Abstract: SA-PO072
Obesity Aggravates Ischemia-Reperfusion Injury (IRI)-Induced AKI in Mice
Session Information
- AKI: Mechanisms - III
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Da silva, Igor Oliveira, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
- De Menezes, Nicole Kawakami, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
- Jacobina, Heloisa de Oliveira, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
- Parra, Antonio Carlos, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
- Souza, Felipe Lima, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
- De Castro, Leticia U., University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
- Roelofs, Joris, University of Amsterdam, Amsterdam, Netherlands
- Tammaro, Alessandra, University of Amsterdam, Amsterdam, Netherlands
- Sanches, Talita R. C., University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
- Andrade, Lucia, University of Sao Paulo School of Medicine, Sao Paulo, Sao Paulo, Brazil
Background
Obesity, which is becoming increasingly common worldwide, is known to be associated with cardiovascular disease and progression of chronic kidney disease, due to inappropriate activation of the renin-angiotensin system. Many angiotensin II effects are dependent on AT1 stimulation of reactive oxygen species (ROS). In COVID-19 patients, overweight and obesity are associated with acute respiratory distress syndrome and AKI. Although obesity increases oxidative stress, endothelial dysfunction and inflammation, its effect on IRI-induced AKI is unknown. We hypothesized that obesity would aggravate renal IRI in mice.
Methods
We fed mice a high-fat or standard diet (45 and 10 kcal% fat, respectively) for 8 weeks. Some then underwent bilateral 30-min clamping of the kidney hila and subsequent reperfusion (groups: obese, normal, obese+IRI and normal+IRI). All studies were performed 48 h after IRI. Data are mean±SEM.
Results
Body weight (g) was 33±1.7, 32±0.7, 27±1.4 and 26±0.9 in the obese, obese+IRI, normal and normal+IRI groups, respectively (P<0.001). Mortality was 42% and 25% in the obese+IRI and normal+IRI groups, respectively (P <0.05); there were no deaths in the non-IRI groups. Serum glucose and cholesterol did not differ among the groups. Creatinine clearance (mL/min/100g BW) was 0.20±0.05 and 0.20±0.07 in the obese+IRI and normal+IRI groups, respectively, vs. 0.34±0.06 and 0.40±0.08 in the obese and normal groups, respectively. Renal p65 protein expression (%) was 127±4.8 in the obese+IRI group, vs. 100±4.1, 92.5±4.8 and 107±3.7, respectively, in the normal, obese and normal+IRI groups (P<0.05).
Conclusion
In obese individuals with AKI, ROS could be a therapeutic target (FAPESP, NWO).
Biochemistry, Histology and Protein expression
| Normal | Obese | Normal+IRI | Obese+IRI | |
| Urine osmolality (mOsm/kg) | 1669±625 | 2648±173 | 1557±144 | 1084±156α |
| Urinary TBARS (nmol/mL) | 530±113 | 995±196 | 723±92 | 1145±158β |
| Tubular injury score | 0.00 | 0.00 | 0.35±0.26 | 1.5±0.62α |
| Caspase (% of normal) | 90±4.5 | 116±5.6 | 144±9.4α | 183±14α,γ |
| AT1 (% of the Normal) | 99±5.6 | 116±9.1 | 107±14 | 163±15α,γ |
TBARS: thiobarbituric acid reactive substances. α P<0.05 vs. Normal and Obese; β P<0.05 vs. Normal; γ P<0.05 vs. Normal+IRI.
Funding
- Government Support – Non-U.S.