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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Veröffentlicht in:JACC. Basic to translational science Jg. 6; H. 2; S. 119 - 133
Hauptverfasser: 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
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Elsevier Inc 01.02.2021
Elsevier
Schlagworte:
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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Zusammenfassung:[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.
Bibliographie: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