3 years ago

A comparison of the effects of CYP3A5 polymorphism on tacrolimus blood concentrations measured by 4 immunoassay methods in renal transplant patients

A comparison of the effects of CYP3A5 polymorphism on tacrolimus blood concentrations measured by 4 immunoassay methods in renal transplant patients
Yumiko Akamine, Tadashi Ohkubo, Shigeru Satoh, Hideaki Kagaya, Masatomo Miura
What is known and objective The anti-tacrolimus antibodies used in commercial immunoassay methods have cross-reactivity with tacrolimus metabolites. The aim of this study was to investigate differences in the effects of CYP3A5 polymorphism on tacrolimus concentrations obtained by four immunoassay methods in renal transplant patients. Methods Samples (n = 508) were evaluated using four immunoassays (chemiluminescence enzyme immunoassay [CLIA], affinity column-mediated immunoassay [ACMIA], electrochemiluminescence immunoassay [ECLIA] and latex agglutination turbidimetric immunoassay [LTIA]). Results Bland-Altman plots showed average biases of −0.12 (±1.96 SD: −1.30-1.05) ng/mL for CLIA, −0.30 (−1.59-1.00) ng/mL for ECLIA, 0.42 (−1.21-2.05) ng/mL for ACMIA and 1.88 (−0.51-4.28) ng/mL for LTIA, when considering the mean of the three immunoassays (CLIA, ECLIA and ACMIA). In multiple regression analysis, the difference (CLIA—mean) was affected by haematocrit levels. Differences in ECLIA were correlated with red blood cell counts. For LTIA, CYP3A5 genotype and haematocrit levels were identified as independent predictors for this bias. What is new and conclusion The results obtained by CLIA, ECLIA and ACMIA were not affected by CYP3A5 polymorphism. However, in LTIA, CYP3A5*1/*3-derived data exhibited an inverse relationship in Bland-Altman analysis (slope: −0.0824). Higher cross-reactivity with 12-hydroxy tacrolimus at lower concentrations may occur in patients with the CYP3A5*1/*3 genotype. Because patients with the CYP3A5*1 allele identified using LTIA may show higher blood concentrations of tacrolimus at lower target concentrations, for example 3.0 ng/mL, compared with other immunoassay methods, there is a need for sufficient consideration of the interpretation of values measured by LTIA. The results obtained by LTIA was affected by CYP3A5 polymorphism, but not CLIA, ECLIA and ACMIA. Because patients with the CYP3A5*1 allele, as determined using LTIA, may exhibit higher blood concentrations of tacrolimus at a lower target concentration, for example, 3.0 ng/mL, compared with other immunoassay methods, there is a need for sufficient consideration of the interpretation of values measured by LTIA.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/jcpt.12624

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