Failure to Sense Energy Depletion May Be a Novel Therapeutic Target in Chronic Kidney Disease (IMAGE)

Tokyo Medical and Dental University

Failure to Sense Energy Depletion May Be a Novel Therapeutic Target in Chronic Kidney Disease

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.

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Department of Nephrology,TMDU

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