Maaike R Schagen, Teun B Petersen, Boris C A Seijkens, Jasper J Brugts, Kadir Caliskan, Alina A Constantinescu, Brenda C M de Winter, Isabella Kardys, Dennis A Hesselink, Olivier Manintveld
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引用次数: 0
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.
期刊介绍:
Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology features papers and reports on all aspects of drug action in humans: review articles, mini review articles, original papers, commentaries, editorials and letters. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. It also publishes research on new methods, new drugs and new approaches to treatment. The Journal is recognised as one of the leading publications in its field. It is online only, publishes open access research through its OnlineOpen programme and is published monthly.