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The tacrolimus concentration-to-dose ratio is associated with kidney function in heart transplant recipients
Maaike R Schagen1, Teun B Petersen2,3, Boris C A Seijkens4
1Department of Internal Medicine, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Insights
Fast tacrolimus metabolism is linked to poorer kidney function in heart transplant recipients within five years post-transplant. This highlights the importance of monitoring tacrolimus levels to preserve kidney health in these patients.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Heart transplantation (HT) is often complicated by chronic kidney disease.
- Tacrolimus-induced nephrotoxicity is a significant contributor to this complication.
- Fast tacrolimus metabolism, indicated by a low concentration-to-dose (C0/D) ratio, is associated with impaired kidney function in other transplant recipients.
Purpose of the Study:
- To investigate the association between the tacrolimus concentration-to-dose (C0/D) ratio and kidney function in heart transplant (HT) recipients.
- To determine if fast tacrolimus metabolism impacts kidney function post-HT.
Main Methods:
- Retrospective study of 209 HT recipients using immediate-release tacrolimus.
- Assessed tacrolimus C0/D ratio and estimated glomerular filtration rate (eGFR) at multiple time points up to 60 months post-HT.
- Categorized patients into fast, intermediate, and slow tacrolimus metabolizers based on median C0/D ratio and used linear mixed-effects models to analyze eGFR.
Main Results:
- Fast metabolizers (C0/D ratio ≤1.53) exhibited significantly lower eGFR compared to slow metabolizers (C0/D ratio >2.27).
- A decrease of -6.8 mL/min/1.73 m² in eGFR was observed in fast metabolizers.
- Each 1 unit increase in the continuous C0/D ratio correlated with a 2.8 mL/min/1.73 m² increase in eGFR, confirming the association.
Conclusions:
- Fast tacrolimus metabolism is significantly associated with worse kidney function in heart transplant recipients during the first five years after transplantation.
- This finding suggests that tacrolimus metabolism rate is a critical factor influencing kidney outcomes in HT patients.
- Monitoring and potentially adjusting tacrolimus dosing based on metabolic status may be crucial for preserving kidney function.
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.
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