DIAGNOSTIC UTILITY OF WHOLE-BLOOD CYCLOSPORINE MEASUREMENTS IN RENAL-TRANSPLANTATION USING TRIPLE THERAPY

Whole blood CsA concentrations measured by specific monoclonal RIA (CY CLO-Trac SP whole blood RIA, IncSTAR) were compared with episodes of r enal dysfunction (n=138) and protocol biopsies (n=52) that occurred wi thin the first 100 days in consecutive renal allograft recipients rece iving triple therapy (n=92). Histological confirmation of events was a vailable in 98% episodes of acute rejection (n=60/61), 59% of episodes of CsA nephrotoxicity (22/38), and 100% of the diagnoses of acute tub ular necrosis (35/35). Mean, minimum, and maximum CsA levels were elev ated in CsA nephrotoxicity compared with all other groups (P<0.001). I nterestingly, CsA levels achieved relative to administered dose also i ncreased at the time of CsA nephrotoxicity compared with other groups (P<0.01). In the context of acute dysfunction, the sensitivity and spe cificity of mean CsA levels above 400 ng/ml to pre diet CsA nephrotoxi city 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 immunosup pression, CsA levels were not cor related with in vitro proliferation of PHA-stimulated PBL and did not reduce the severity and degree of ce llular infiltration in needle core biopsies during rejection. The sens itivity and specificity of a low CsA level (150 ng/ml) in the diagnosi s of acute rejection were 31% and 91%, respectively. The majority of e pisodes 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 le vels within the range of 150-400 ng/ml were of little diagnostic value in acute allograft dysfunction. In contrast, levels outside this rang e were useful in the clinical diagnosis of CsA nephrotoxicity and acut e allograft rejection.