Kidney physiology and susceptibility to acute kidney injury: implications for renoprotection

Item Type:	Review
Title:	Kidney physiology and susceptibility to acute kidney injury: implications for renoprotection
Creators Name:	Scholz, H. and Boivin, F.J. and Schmidt-Ott, K.M. and Bachmann, S. and Eckardt, K.U. and Scholl, U.I. and Persson, P.B.
Abstract:	Kidney damage varies according to the primary insult. Different aetiologies of acute kidney injury (AKI), including kidney ischaemia, exposure to nephrotoxins, dehydration or sepsis, are associated with characteristic patterns of damage and changes in gene expression, which can provide insight into the mechanisms that lead to persistent structural and functional damage. Early morphological alterations are driven by a delicate balance between energy demand and oxygen supply, which varies considerably in different regions of the kidney. The functional heterogeneity of the various nephron segments is reflected in their use of different metabolic pathways. AKI is often linked to defects in kidney oxygen supply, and some nephron segments might not be able to shift to anaerobic metabolism under low oxygen conditions or might have remarkably low basal oxygen levels, which enhances their vulnerability to damage. Here, we discuss why specific kidney regions are at particular risk of injury and how this information might help to delineate novel routes for mitigating injury and avoiding permanent damage. We suggest that the physiological heterogeneity of the kidney should be taken into account when exploring novel renoprotective strategies, such as improvement of kidney tissue oxygenation, stimulation of hypoxia signalling pathways and modulation of cellular energy metabolism.
Keywords:	Acute Kidney Injury, Cell Hypoxia, Disease Susceptibility, Energy Metabolism, Gene Expression, Kidney, Mitochondria, Oxygen, PPAR gamma, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals
Source:	Nature Reviews Nephrology
ISSN:	1759-5061
Publisher:	Nature Publishing Group
Volume:	17
Number:	5
Page Range:	335-349
Date:	May 2021
Official Publication:	https://doi.org/10.1038/s41581-021-00394-7
PubMed:	View item in PubMed

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