ESPN 53rd Annual Meeting

ESPN 2021


 
Characterization of acute kidney injury in the setting of acute myocardial infarction in mice
Nada J. Habeichi 2 Jad Degheili 4 Rana Ghali 3 Sami Sanjad 4 Mathias Mericskay 1 Mohamed Khaled 7 George W. Booz 1 Fouad A. Zouein 5 Bilal Aoun 4

1- AMERICAN UNIVERSITY OF BEIRUT MEDICAL CENTER
2- INSERM Department of Signaling and Cardiovascular Pathophysiology-UMR-S1180, University Paris-Saclay, Ch√Ętenay-Malabry
3- Institut National de la Sante et de la Recherche Medicale (Inserm), Unit 970, Paris Cardiovascular Research Center, 75015 Paris, France
4- Department of Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
5- Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
6- Department of Pharmacology and Toxicology, School of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
7- Montfermeil hospital, Department of Pediatrics and adolescent medecin, Montfermeil, France
 
Introduction:

Cardiovascular diseases remain the leading cause of death worldwide. Epidemiological studies report that 4 out of 5 CVD related deaths are attributable to acute myocardial infarction (AMI) and ischemic diseases. Around 25% of patients with AMI progress not only to heart failure but also acute kidney injury (AKI) through the cardiorenal interrelationship, increasing mortality rate significantly.

Material and methods:

In this study, we aimed at characterizing AKI as early as 4 and 7 days post-MI. 3 months old C57BLB/J male mice were enrolled in this study and divided into 2 groups: Control and MI. Mice were sacrificed 4 and 7 days post-MI. Kidney functional, structural, and molecular changes were evaluated. 

Results:

Cardiac hemodynamic analysis showed a significant decrease in ejection fraction (EF) and cardiac output (CO) at 4 and 7 days post-MI. EF dropped from 54.202±1.336% to 25.502±3.529% and from 56.289±1.481% to 30.774±2.371% post-MI at 4 and 7 days respectively. CO dropped from 0.914±0.044 ml/min to 0.450±0.024 ml/min and 0.953±0.120 ml/min to 0.667±0.076 ml/min post-MI at 4 and 7 days respectively. Urine output, a marker of acute kidney injury substantially decreased from 2175±213.6 ml/24h to 950±119.02 ml/24h and from 2333±2.2.78 ml/24h to 1260±136.38 ml/24h post-MI at 4 and 7 days respectively. Kidney histological alterations characterized by proximal convoluted tubule (PCT) dilatation and fibrosis markedly increased in MI mice. PCT dilatation increased from 699202.852±28622.352 AU to 839509.844±44501.25 AU and from 713231.66±24318.17 AU to 952155.38±38239.119 AU post-MI at 4 and 7 days respectively. Renal fibrosis increased from 2.201±0.127% to 7.341±1.735% and from 1.621±0.119% to 4.367±0.571% post-MI at 4 and 7 days respectively. α-smooth muscle actin (α-SMA), a well-known indicator of fibrosis, substantially increased in kidneys by 3.400± 0.704 and 2.852± 0.836 fold change post-MI at 4 and 7 days respectively.  The pro-inflammatory cytokine interleukin-1 significantly increased by 1.96±0.389 fold change in the kidneys of mice at day 7 post-MI only

Conclusions:

Our findings revealed enhanced AKI as early as 4 and 7 days post-MI. Further experiments are currently underway to decipher the molecular pathways involved in the observed damage.