Falsely Elevated Tacrolimus Concentrations Using Chemiluminescence Microparticle Immunoassay in Kidney Transplant Patient / 대한이식학회지

Tacrolimus is one of the effective immunosuppressive drugs used after an organ transplant procedure. However, due to its narrow therapeutic range, its usefulness in preventing transplant rejection and minimizing nephrotoxicity is dependent on the monitoring of whole blood trough levels of tacrolimus. A 49-year-old kidney transplant recipient presenting with cough and general weakness was admitted to the hospital. Due to the patient's deeply compromised clinical condition, an immunosuppressive therapy was discontinued. Tacrolimus concentrations in the patient's whole blood samples were measured, using an automated chemiluminescent microparticle immunoassay (CMIA) instrument. Interference was suspected because tacrolimus concentrations after the discontinuation of tacrolimus dose were 20.9 and 18.2 ng/mL at day 2 and 3, respectively. Tacrolimus concentrations were 11.1 and 12.6 ng/mL, respectively, when re-tested using an antibody-conjugated magnetic immunoassay (ACMIA). We evaluated the relationship between the CMIA and ACMIA results, and calculated the expected values from the regression equation. Residuals were –8.4 and –4 ng/mL, respectively. There have been several cases with false detection of elevated tacrolimus concentrations using ACMIA; however, such falsely detected elevations using CMIA have rarely been reported. When unexpectedly high concentrations of tacrolimus are detected by CMIA in transplant patients, an immediate re-test using another technique might be necessary to rule out falsely elevated results.

False Increase in Whole Blood Tacrolimus Levels due to Interference in an Antibody-Conjugated Magnetic Immunoassay Method

Tacrolimus is an immunosuppressive agent used to prevent post-transplantation rejection. Tacrolimus has a narrow therapeutic window and therefore, its whole blood concentration is measured for therapeutic drug monitoring. In this report, we present two cases of falsely elevated tacrolimus concentrations identified in recipients of solid organ transplants due to analytical interferences in the antibody-conjugated magnetic immunoassay (ACMIA) method used. Tacrolimus concentrations measured using ACMIA were 4- to 8-fold higher than the values obtained using liquid-chromatography-tandem mass spectrometry (LC-MS/MS) or chemiluminescent micro-particle immunoassay. The cause of this interference remains unknown, but the identification of a possible false elevation of tacrolimus is of paramount importance in clinical practice. Pre-treatment of samples by ethanol extraction or using alternative methods of tacrolimus measurement such as LC-MS/MS are necessary to obtain reliable results in the event of an analytical interference.