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Observational Study
. 2018 Jun;43(3):311-320.
doi: 10.1007/s13318-017-0453-7.

Association of Whole Blood Tacrolimus Concentrations with Kidney Injury in Heart Transplantation Patients

Maaike A Sikma  1 , Claudine C Hunault  2 , Johannes H Kirkels  3 , Marianne C Verhaar  4 , Jozef Kesecioglu  5 , Dylan W de Lange  6
Affiliations
Observational Study

Association of Whole Blood Tacrolimus Concentrations with Kidney Injury in Heart Transplantation Patients

Maaike A Sikma et al. Eur J Drug Metab Pharmacokinet. 2018 Jun.

Abstract

Background and objectives: Acute kidney injury (AKI) is frequently observed after heart transplantation and is associated with morbidity and mortality. However, many confounding factors also contribute to the development of AKI in heart transplants. We hypothesized that supratherapeutic whole-blood tacrolimus trough concentrations are associated with AKI.

Methods: In a retrospective observational cohort from April 2005 to December 2012, all adult heart transplantation patients were included. AKI was assessed in the first 2 weeks after transplantation as classified by the Kidney Disease Improving Global Outcomes Network (KDIGO). Whole-blood tacrolimus trough concentrations were determined from day 1 to day 14 and at 1, 3, 6 and 12 months post-transplantation. The therapeutic range was 9 to 15 ng/ml in the first 2 months and tapered to 5-8 ng/ml thereafter. The relationship between supratherapeutic tacrolimus trough concentrations and AKI was evaluated. The impact of various potentially confounding factors on tacrolimus concentrations and AKI was considered.

Results: We included 110 patients. AKI occurred in 57% of patients in the first week. Recovery from AKI was seen in 24%. The occurrence of chronic kidney disease (CKD) was 19% at 1 year. Whole-blood tacrolimus trough concentrations were often supratherapeutic and, despite correction for confounding factors, independently associated with AKI (OR 1.66; 95% CI 1.20-2.31).

Conclusions: Supratherapeutic whole-blood tacrolimus trough concentrations are independently associated with the development of AKI in adult heart transplantation patients. More stringent dosing of tacrolimus early after transplantation may be critical in preserving the kidney function.

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Conflict of interest statement

Ethics

This study was conducted in compliance with the Declaration of Helsinki, Good Clinical Practice guidelines and in accordance with local and national regulatory requirements and laws. The accredited ethics committee of the University Medical Center Utrecht has approved of the use of patient data (IRB UMC Utrecht protocol number 12-071).

Disclosure of interest

Claudine C. Hunault, Marianne C. Verhaar, Johannes H. Kirkels, Jozef Kesecioglu and Dylan W. de Lange declare that they have no conflicts of interest.

Funding

No source of funding was used to conduct this study.

Figures

Fig. 1
Fig. 1
Tukey boxplot of creatinine between day 1 and year 1. Day 0 is baseline creatinine. Box: 25th, median and 75th percentiles, whiskers: maximum value excluding outliers, dots: outliers more or less than 3/2 upper or lower quartile
Fig. 2
Fig. 2
Tukey boxplot of whole-blood tacrolimus trough concentrations between day 1 and year 1. The therapeutic range of 9–15 ng/ml and 5–8 ng/ml is indicated as gray bars in the figure. Box: 25th, median and 75th percentiles, whiskers: maximum value excluding outliers, dots: outliers more or less than 3/2 upper or lower quartile
See this image and copyright information in PMC

References

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