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
Online-Zugang:Volltext
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Abstract [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.
AbstractList Visual Abstract
• 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.
[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.
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.
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.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.
Author Soranno, Danielle E.
Ding, Kathy
Gist, Katja M.
McKinsey, Timothy A.
Wennersten, Sara A.
Altmann, Christopher
Bagchi, Rushita A.
Baker, Peter
Steinkühler, Christian
Haefner, Korey R.
Montford, John R.
Faubel, Sarah
Kirkbride-Romeo, Lara
Keith, Brysen
Cavasin, Maria A.
Author_xml – sequence: 1
  givenname: Danielle E.
  surname: Soranno
  fullname: Soranno, Danielle E.
  email: Danielle.Soranno@childrenscolorado.org
  organization: Department of Pediatrics, Pediatric Nephrology, University of Colorado, Aurora, Colorado, USA
– sequence: 2
  givenname: Lara
  surname: Kirkbride-Romeo
  fullname: Kirkbride-Romeo, Lara
  organization: Department of Pediatrics, Pediatric Nephrology, University of Colorado, Aurora, Colorado, USA
– sequence: 3
  givenname: Sara A.
  surname: Wennersten
  fullname: Wennersten, Sara A.
  organization: Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
– sequence: 4
  givenname: Kathy
  surname: Ding
  fullname: Ding, Kathy
  organization: Department of Pediatrics, Pediatric Nephrology, University of Colorado, Aurora, Colorado, USA
– sequence: 5
  givenname: Maria A.
  surname: Cavasin
  fullname: Cavasin, Maria A.
  organization: Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
– sequence: 6
  givenname: Peter
  surname: Baker
  fullname: Baker, Peter
  organization: Department of Pediatrics, Clinical Genetics and Metabolism, University of Colorado, Aurora, Colorado, USA
– sequence: 7
  givenname: Christopher
  surname: Altmann
  fullname: Altmann, Christopher
  organization: Department of Medicine, Division of Renal Disease and Hypertension, University of Colorado, Aurora, Colorado, USA
– sequence: 8
  givenname: Rushita A.
  surname: Bagchi
  fullname: Bagchi, Rushita A.
  organization: Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
– sequence: 9
  givenname: Korey R.
  surname: Haefner
  fullname: Haefner, Korey R.
  organization: Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
– sequence: 10
  givenname: Christian
  surname: Steinkühler
  fullname: Steinkühler, Christian
  organization: Italfarmaco, Milan, Italy
– sequence: 11
  givenname: John R.
  surname: Montford
  fullname: Montford, John R.
  organization: Department of Medicine, Division of Renal Disease and Hypertension, University of Colorado, Aurora, Colorado, USA
– sequence: 12
  givenname: Brysen
  surname: Keith
  fullname: Keith, Brysen
  organization: Department of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
– sequence: 13
  givenname: Katja M.
  surname: Gist
  fullname: Gist, Katja M.
  organization: Department of Pediatrics, Pediatric Cardiology, University of Colorado, Aurora, Colorado, USA
– sequence: 14
  givenname: Timothy A.
  surname: McKinsey
  fullname: McKinsey, Timothy A.
  organization: Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
– sequence: 15
  givenname: Sarah
  surname: Faubel
  fullname: Faubel, Sarah
  organization: Department of Medicine, Division of Renal Disease and Hypertension, University of Colorado, Aurora, Colorado, USA
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33665513$$D View this record in MEDLINE/PubMed
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Issue 2
Keywords 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
Language English
License This is an open access article under the CC BY-NC-ND license.
2021 The Authors.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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Snippet [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...
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Growing epidemiological data demonstrate that acute kidney injury (AKI) is associated with long-term cardiovascular morbidity and mortality. Here, the authors...
• 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...
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StartPage 119
SubjectTerms acute kidney injury
cardiorenal syndrome
Cardiovascular
diastolic dysfunction
histone deacetylase inhibition
Preclinical Research
systemic sequelae of kidney disease
Title Acute Kidney Injury Results in Long-Term Diastolic Dysfunction That Is Prevented by Histone Deacetylase Inhibition
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https://dx.doi.org/10.1016/j.jacbts.2020.11.013
https://www.ncbi.nlm.nih.gov/pubmed/33665513
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