Evaluation of the Architect® tacrolimus assay in kidney, liver, and heart transplant recipients

The narrow therapeutic range of tacrolimus requires therapeutic drug monitoring to prevent transplant rejection and to minimize nephrotoxicity. The aim of this study was to evaluate the analytical performance of the tacrolimus chemiluminescent microparticle immunoassay (CMIA) in everyday practice comparatively with other methods. CMIA imprecision and accuracy were tested using low, medium, and high concentrations in control samples. The limits of quantification (LOQ) of CMIA and antibody-conjugated magnetic immunoassay (ACMIA) were evaluated using negative whole-blood samples containing 0.4–5.7 ng/ml of tacrolimus from a stock solution. CMIA was compared with ACMIA, enzyme multiplied immunoassay (EMIT), and liquid chromatography–tandem mass spectrometry (LC–MS/MS), using 176 samples from recipients (135 men and 41 women) of heart (n = 19), kidney (n = 107), or liver (n = 50) transplants. CMIA total precision was 5.7%, 3.7% and 3.6% with the low-, medium-, and high-concentration controls, respectively; corresponding values for accuracy were 98%, 104%, and 104%. LOQ was 0.5 (95%CI, 0.22–1.38) with CMIA and 2.5 ng/ml with ACMIA. Linear regression results were as follows: CMIA = 1.2LC–MS/MS + 0.14 (r = 0.98); CMIA = 0.93EMIT + 0.36 (r = 0.975); CMIA = 1.15ACMIA − 0.25 (r = 0.988); and, for tacrolimus concentrations in the 1–15 ng/ml range, of special interest as many transplant recipients are given low-dose tacrolimus, CMIA = 1.05LC–MS/MS + 0.38 (r = 0.94). Two patients had falsely elevated tacrolimus concentrations due to interference in the ACMIA assay; one was a renal transplant recipient who stopped her treatment and had tacrolimus concentrations of 12.5 ng/ml by ACMIA and <0.5 ng/ml by CMIA; the other was an HIV-positive renal transplant recipient whose tacrolimus concentrations by ACMIA were 1.8–43.7-fold those by CMIA. Such interferences with ACMIA, which may be related to endogenous antibodies in the plasma, are likely to negatively impact patient care. In conclusion, the tacrolimus CMIA assay is suitable for routine laboratory use and does not suffer from the interferences seen with ACMIA in some patients.