The tacrolimus concentration‐to‐dose ratio is associated with kidney function in heart transplant recipients

Aim Heart transplantation (HT) is frequently complicated by chronic kidney disease, of which tacrolimus‐related nephrotoxicity is an important cause. In kidney and liver transplant recipients, fast tacrolimus metabolism (defined as a low concentration‐to‐dose [ C 0 / D ] ratio), negatively affects kidney function. Here, the association between the C 0 / D ratio and kidney function in HT recipients was investigated. Methods This was a retrospective study including 209 HT recipients who received an immediate‐release tacrolimus formulation. The C 0 / D ratio and kidney function (estimated glomerular filtration rate [eGFR]) were assessed at 3, 6, 12, 36 and 60 months post‐HT. Patients were categorized as fast, intermediate and slow metabolisers, depending on their individual median C 0 / D ratio as calculated over the follow‐up period. A linear mixed‐effects model analysis was performed, in which the time‐varying eGFR was the dependent variable. Results The distribution of the individual median C 0 / D ratios ranged from 0.41 to 8.9 ng/mL/mg. At baseline, patients' kidney function was comparable. In the multivariable linear mixed‐effects model, fast metabolisers ( C 0 / D ratio ≤1.53) had a significantly lower eGFR compared to slow metabolisers ( C 0 / D ratio >2.27) (−6.8 mL/min/1.73 m 2 , 95% CI −11.2, −2.4, p = 0.002). This association was confirmed when utilizing the individual median C 0 / D ratio as a continuous variable: for each 1 unit increase in the C 0 / D ratio there was a 2.8 mL/min/1.73 m 2 (95% CI 1.0, 4.5) increase in eGFR ( P = 0.002). Conclusion Fast tacrolimus metabolism is significantly associated with worse kidney function in HT recipients in the first 5 years post‐HT when compared to recipients with intermediate and slow tacrolimus metabolism.