Nocturia and Aging: Diagnosis and Treatment
2010; Elsevier BV; Volume: 17; Issue: 4 Linguagem: Inglês
10.1053/j.ackd.2010.04.004
ISSN1548-5609
AutoresSarinya Boongird, Nirav Shah, Thomas D. Nolin, Mark Unruh,
Tópico(s)Pharmacology and Obesity Treatment
ResumoNocturia is a frequently encountered problem in clinical practice and a reason for nephrology consultation. Many studies have clearly shown the negative effect of nocturia on several aspects of health-related quality of life and morbidity. Age-associated physiological, structural, hormonal, and histological changes play an important role in the increasing incidence of nocturia in elderly individuals. Besides urologic conditions, nocturia may also be the initial presenting symptom in chronic kidney disease, as well as other systemic diseases. Therefore, it is essential to understand the complex pathophysiology among these factors to establish a precise diagnosis and appropriate management strategies. This review will provide an overview of the effect of aging on the kidneys and urinary system, the pathophysiology, clinical assessment, and treatment strategies of nocturia, and its effect on health-related quality of life. Nocturia is a frequently encountered problem in clinical practice and a reason for nephrology consultation. Many studies have clearly shown the negative effect of nocturia on several aspects of health-related quality of life and morbidity. Age-associated physiological, structural, hormonal, and histological changes play an important role in the increasing incidence of nocturia in elderly individuals. Besides urologic conditions, nocturia may also be the initial presenting symptom in chronic kidney disease, as well as other systemic diseases. Therefore, it is essential to understand the complex pathophysiology among these factors to establish a precise diagnosis and appropriate management strategies. This review will provide an overview of the effect of aging on the kidneys and urinary system, the pathophysiology, clinical assessment, and treatment strategies of nocturia, and its effect on health-related quality of life. Nocturia has been defined as the need for an individual to wake up 1 or more times during the night to void.1van Kerrebroeck P. Abrams P. Chaikin D. et al.The standardisation of terminology in nocturia: Report from the Standardisation Sub-committee of the International Continence Society.Neurourol Urodyn. 2002; 21: 179-183Crossref PubMed Scopus (496) Google Scholar The prevalence of nocturia varies markedly, depending on the definition and age group surveyed. Nevertheless, one common finding is that the prevalence of nocturia increases with age, ranging from 4% in children aged 7 to 15 years to approximately 70% in adults aged >60 years.2Mattsson S. Urinary incontinence and nocturia in healthy schoolchildren.Acta Paediatr. 1994; 83: 950-954Crossref PubMed Scopus (78) Google Scholar, 3Irwin D.E. Milsom I. Hunskaar S. et al.Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: Results of the EPIC study.Eur Urol. 2006; 50 (discussion 1314–1315): 1306-1314Abstract Full Text Full Text PDF PubMed Scopus (1719) Google Scholar Tikkinen and colleagues4Tikkinen K.A. Tammela T.L. Huhtala H. et al.Is nocturia equally common among men and women? A population based study in Finland.J Urol. 2006; 175: 596-600Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar assessed the occurrence of nocturia in 6000 subjects aged 18 to 79 years and found that the prevalence increased with age, but the estimates depended on whether nocturia was defined as 1 or 2 voids per night. In this report, in men and women aged 70 years the prevalence of at least 2 voids per evening was 40%.4Tikkinen K.A. Tammela T.L. Huhtala H. et al.Is nocturia equally common among men and women? A population based study in Finland.J Urol. 2006; 175: 596-600Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar The actual prevalence, however, may be even higher than previously reported, as some patients consider it as normal or part of normal aging, and do not seek help from healthcare professionals. The clinical significance and the "degree of bother" have been explored by Tikkenen and colleagues who noted that the degree of bother and health-related quality of life (HRQoL) correlates with the number of voids. However, not all bother is correlated to episodes of nocturia. This suggests that bother may also be related to comorbidities that can affect HRQoL.45Tikkinen K.A. Johnson 2nd, T.M. Tammela T.L. et al.Nocturia frequency, bother, and quality of life: How often is too often? A population-based study in Finland.Eur Urol. 2010; 57: 488-496Abstract Full Text Full Text PDF PubMed Scopus (234) Google Scholar The clinical significance of nocturia is more important than the number of episodes of nocturia. Although the prevalence of nocturia does increase with age, it would be difficult to conclude that nocturia is a normal part of aging because it is not universally present in all older adults. Many of the physiological, structural, and hormonal risk factors for nocturia are known to increase with age. The clinical significance of nocturia has been difficult to quantify but has been increasingly recognized because of associations with reduced HRQoL, and increased morbidity and mortality.6Coyne K.S. Zhou Z. Bhattacharyya S.K. et al.The prevalence of nocturia