Acute Kidney Injury Results in Long-Term Diastolic Dysfunction That Is Prevented by Histone Deacetylase Inhibition

Area of Science:

• Cardiovascular Science
• Nephrology
• Pharmacology

Background:

• Epidemiological studies link acute kidney injury (AKI) to increased long-term cardiovascular disease risk.
• Understanding the cardiorenal outcomes after AKI is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the long-term cardiorenal consequences of bilateral ischemia-reperfusion induced AKI in a mouse model.
• To evaluate the therapeutic potential of the histone deacetylase inhibitor ITF2357 on cardiorenal outcomes post-AKI.

Main Methods:

• A 1-year study was conducted in male mice subjected to bilateral ischemia-reperfusion injury.
• Cardiac function, blood pressure, and kidney fibrosis were assessed.
• Mice were treated with the histone deacetylase inhibitor ITF2357.

Main Results:

• AKI induced long-term cardiac metabolic dysfunction, diastolic dysfunction, and hypertension in mice.
• ITF2357 treatment preserved cardiac function and maintained normotension throughout the 1-year study period.
• ITF2357 did not prevent the development of kidney fibrosis following AKI.

Conclusions:

• AKI results in persistent cardiac dysfunction and metabolic alterations, contributing to cardiovascular morbidity.
• ITF2357 demonstrates potential in mitigating long-term cardiac complications of AKI but does not affect renal fibrosis.
• Targeting epigenetic modifications may offer a strategy to improve cardiorenal outcomes after AKI.