Diagnostic utility of whole blood cyclosporine measurements in renal transplantation using triple therapy.
Whole blood CsA concentrations measured by specific monoclonal RIA (CYCLO-Trac SP whole blood RIA, IncSTAR) were compared with episodes of renal dysfunction (n = 138) and protocol biopsies (n = 52) that occurred within the first 100 days in consecutive renal allograft recipients receiving triple therapy (n = 92). Histological confirmation of events was available in 98% episodes of acute rejection (n = 60/61), 59% of episodes of CsA nephrotoxicity (22/38), and 100% of the diagnoses of acute tubular necrosis (35/35). Mean, minimum, and maximum CsA levels were elevated in CsA nephrotoxicity compared with all other groups (P < 0.001). Interestingly, CsA levels achieved relative to administered dose also increased at the time of CsA nephrotoxicity compared with other groups (P < 0.01). In the context of acute dysfunction, the sensitivity and specificity of mean CsA levels above 400 ng/ml to predict CsA nephrotoxicity were 32% and 89%, respectively. The negative predictive value of a high CsA level to exclude acute rejection was 88% (at 400 ng/ml), 92% (450 ng/ml), and 95% (500 ng/ml). As a marker of effective immunosuppression, CsA levels were not correlated with in vitro proliferation of PHA-stimulated PBL and did not reduce the severity and degree of cellular infiltration in needle core biopsies during rejection. The sensitivity and specificity of a low CsA level (150 ng/ml) in the diagnosis of acute rejection were 31% and 91%, respectively. The majority of episodes of acute dysfunction, including 63% of CsA nephrotoxicity and 59% of acute rejections, occurred with CsA levels between 150 and 400 ng/ml. In summary, when using low dose triple therapy regimens, CsA levels within the range of 150-400 ng/ml were of little diagnostic value in acute allograft dysfunction. In contrast, levels outside this range were useful in the clinical diagnosis of CsA nephrotoxicity and acute allograft rejection.
Nankivell
B J
BJ
Department of Renal Medicine and Transplantation, Westmead Hospital, Sydney, NSW, Australia.
Hibbins
M
M
Chapman
J R
JR
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D011237:Predictive Value of Tests; D051437:Renal Insufficiency / Q000097:blood / Q000175:diagnosis*
D010835:Phytohemagglutinins; D016572:Cyclosporine