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

https://doi.org/10.1016/j.jacbts.2020.11.013Get rights and content
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Highlights

  • This is the first long-term (1-year) study to evaluate both the kidney and systemic sequelae of acute kidney injury in mice.

  • Serial kidney function was measured via transcutaneous glomerular filtration rate.

  • AKI resulted in diastolic dysfunction, followed by hypertension. Ejection fraction was preserved. One year after AKI, cardiac ATP levels were reduced compared with sham controls.

  • Mice treated with the histone deacetylase inhibitor, ITF2357, maintained normal diastolic function normal blood pressure, and normal cardiac ATP after AKI.

  • Metabolomics data suggest that treatment with ITF2357 preserves pathways related to energy metabolism.

Summary

Growing epidemiological data demonstrate that acute kidney injury (AKI) is associated with long-term cardiovascular morbidity and mortality. Here, the authors present a 1-year study of cardiorenal outcomes following bilateral ischemia-reperfusion injury in male mice. These data suggest that AKI causes long-term dysfunction in the cardiac metabolome, which is associated with diastolic dysfunction and hypertension. Mice treated with the histone deacetylase inhibitor, ITF2357, had preservation of cardiac function and remained normotensive throughout the study. ITF2357 did not protect against the development of kidney fibrosis after AKI.

Key Words

acute kidney injury
cardiorenal syndrome
diastolic dysfunction
histone deacetylase inhibition
systemic sequelae of kidney disease

Abbreviations and Acronyms

AKI
acute kidney injury
ATP
adenosine triphosphate
BUN
blood urea nitrogen
HDACi
histone deacetylase inhibitor
MAP
mean arterial pressure
PSR
picrosirius red
SCr
serum creatinine
tGFR
transcutaneous glomerular filtration rate

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