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

[Display omitted] •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...

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Vydáno v:	JACC. Basic to translational science Ročník 6; číslo 2; s. 119 - 133
Hlavní autoři:	Soranno, Danielle E., Kirkbride-Romeo, Lara, Wennersten, Sara A., Ding, Kathy, Cavasin, Maria A., Baker, Peter, Altmann, Christopher, Bagchi, Rushita A., Haefner, Korey R., Steinkühler, Christian, Montford, John R., Keith, Brysen, Gist, Katja M., McKinsey, Timothy A., Faubel, Sarah
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Elsevier Inc 01.02.2021 Elsevier
Témata:	acute kidney injury cardiorenal syndrome Cardiovascular diastolic dysfunction histone deacetylase inhibition Preclinical Research systemic sequelae of kidney disease SCr histone deacetylase inhibition tGFR PSR cardiorenal syndrome diastolic dysfunction systemic sequelae of kidney disease acute kidney injury BUN ATP HDACi MAP AKI transcutaneous glomerular filtration rate mean arterial pressure blood urea nitrogen serum creatinine picrosirius red histone deacetylase inhibitor adenosine triphosphate SCr, serum creatinine PSR, picrosirius red HDACi, histone deacetylase inhibitor AKI, acute kidney injury MAP, mean arterial pressure tGFR, transcutaneous glomerular filtration rate ATP, adenosine triphosphate BUN, blood urea nitrogen
ISSN:	2452-302X, 2452-302X
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Shrnutí:	[Display omitted] •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. 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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2452-302X 2452-302X
DOI:	10.1016/j.jacbts.2020.11.013