Determining Risk Factors for Triple Whammy Acute Kidney Injury: Sex-specific Modeling and Analysis

Concurrent use of a diuretic, a renin-angiotensin system (RAS) inhibitor,
and a nonsteroidal anti-inflammatory drug (NSAID) significantly increases
the risk of acute kidney injury (AKI). This phenomenon is known as 'triple
whammy'. Diuretics and RAS inhibitors, such as an angiotensin converting
enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), are often
prescribed in tandem for the treatment of hypertension, whereas some NSAIDs,
such as ibuprofen, are available over the counter. As such, concurrent
treatment with all three drugs is not uncommon. The goals of this study are
to better understand the mechanisms underlying the development of triple
whammy AKI and to identify physiological factors that may increase an
individual's susceptibility. To accomplish these goals, we utilize
computational models of long-term blood pressure regulation. We found that
individual variation in water intake or the myogenic response as well as
high dosages of these drugs may predispose triple whammy patients to develop AKI. The computational models used
include variables describing the heart and circulation, kidney function,
sodium and water reabsorption in the nephron and the RAS, and are
parameterized separately for men and women.