en
Scientific article
Review
English

Hypoxia in chronic kidney disease: towards a paradigm shift?

Publication date2020
Abstract

Chronic kidney disease (CKD) is defined as an alteration of kidney structure and/or function lasting for >3 months [1]. CKD affects 10% of the general adult population and is responsible for large healthcare costs [2]. Since the end of the last century, the role of hypoxia in CKD progression has controversially been discussed. To date, there is evidence of the presence of hypoxia in late-stage renal disease, but we lack time-course evidence, stage correlation and also spatial co-localization with fibrotic lesions to ensure its causative role. The classical view of hypoxia in CKD progression is that it is caused by peritubular capillary alterations, renal anaemia and increased oxygen consumption regardless of the primary injury. In this classical view, hypoxia is assumed to further induce pro-fibrotic and pro-inflammatory responses, as well as oxidative stress, leading to CKD worsening as part of a vicious circle. However, recent investigations tend to question this paradigm, and both the presence of hypoxia and its role in CKD progression are still not clearly demonstrated. Hypoxia-inducible factor (HIF) is the main transcriptional regulator of the hypoxia response. Genetic HIF modulation leads to variable effects on CKD progression in different murine models. In contrast, pharmacological modulation of the HIF pathway [i.e. by HIF hydroxylase inhibitors (HIs)] appears to be generally protective against fibrosis progression experimentally. We here review the existing literature on the role of hypoxia, the HIF pathway and HIF HIs in CKD progression and summarize the evidence that supports or rejects the hypoxia hypothesis, respectively.

Keywords
  • Chronic kidney disease
  • HIF
  • Hypoxia
  • Hydroxylase inhibitor
  • PHI
Funding
Citation (ISO format)
FAIVRE, Anna, SCHOLZ, Carsten C, DE SEIGNEUX MATTHEY, Sophie. Hypoxia in chronic kidney disease: towards a paradigm shift? In: Nephrology Dialysis Transplantation, 2020, p. gfaa091. doi: 10.1093/ndt/gfaa091
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Article (Published version)
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ISSN of the journal1460-2385
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