275 - Circadian Rhythm Disturbances in Nocturia and Nocturnal Polyuria: A Systematic Review

Hypothesis / aims of study Nocturia and nocturnal polyuria are frequently observed in older adults and are known to significantly impact sleep quality and daily functioning. While these conditions have a complex and multifactorial origin, growing attention has been given to the possible influence of circadian rhythm disturbances—such as reduced nocturnal secretion of melatonin and vasopressin, or disruption of the sleep–wake cycle—on abnormal nighttime urine production. Although this connection is biologically plausible, it remains insufficiently studied. This review aims to assess the existing literature on the relationship between circadian rhythm disturbances and both the frequency and severity of nocturia and nocturnal polyuria in adults. By bringing together findings from varied clinical and research settings, it seeks to better understand the underlying mechanisms and explore whether circadian dysregulation might serve as a useful focus for future diagnostic or therapeutic strategies. Study design, materials and methods A systematic review was conducted following PRISMA guidelines. Databases searched included PubMed, Embase, and CINAHL, without any year restrictions. Inclusion criteria were studies on adults (≥18 years) experiencing nocturia (≥2 voids per night) or nocturnal polyuria (nocturnal polyuria index >33%), explicitly assessing circadian rhythm disturbances. Both observational and interventional studies were included. Two reviewers independently screened articles. Data on circadian rhythm parameters (e.g., melatonin, vasopressin), nocturnal urine output, sleep quality, and associated biomarkers were extracted. The Newcastle–Ottawa Scale was used to assess the risk of bias. Results From an initial search yielding 635 articles, 15 were ultimately selected based on eligibility criteria. The included studies were divided into four key themes: (a) alterations in nocturnal urine regulation (n=6), (b) studies explicitly defining nocturia as ≥2 voids per main sleep period (n=3), (c) studies with subgroup data extracted according to nocturnal voiding frequency (n=5), (d) and studies examining circadian variations in bladder emptying efficiency (n=1). Findings across the included studies consistently demonstrated significant disruptions in circadian regulation among individuals experiencing nocturia (defined as ≥2 voids per main sleep period), compared to control groups or expected physiological patterns. Specifically, nocturnal secretion of melatonin and vasopressin was frequently reduced, while levels of natriuretic peptides were elevated, accompanied by diminished nocturnal blood pressure dipping. The reviewed studies examined diverse populations, including older adults, patients with obstructive sleep apnea, and individuals with spinal cord injury. Despite clinical heterogeneity, similar circadian alterations were observed across the different groups, particularly in relation to nighttime urine production and renal handling of solutes. Studies that stratified participants by nocturnal voiding frequency further supported these findings. Participants with ≥2 voids per main sleep period consistently showed increased nocturnal urine volume, altered fluid regulation, and reduced bladder capacity relative to those with fewer or no voids. Interpretation of results The results suggest a meaningful association between circadian rhythm disturbances and both the occurrence and severity of nocturia and nocturnal polyuria. Lower nighttime secretion of melatonin and vasopressin, together with elevated natriuretic peptides, may reflect compromised hormonal regulation contributing to increased nighttime urine production. A reduction in nocturnal blood pressure dipping could also indicate broader autonomic circadian dysfunction. These patterns highlight the complex and multifactorial nature of nocturia and support the idea that circadian dysregulation may represent a relevant therapeutic target. However, heterogeneity in study design and outcome measures requires cautious interpretation and underscores the need for standardized, prospective research. Concluding message This systematic review provides consistent evidence that circadian rhythm disturbances contribute to nocturia and nocturnal polyuria. Understanding this link may help refine clinical assessment and support the use of circadian-focused treatment in patients who do not respond to conventional therapies. Further research using standardized methods and objective circadian markers is needed to better define their role in symptom development and treatment response. Download: Download high-res image (140KB) Download: Download full-size image Figure 1 . PRISMA 2020 flow diagram Funding none Clinical Trial No Subjects Human Ethics not Req'd It is a systematic review. Helsinki not Req'd It is a systematic review. Informed Consent No

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