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Circadian rhythms and renal pathophysiology
Rajesh Mohandas, … , Yogesh Scindia, Michelle L. Gumz
Rajesh Mohandas, … , Yogesh Scindia, Michelle L. Gumz
Published February 1, 2022
Citation Information: J Clin Invest. 2022;132(3):e148277. https://doi.org/10.1172/JCI148277.
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Review Article has an altmetric score of 42

Circadian rhythms and renal pathophysiology

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Abstract

The reality of life in modern times is that our internal circadian rhythms are often out of alignment with the light/dark cycle of the external environment. This is known as circadian disruption, and a wealth of epidemiological evidence shows that it is associated with an increased risk for cardiovascular disease. Cardiovascular disease remains the top cause of death in the United States, and kidney disease in particular is a tremendous public health burden that contributes to cardiovascular deaths. There is an urgent need for new treatments for kidney disease; circadian rhythm–based therapies may be of potential benefit. The goal of this Review is to summarize the existing data that demonstrate a connection between circadian rhythm disruption and renal impairment in humans. Specifically, we will focus on chronic kidney disease, lupus nephritis, hypertension, and aging. Importantly, the relationship between circadian dysfunction and pathophysiology is thought to be bidirectional. Here we discuss the gaps in our knowledge of the mechanisms underlying circadian dysfunction in diseases of the kidney. Finally, we provide a brief overview of potential circadian rhythm–based interventions that could provide benefit in renal disease.

Authors

Rajesh Mohandas, Lauren G. Douma, Yogesh Scindia, Michelle L. Gumz

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Figure 1

Transcription-translation feedback loop of the circadian clock.

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Transcription-translation feedback loop of the circadian clock.
BMAL1 an...
BMAL1 and CLOCK bind to E-box response elements in the promoters of target genes, which include Period and Cryptochrome. PER and CRY form the negative arm of this feedback loop. Ancillary loops of the transcription-translation feedback system involving nuclear receptors and posttranslational modifications exist but will not be discussed here. Also beyond the scope of this Review is a discussion of the non-canonical functions of clock proteins, such as the role of BMAL1 in the regulation of translation in the cytosol (161).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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