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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
ACR:
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.

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This article was published in the following journal.

Name: Clinical pharmacology and therapeutics
ISSN: 1532-6535
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Medical and Biotech [MESH] Definitions

A 12-KDa tacrolimus binding protein that is found associated with and may modulate the function of calcium release channels. It is a peptidyl-prolyl cis/trans isomerase which is inhibited by both tacrolimus (commonly called FK506) and SIROLIMUS.

A family of immunophilin proteins that bind to the immunosuppressive drugs TACROLIMUS (also known as FK506) and SIROLIMUS. EC 5.2.1.-

A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that TACROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.

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Absence of air in the entire or part of a lung, such as an incompletely inflated neonate lung or a collapsed adult lung. Pulmonary atelectasis can be caused by airway obstruction, lung compression, fibrotic contraction, or other factors.

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