May 23, 2023

Treating kidney injury before it happens

Pretreatment of an animal model with a novel compound called PHAD reduced kidney injury, suggesting it may be a good candidate for preventing kidney injury in surgical patients.

Acute kidney injury (AKI) occurs in 12% of patients after noncardiac surgery and in up to 40% of patients post cardiac surgery.

While there are not any reliable FDA-approved ways to prevent AKI post-surgery, Antonio Hernandez, MD, Edward Sherwood, PhD, MD, Mark de Castecker, MBBS, PhD, and colleagues are hoping to change this with their novel pretreatment strategy.

The researchers used a synthetic agonist (PHAD) to activate toll-like receptor 4 (TLR4), a transmembrane protein that can induce an innate immune response, as a pretreatment in a mouse model of renal ischemia-reperfusion injury. TLR4 agonists have been shown to protect against organ injury. 

Compared to control animals, pretreatment with PHAD reduced renal injury as evidenced by lower creatine levels, interstitial edema and markers of kidney tubule injury.

This work, published May 1 in the American Journal of Physiology-Renal Physiology, represents a new modality for kidney injury prevention for surgical patients, the researchers concluded. PHAD is a good candidate for pharmaceutical development.

Co-authors of the paper are Naeem Patil, MBBS, PhD, Maya Brewer, Rachel Delgado, Lauren Himmel, DVM, PhD, Lauren Lopez, Julia Bohannon, PhD, and Allison Owen, PhD.

The research was supported by National Institutes of Health grants GM123345, GM108554, GM141927, AI151210, DK126122, DK112688, and the Department of Defense.