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Kidney Week

Abstract: FR-PO991

Repeated Episodes of Ischemia/Reperfusion Induced Hemoxigenase-1 (HO-1) and Anti-Inflammatory Reactivity and Protect Against Chronic Kidney Injury

Session Information

  • CKD: Pathobiology - I
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Ortega-Trejo, Juan Antonio, Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico
  • Pérez-Villalva, Rosalba, Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico
  • Sanchez Navarro, Andrea, Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico
  • Bobadilla, Norma, Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico
Background

Repeated episodes of ischemia/reperfusion (IR) induce protection against acute kidney injury (AKI), but their long-term effects are unknown. This study was designed to evaluate the transition to chronic kidney disease (CKD) after three moderate and three severe episodes of IR compared to a single episode of IR.

Methods

AKI was induced in male Wistar rats that received a single IR (1IR) or three episodes of IR separated by an interval of 10 days (3IR) of moderate (20 min, n=8) or severe (45 min, n=8) bilateral renal ischemia, in both cases, sham operated groups were included (n=6). AKI to CKD transition was evaluated after 9 months. The immediate effects of IR were studied in another set of experiments done 24 h after in the 1IR group (n=5) and after the last IR in the 3IR group (n=8).

Results

IR induced AKI that improved before the next episode of IR in the 3IR group. During the subsequent 9-months, the 1IR group (underwent moderate or severe IR) developed CKD, evidenced by progressive proteinuria and renal fibrosis. In contrast, the late adverse effects of IR were markedly ameliorated in the 3IR groups. The immediate response after the 3rd IR episode was a robust increment in the expression of hemoxygenase-1 (HO-1), IL-10, TGF-β and CD206 positive infiltrating cells, and a decrease of IL-6, TNF-α, and phosphorylation of NFκB-p65. Interestingly, most CD206 positive cells co-localized with HO-1 in the interstitium. These results contrasted with the response to a single IR episode. In addition, repeated episodes of IR downregulated the expression of CHOP and BiP, endoplasmic reticulum (ER) stress markers.

Conclusion

AKI induced by IR results in progressive CKD. Repeated episodes of IR induced overexpression of HO-1, anti-inflammatory activity, reduced RE stress and long-term renal protection.