Determining Risk Factors for Triple Whammy AKI using Computational Models of Long - Term Blood Pressure Regulation

Concurrent use of diuretics, angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), and nonsteroidal anti‐inflammatory drugs (NSAIDs) increases the risk of acute kidney injury (AKI). AKI resulting from use of all three drugs is referred to as “triple whammy”. Diuretics and ACEI/ARB are often prescribed in tandem for the treatment of hypertension while some NSAIDs, such as ibuprofen, are available over the counter. As such, concurrent treatment with all three drugs is common. To address the critical need to better understand the mechanisms behind the increased risk of AKI and to identify potential risk factors, we use computational models of long‐term blood pressure regulation we developed previously. We hypothesize that individual variations in tubuloglomerular feedback, renal sympathetic nervous activity, and vasoactive hormones such as angiotensin II will determine whether or not triple whammy patients develop AKI. Other circumstances that we hypothesize to influence AKI development include hypertension, salt ingestion and sensitivity, and genetic polymorphisms in enzymes (ACE) or receptors (angiotensin type 1). The computational models used include variables describing the heart and circulation, kidney function, sodium and water reabsorption in the nephron, and the renin angiotensin system (RAS) and is fit separately for male and female humans. Support or Funding Information This research was supported by the Canada 150 Research Chair program and by the National Institutes of Health: National Institute of Diabetes and Digestive and Kidney Diseases, grant R01DK106102. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .