ABSTRACT
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. Method(s): 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. Result(s): 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(s): In obese individuals with AKI, ROS could be a therapeutic target (FAPESP, NWO).