Failure to Sense Energy Depletion May Be a Novel Therapeutic Target in Chronic Kidney Disease (image) Tokyo Medical and Dental University Share Print E-Mail Caption In a mouse model of CKD, metabolome analysis confirmed a decrease in AMPK activation in the kidneys despite a high AMP: ATP ratio, suggesting that AMP K did not sense energy depletion. Several uremic factors were shown to inactivate AMP K in vitro and in ex vivo preparations of kidney tissue. The specific AMPK activator A-769662, which bypasses the AMP sensing mechanism, ameliorated fibrosis and improved energy status in the kidneys of CKD mice, whereas an AMP analog did not. We further demonstrated that a low-protein diet activated AMPK independent of the AMP sensing mechanism, leading to improvement in energy metabolism and kidney fibrosis. Credit Department of Nephrology,TMDU Usage Restrictions None Share Print E-Mail Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.