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Circadian rhythms and the kidney

Abstract

Numerous physiological functions exhibit substantial circadian oscillations. In the kidneys, renal plasma flow, the glomerular filtration rate and tubular reabsorption and/or secretion processes have been shown to peak during the active phase and decline during the inactive phase. These functional rhythms are driven, at least in part, by a self-sustaining cellular mechanism termed the circadian clock. The circadian clock controls different cellular functions, including transcription, translation and protein post-translational modifications (such as phosphorylation, acetylation and ubiquitylation) and degradation. Disruption of the circadian clock in animal models results in the loss of blood pressure control and substantial changes in the circadian pattern of water and electrolyte excretion in the urine. Kidney-specific suppression of the circadian clock in animals implicates both the intrinsic renal and the extrarenal circadian clocks in these pathologies. Alterations in the circadian rhythm of renal functions are associated with the development of hypertension, chronic kidney disease, renal fibrosis and kidney stones. Furthermore, renal circadian clocks might interfere with the pharmacokinetics and/or pharmacodynamics of various drugs and are therefore an important consideration in the treatment of some renal diseases or disorders.

Key points

  • Several renal functions, including renal plasma flow, glomerular filtration rate, tubular transport activities and diuresis, have circadian rhythms.

  • Molecular clocks partially drive these oscillations and act on most intracellular processes (such as DNA replication, transcription, translation, post-translational modifications, protein sorting and membrane targeting).

  • Disruption of the molecular clock in mice leads to blood pressure abnormalities and impairs the circadian rhythmicity of water and sodium homeostasis.

  • The involvement of circadian rhythms and molecular clocks in human renal diseases remains uncertain, but chronopharmacology is emerging as a key player in blood pressure control.

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Fig. 1: Molecular clocks in humans.
Fig. 2: Intrinsic circadian clocks in the kidneys.
Fig. 3: Intracellular circadian rhythms.

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Acknowledgements

The authors thank their students, postdoctoral fellows and technicians, who contributed substantially to the advancement of the field through their curiosity and hard work in the laboratory. The authors are supported by grants from the Swiss National Science Foundation (31003A-169493 to D.F. and 310030–163340 to O.B.).

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Firsov, D., Bonny, O. Circadian rhythms and the kidney. Nat Rev Nephrol 14, 626–635 (2018). https://doi.org/10.1038/s41581-018-0048-9

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