Therapeutic drug monitoring of tacrolimus in kidney transplantation

Calcineurin inhibitors (CNI) are the backbone of present-day immunosuppressive regimen in kidney transplant recipients. Tacrolimus (TAC) has gradually replaced cyclosporine as CNI of choice due to its better potency and side effect profile. One of the key challenges in using TAC is therapeutic drug monitoring (TDM) of TAC, as it is a drug of narrow therapeutic index. Various methods of TDM are available; there are older immunoassay (IA)-based methods and recent liquid chromatogram (LC) based. The problems with older IAs like microparticle enzyme IA (Abbott Diagnostics, Chicago, IL, USA), and enzyme multiplied IA (EMIT, Dade Behring, Glasgow, DE, USA) are; they are not so accurate, there is interference with other substances, they measure inactive metabolite, and their limit of detection is not wide. The LC-based methods such as liquid chromatogram mass spectroscopy or LC-tandem mass spectroscopy overcome these issues; however, they are costly, labor intensive, and require good technical support. Newer IAs, such as chemiluminescent microparticle IA (Abbott Diagnostics) and Quantitative Microsphere System (QMS (TM), Thermo-Fisher), have functional sensitivity <1 ng/ml, and overcome the disadvantages of older IAs. These newer IA are reported to offer adequate accuracy and precision, and at the same time, they are easy to perform. There is genetic variation in expression of cytochrome p-450 (CYP3A4) and CYP3A5 enzymes, which metabolizes TAC, resulting in different levels with same doses. Patients who are expressers (CYP3A5 1*/1* OR CYP3A5 1*/3*) require higher doses to maintain the same levels compared to nonexpressers (CYP3A5 3*/3*).