ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

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
 NormalObeseNormal+IRIObese+IRI
Urine osmolality (mOsm/kg)1669±6252648±1731557±1441084±156α
Urinary TBARS (nmol/mL)530±113995±196723±921145±158β
Tubular injury score0.000.000.35±0.261.5±0.62α
Caspase (% of normal)90±4.5116±5.6144±9.4α183±14α,γ
AT1 (% of the Normal)99±5.6116±9.1107±14163±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.