio 45267-0714.
Sridhar
N
N
Pesce
A J
AJ
Alexander
J W
JW
First
M R
MR
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
D016572:Cyclosporine