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

Year: 2025

Type: article

Abstract: 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 [C0/D] ratio), negatively affects kidney function. Here, the association between the C0/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 C0/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 C0/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 C0/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 (C0/D ratio ≤1.53) had a significantly lower eGFR compared to slow metabolisers (C0/D ratio >2.27) (−6.8 mL/min/1.73 m2, 95% CI −11.2, −2.4, p = 0.002). This association was confirmed when utilizing the individual median C0/D ratio as a continuous variable: for each 1 unit increase in the C0/D ratio there was a 2.8 mL/min/1.73 m2 (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.

Source: British Journal of Clinical Pharmacology

DOI: 10.1002/bcp.70041