January 19, 2023

Low potassium injures kidney

Vanderbilt researchers have discovered that low dietary potassium causes direct kidney injury, suggesting potential new targets for treating chronic kidney disease.

Diets with a high sodium-to-potassium ratio are linked to poor cardiovascular outcomes. Attention has mostly focused on high sodium, but low potassium is also a culprit in cardiovascular disease. 

Andrew Terker, MD, PhD, and colleagues have now discovered that low dietary potassium also causes direct kidney injury. 

Using in vitro and in vivo approaches, the researchers demonstrated that the injury effects depend on the Kir4.2 potassium channel in kidney proximal tubule cells. Efflux of potassium from the cells caused intracellular acidosis and activated the enzyme glutaminase, leading to hypertrophy, inflammation and fibrosis. Deletion of Kir4.2 or glutaminase protected proximal tubule cells from injury in both cell culture and animal models. 

The findings, published in Cell Reports, identify Kir4.2 and glutaminase as mediators of low potassium-related kidney injury and potential therapeutic targets. The findings also suggest that the standard practice of recommending excessive restriction of dietary potassium for patients with chronic kidney disease could unintentionally contribute to disease progression in certain settings.

Ming-Zhi Zhang, MD, and Raymond Harris, MD, are co-corresponding authors with Terker of the Cell Reports study. Other authors include Yahua Zhang, MD, J.P. Arroyo, MD, PhD, Shirong Cao, MD, PhD, Suwan Wang, Xiaofeng Fan and Jerod Denton, PhD. 

The research was supported by the National Institutes of Health (grants OD033412, DK051265, DK095785, DK062794, DK007569, DK114809), Department of Veterans Affairs (Merit Award 00507969), Vanderbilt Center for Kidney Disease, Vanderbilt Diabetes Research and Training Center (NIH grant DK020593), and American Heart Association.