Monitoring the tacrolimus concentration in peripheral blood mononuclear cells of kidney transplant recipients

AIMS: Tacrolimus is a critical dose drug and to avoid under‐ and overexposure, therapeutic drug monitoring is standard practice. However, rejection and drug‐related toxicity occur despite whole‐blood tacrolimus pre‐dose concentrations ([Tac](blood)) being on target. Monitoring tacrolimus concentrations at the target site (within peripheral blood mononuclear cells; [Tac](cells)) may better correlate with drug‐efficacy. The aim of this study was to (1) investigate the relationship between [Tac](blood) and [Tac](cells), (2) identify factors affecting the tacrolimus distribution in cells and whole‐blood, and (3) study the relationship between [Tac](cells) and clinical outcomes after kidney transplantation. METHODS: A total of 175 renal transplant recipients were prospectively followed. [Tac](blood) and [Tac](cells) were determined at Months 3, 6 and 12 post‐transplantation. Patients were genotyped for ABCB1 1199G>A and 3435C>T, CYP3A4 15389C>T, and CYP3A5 6986G>A. Data on rejection and tacrolimus‐related nephrotoxicity and post‐transplant diabetes mellitus were collected. RESULTS: Correlations between [Tac](blood) and [Tac](cells) were moderate to poor (Spearman's r = 0.31; r = 0.41; r = 0.61 at Months 3, 6 and 12, respectively). The [Tac](cells)/[Tac](blood) ratio was stable over time in most patients (median intra‐patient variability 39.0%; range 3.5%–173.2%). Age, albumin and haematocrit correlated with the [Tac](cells)/[Tac](blood) ratio. CYP3A5 and CYP3A4 genotype combined affected both dose‐corrected [Tac](blood) and [Tac](cells). ABCB1 was not significantly related to tacrolimus distribution. Neither [Tac](blood) nor [Tac](cells) correlated with clinical outcomes. CONCLUSIONS: The correlation between [Tac](blood) and [Tac](cells) is poor. Age, albumin and haematocrit correlate with the [Tac](cells)/[Tac](blood) ratio, whereas genetic variation in ABCB1, CYP3A4 and CYP3A5 do not. Neither [Tac](blood) nor [Tac](cells) correlated with clinical outcomes.