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.