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Abstract: SA-PO582

Exercise Attenuates Ischemia–Reperfusion-Induced AKI

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Telles, Joao Paulo Mota, University of Sao Paulo School of Medicine, Sao Paulo, São PAULO, Brazil
  • Zanfra, Isabella Peres, University of Sao Paulo School of Medicine, Sao Paulo, São PAULO, Brazil
  • De Castro, Leticia U., University of Sao Paulo School of Medicine, Sao Paulo, São PAULO, Brazil
  • Duarte-Neto, Amaro N., University of Sao Paulo School of Medicine, Sao Paulo, São PAULO, Brazil
  • Condor Capcha, Jose Manuel, University of Sao Paulo School of Medicine, Sao Paulo, São PAULO, Brazil
  • Santinho, Mirela, University of Sao Paulo School of Medicine, Sao Paulo, São PAULO, Brazil
  • Andrade, Lucia, University of Sao Paulo School of Medicine, Sao Paulo, São PAULO, Brazil
Background

Aerobic (endurance) and strength (resistance) exercise have both been proven to be beneficial for patients with chronic kidney disease. Acute kidney injury continues to be the leading cause of death among critical care patients. We hypothesized that there is cross-talk between muscles and the kidneys and that exercise could attenuate the renal damage caused by ischemia–reperfusion. In this study, we assess the impact of exercise in rats submitted to renal ischemia–reperfusion injury (IRI).

Methods

Wistar rats were divided into two groups: Exer+IRI (n = 7), in which rats were submitted to a standardized protocol consisting in a treadmill run at up to 60% of the maximum calculated speed and climbing of a standardized ladder (30 min of running+10 climbs with tail weights, 5 times a week for 8 weeks), followed by bilateral clamping of the kidney hila (30 min) and subsequent reperfusion; and control+IRI (n = 6) in which the protocol consisted in a treadmill run at the lowest speed (30 min, 5 times a week for 8 weeks: control condition), bilateral clamping of the kidney hila (30 min), and subsequent reperfusion. All studies were performed 48 h after reperfusion. Data are mean ± SEM.

Results

Serum levels of urea were higher in control+IRI rats than in Exer+IRI rats (143 ± 43 vs. 92 ± 12 mg/dl), as were urinary levels of NGAL (46 ± 10.6 vs. 24 ± 5.6 μg/mg urinary creatinine, p < 0.05). In kidney tissue, protein expression of Toll-like receptor 4 (TLR4) was higher in control+IRI rats than in Exer+IRI rats (105 ± 2.4 vs. 67 ± 1.9%; p < 0.01). Renal protein expression of Klotho was lower in control+IRI rats than in Exer+IRI rats (99.5 ± 1.6 vs. 134 ± 6.7%; p < 0.01) as was protein expression of manganese superoxide dismutase (98.8 ± 2.2 vs. 122 ± 5.7%, p <0.01). Renal apoptosis (determined by TUNEL) was lower in Exer+IRI rats than in control+IRI rats (3.7 ± 0.8 vs. 11.5 ± 5.0 positive cells/0.087 mm2; p < 0.05). Acute tubular necrosis was more extensive in control+IRI rats than in Exer+IRI rats (5.3 ± 0.6 vs. 3.8 ± 0.4, p < 0.05), most control+IRI rats presenting damage in >50% of the tubular area, compared with <50% for the Exer+IRI rats.

Conclusion

Exercise attenuates renal IRI by decreasing TLR4 expression and is renoprotective in a Klotho-dependent manner. (FAPESP)

Funding

  • Government Support - Non-U.S.