Abstract
Increasing evidence suggested the multifactorial nature of nocturia, but the true pathogenesis of this condition still remains to be elucidated. Contemporary clinical medications are mostly symptom based, aimed at either reducing nocturnal urine volume or targeting autonomic receptors within the bladder to facilitate urine storage. The day–night switch of the micturition pattern is controlled by circadian clocks located both in the central nervous system and in the peripheral organs. Arousal threshold and secretion of melatonin and vasopressin increase at night-time to achieve high-quality sleep and minimize nocturnal urine production. In response to the increased vasopressin, the kidney reduces the glomerular filtration rate and facilitates the reabsorption of water. Synchronously, in the bladder, circadian oscillation of crucial molecules occurs to reduce afferent sensory input and maintain sufficient bladder capacity during the night sleep period. Thus, nocturia might occur as a result of desynchronization in one or more of these circadian regulatory mechanisms. Disrupted rhythmicity of the central nervous system, kidney and bladder (known as the brain–kidney–bladder circadian axis) contributes to the pathogenesis of nocturia. Novel insights into the chronobiological nature of nocturia will be crucial to promote a revolutionary shift towards effective therapeutics targeting the realignment of the circadian rhythm.
Key points
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Growing evidence has shown that disrupted rhythmicity of the central nervous system, kidney and bladder (the brain–kidney–bladder circadian axis) contributes to the pathogenesis of nocturia.
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The daily rhythm of human behaviour and physiology is regulated by the transcription–translation feedback loop, which exists both in the brain and in peripheral metabolic tissues, consisting of opposite transcriptional activators (CLOCK and BMAL1) and repressors (PER and CRY).
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Disruption of the central clock in the suprachiasmatic nucleus and neuroendocrine system leads to nocturia through impaired sleep quality and misaligned release of hormones such as melatonin and arginine vasopressin.
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Most physiological renal processes, such as urine secretion and water reabsorption, follow a circadian pattern of activity; disruptions of this pattern can cause nocturia.
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The circadian expression of peripheral clock genes in the bladder leads to time-dependent variations of bladder sensation and excitability, which can be disorganized under pathophysiological conditions contributing to nocturia onset.
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Expanding knowledge of the molecular basis of circadian regulation and dysregulation within the brain–kidney–bladder circadian axis will help to develop strategies for the prevention, management and treatment of nocturia based on chronobiology.
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Song, QX., Suadicani, S.O., Negoro, H. et al. Disruption of circadian rhythm as a potential pathogenesis of nocturia. Nat Rev Urol 22, 276–293 (2025). https://doi.org/10.1038/s41585-024-00961-0
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DOI: https://doi.org/10.1038/s41585-024-00961-0
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