Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications (“Sleep C.A.L.M.”) in the evaluation and management of nocturia: A simple approach to a complex diagnosis

Abstract

Introduction Nocturia arises from a fundamental mismatch between nocturnal urine production, storage capacity, and sleep architecture, which may be driven by abnormalities of the genitourinary tract, but also by sleep disorders, medical diseases, patient actions/lifestyle factors, or medications. This article introduces a novel system for organizing the complex differential diagnosis for nocturia, as proposed by an international collective of practicing urologists, physician specialists, and sleep experts: “Sleep CALM”—Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications. Methods Narrative review of current evidence regarding the relevance of each “Sleep CALM” factor to nocturia pathogenesis, evaluation, and management. Results Nocturia and sleep disorders are highly intertwined and often bidirectional, such that nocturnal awakenings for reasons other than a sensation of bladder fullness should not be used as grounds for exclusion from nocturia treatment, but rather leveraged to broaden therapeutic options for nocturia. Nocturia is an important potential harbinger of several serious medical conditions beyond the genitourinary tract. Urologists should have a low threshold for primary care and medical specialty referral for medical optimization, which carries the potential to significantly improve nocturnal voiding frequency in addition to overall health status. Adverse patient actions/lifestyle factors, lower urinary tract dysfunction, and medication use commonly coexist with disordered sleep and comorbid medical conditions, and may be the primary mediators of nocturia severity and treatment response, or further exacerbate nocturia severity and complicate treatment. Conclusion “Sleep CALM” provides a memorable and clinically relevant means by which to structure the initial patient history, physical exam, and clinical testing in accordance with current best‐practice guidelines for nocturia. Although not intended as an all‐encompassing diagnostic tool, the “Sleep CALM” schema may also be useful in guiding individualized ancillary testing, identifying the need for specialty referral and multidisciplinary care, and uncovering first‐line treatment targets.

Application of the Sleep C.A.L.M. Tool for Assessing Nocturia in a Large Nationally Representative Cohort

“…categories likely contribute to a large part of this association, as many relevant diagnoses and contributory factors which comprise the Sleep C.A.L.M. categories also increase in prevalence with age [ 5 ]. Interestingly, however, the strength of the association between nocturia and the presence and number of Sleep C.A.L.M.…”

“…As is inherent to the concept of Sleep C.A.L.M., nocturia may indeed exist in the absence of identifiable genitourinary abnormalities and associated LUTS, but nevertheless remains pervasive in the context of common urologic conditions—more common in men with prostatic obstruction compared to their contemporary counterparts, and present in up to 85% of participants in pivotal overactive bladder syndrome trials [ 21 ]. Just as several systemic conditions have been associated with nocturia, so too are many common medications used in their treatment, which may adversely promote excess nocturnal urine production, directly affect the bladder, or conceivably lower the threshold at which bladder afferent signaling is sufficient to overcome the mechanisms maintaining sleep via alterations in sleep architecture [ 5 ].…”

“…Unfortunately, the complex diagnostic conundrum of nocturia undoubtedly contributes to the fact that nocturia is often insufficiently evaluated and under-treated, with several shortcomings known to exist between current consensus guidelines and real-world practice [ 3 , 4 ]. Recently, a memorable structure was proposed to facilitate a comprehensive clinical evaluation of nocturia in accordance with current International Continence Society (ICS) guidelines, including 5 common underlying categories: Sleep disorders, Comorbidities, Actions (i.e., modifiable patient behaviors such as excess fluid intake), Lower urinary tract dysfunction, and Medications [ 5 ]. The so-called “Sleep C.A.L.M.” categories are thought to collectively reflect most underlying causes of nocturia, and thus must all be effectively diagnosed and triaged as part of initial nocturia management [ 6 ].…”

The role of renal circadian biorhythms in lifelong LUTS

“…This predisposition to excess urine production has significant implications for clinical evaluation. 30 A bladder diary is crucial to diagnose nocturnal polyuria, while a sleep diary aids in understanding sleep quality and nocturnal awakenings in older adults. 31 Comprehensive assessment should also explore potential comorbidities and medications contributing to nocturia, addressing overall health status.…”

Prevalence of Sleep CALM nocturia factors in a male veteran population

“…1,4 Recently, we proposed a helpful structure which organizes 5 of the most common conditions underlying nocturia: Sleep disorders, Comorbidities, Actions (i.e., modifiable patient behaviors such as excess fluid intake), Lower urinary tract dysfunction (LUTD), and Medications. 5 Collectively, the so-called "Sleep C.A.L.M." factors are thought to contribute to most cases of nocturia in the clinical urology setting, and are also notable in that each requires judicious evaluation as part of initial management of nocturia according to consensus guidelines.…”