Early Tacrolimus Concentrations After Lung Transplant are Predicted by Combined Clinical and Genetic Factors and Associated with Acute Kidney Injury.

08:00 EDT 12th September 2019 | BioPortfolio

Summary of "Early Tacrolimus Concentrations After Lung Transplant are Predicted by Combined Clinical and Genetic Factors and Associated with Acute Kidney Injury."

Tacrolimus exhibits unpredictable pharmacokinetics after lung transplant, partly explained by CYP-enzyme polymorphisms. However, whether exposure variability during the immediate post-operative period affects outcomes is unknown, and pharmacogenetic dosing may be limited by residual pharmacokinetic variability. We estimated adjusted associations between early post-operative tacrolimus concentrations and acute kidney injury (AKI) and acute cellular rejection (ACR), and identified clinical and pharmacogenetic factors that explain post-operative tacrolimus concentration variability in 484 lung transplant patients. Increasing tacrolimus concentration was associated with higher AKI risk: HR 1.54, (95%CI 1.20-1.96) per 5-mg/dL, and increasing AKI severity (OR 1.29 (1.04-1.60) per 5-mg/dL, but not
HR 1.02 (95%CI 0.73-1.42). A model with clinical and pharmacogenetic factors explained 42% of concentration variance compared to 19% for pharmacogenetic factors only. Early tacrolimus exposure was independently associated with AKI after lung transplantation, but not ACR. Clinical factors accounted for substantial residual tacrolimus concentration variability not explained by CYP-enzyme polymorphisms.


Journal Details

This article was published in the following journal.

Name: Clinical pharmacology and therapeutics
ISSN: 1532-6535


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