Chronic environmental hypoxia attenuates innate immunity activation and renal injury in two CKD models

Author(s)

Zambom, Fernanda Florencia Fregnan ; Albino, Amanda Helen ; Tessaro, Helena Mendonca ; Foresto-Neto, Orestes ; Malheiros, Denise Maria Avancini Costa ; Camara, Niels Olsen Saraiva ; Zatz, Roberto

• Document type: Journal article
• Source: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY; v. 325, n. 3, p. 16-pg., 2023-09-01.

Abstract

Tissue hypoxia has been pointed out as a major pathogenic factor in chronic kidney disease (CKD). However, epidemiological and experimental evidence inconsistent with this notion has been described. We have previously reported that chronic exposure to low ambient Po-2 promoted no renal injury in normal rats and in rats with 5/6 renal ablation (Nx) unexpectedly attenuated renal injury. In the present study, we investigated whether chronic exposure to low ambient Po-2 would also be renoprotective in two additional models of CKD: adenine (ADE) excess and chronic nitric oxide (NO) inhibition. In both models, normobaric ambient hypoxia attenuated the development of renal injury and inflammation. In addition, renal hypoxia limited the activation of NF-?B and NOD-like receptor family pyrin domain containing 3 inflammasome cascades as well as oxidative stress and intrarenal infiltration by angiotensin II-positive cells. Renal activation of hypoxia-inducible factor (HIF)-2a, along with other adaptive mechanisms to hypoxia, may have contributed to these renoprotective effects. The present findings may contribute to unravel the pathogenesis of CKD and to the development of innovative strategies to arrest its progression. (AU)

• FAPESP's process: 12/10926-5 - Pathogenesis and treatment of chronic kidney disease: role of innate immunity in glomerular, tubular and interstitial injury
• Grantee: Roberto Zatz
• Support Opportunities: Research Projects - Thematic Grants