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Kidney Week

Abstract: PO0147

Sex as a Biological Variable in Cardiac Outcomes after AKI in Mice

Session Information

  • AKI Mechanisms - 1
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Soranno, Danielle, University of Colorado, Denver, Colorado, United States
  • Kirkbride-Romeo, Lara A., University of Colorado, Denver, Colorado, United States
  • Altmann, Chris, University of Colorado, Denver, Colorado, United States
  • Baker, Peter R., University of Colorado, Denver, Colorado, United States
  • Faubel, Sarah, University of Colorado, Denver, Colorado, United States
Background

Acute kidney injury (AKI) is common in patients, and predisposes patients to cardiovascular disease. Estrogen is known to protect against ischemic AKI, however it is unknown whether it also protects against the cardiac sequelae of AKI. We report a 1 year study evaluating the cardiac and metabolic effects of bilateral renal ischemia-reperfusion injury in male and female C57BL/6 mice.

Methods

Males received 25 minutes of ischemia, while females received 34 minutes. Serial glomerular filtration rate (GFR), echocardiograms and blood pressure assessments were performed with sacrifice at 1 year. Plasma and cardiac metabolomics were measured. Mead’s resource calculation was utilized to calculate sample size of n = 5-11. Comparison between two groups was performed using unpaired t tests assuming Gaussian distribution with Welch’s correction, P < 0.05 for statistical significance.

Results

Serial measurements of GFR showed that the AKI model was matched between males and females throughout the 1 year study. Males with AKI developed diastolic dysfunction (quantified on echocardiogram data by E’/A’ <1), hypertension, reduced cardiac adenosine triphosphate (ATP) levels; females with AKI developed hypertension but not diastolic dysfunction and had normal cardiac ATP levels.

Conclusion

This is the first study to show chronic diastolic dysfunction after AKI and variations in cardiorenal outcomes with regards to sex. Diminished cardiac ATP is a known cause of diastolic dysfunction.

Figure 1. (A) 25 minutes of ischemia in males (AKIMales) and 34 minutes of ischemia in females (AKIFemales) results in a matched model of kidney injury with no statistically significant difference in normalized glomerular filtration rate measured over the 1 year study. (B) Males developed impaired diastolic function (E’ < A’) and hypertension after AKI. (C) Females maintained normal diastolic function after AKI, but did develop hypertension that resolved by 1 year. (D) 1 year after AKI, males had reduced levels of cardiac ATP whereas females did not.

Funding

  • NIDDK Support