and its effect on health-related quality of life and sleep in a community sample in the USA.BJU Int. 2003; 92: 948-954Crossref PubMed Scopus (255) Google Scholar, 7Asplund R. Mortality in the elderly in relation to nocturnal micturition.BJU Int. 1999; 84: 297-301Crossref PubMed Scopus (175) Google Scholar, 8Kobelt G. Health-economic issues in nocturia.BJU Int. 1999; 84: 29-32PubMed Google Scholar, 9Guilleminault C. Lin C.M. Goncalves M.A. et al.A prospective study of nocturia and the quality of life of elderly patients with obstructive sleep apnea or sleep onset insomnia.J Psychosom Res. 2004; 56: 511-515Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar Recently, Agarwal and colleagues have noted associations of nocturia with non-dipping and effects on hypertension (HTN).10Agarwal R. Light R.P. Bills J.E. et al.Nocturia, nocturnal activity, and nondipping.Hypertension. 2009; 54: 646-651Crossref PubMed Scopus (60) Google Scholar The causes of nocturia are varied, involving both urologic and nonurologic conditions influenced by the aging process. There is an increasing role for nephrologists in managing nocturia in collaboration with urologists and primary care physicians because it affects HRQoL and may also be the initial presenting symptom in chronic kidney disease (CKD), as well as other systemic diseases, such as congestive heart failure (CHF), diabetes mellitus (DM), or sleep disorders. This review helps examine the roles of aging and kidneys in promoting nocturia as well as nonpharmacologic and pharmacologic therapies for the treatment of nocturia. Age-associated physiological, structural, hormonal, and histologic changes play an important role in the increasing incidence of nocturia in the elderly population. Mismatch between amounts of urine produced at night and the bladder's capacity to hold adequate urine volumes during sleep accounts for a common mechanism of nocturia. With aging, several factors which determine kidney sodium handling, water conserving mechanism, and circadian rhythm of glomerular filtration rate (GFR) have been altered in the direction of promoting nocturnal diuresis. The concentrating ability of the kidney has been shown to decline with increasing age owing to impaired responsiveness to arginine vasopressin (AVP).5Ouslander J.G. Nasr S.Z. Miller M. et al.Arginine vasopressin levels in nursing home residents with nighttime urinary incontinence.J Am Geriatr Soc. 1998; 46: 1274-1279PubMed Google Scholar, 11Tian Y. Serino R. Verbalis J.G. Downregulation of renal vasopressin V2 receptor and aquaporin-2 expression parallels age-associated defects in urine concentration.Am J Physiol Renal Physiol. 2004; 287: F797-F805Crossref PubMed Scopus (36) Google Scholar In young healthy adult, AVP normally has a circadian pattern of release in which its blood concentration peaks during the night, resulting in nocturnal urine production falling to approximately 25% or less of total daily urine output.12Kikuchi Y. Participation of atrial natriuretic peptide (hANP) levels and arginine vasopressin (AVP) in aged persons with nocturia [in Japanese].Nippon Hinyokika Gakkai Zasshi. 1995; 86: 1651-1659PubMed Google Scholar However, in elderly individuals, the AVP response to volume and osmotic stimuli remains intact, but circadian nocturnal AVP secretion is disrupted.5Ouslander J.G. Nasr S.Z. Miller M. et al.Arginine vasopressin levels in nursing home residents with nighttime urinary incontinence.J Am Geriatr Soc. 1998; 46: 1274-1279PubMed Google Scholar, 12Kikuchi Y. Participation of atrial natriuretic peptide (hANP) levels and arginine vasopressin (AVP) in aged persons with nocturia [in Japanese].Nippon Hinyokika Gakkai Zasshi. 1995; 86: 1651-1659PubMed Google Scholar, 13Ohashi M. Fujio N. Nawata H. High plasma concentrations of human atrial natriuretic polypeptide in aged men.J Clin Endocrinol Metab. 1987; 64: 81-85Crossref PubMed Scopus (148) Google Scholar, 14Koopman M.G. Koomen G.C. Krediet R.T. et al.Circadian rhythm of glomerular filtration rate in normal individuals.Clin Sci (Lond). 1989; 77: 105-111PubMed Google Scholar This results in a shift of the diurnal rhythm of urine production toward increasing nighttime urine excretion. Additionally, Asplund and Aberg demonstrated that dysregulation of AVP secretion is only partly responsible for nocturnal polyuria among elderly patients.15Asplund R. Aberg H. Diurnal variation in the levels of antidiuretic hormone in the elderly.J Intern Med. 1991; 229: 131-134Crossref PubMed Scopus (182) Google Scholar It has been observed by some investigators that attenuation of the decrement of GFR during sleep may also contribute to increased nocturnal urine production and urinary sodium excretion rates in the elderly population.11Tian Y. Serino R. Verbalis J.G. Downregulation of renal vasopressin V2 receptor and aquaporin-2 expression parallels age-associated defects in urine concentration.Am J Physiol Renal Physiol. 2004; 287: F797-F805Crossref PubMed Scopus (36) Google Scholar, 12Kikuchi Y. Participation of atrial natriuretic peptide (hANP) levels and arginine vasopressin (AVP) in aged persons with nocturia [in Japanese].Nippon Hinyokika Gakkai Zasshi. 1995; 86: 1651-1659PubMed Google Scholar Besides age-related changes in kidney, there are multiple alterations in the hormonal systems governing water and sodium regulation that can occur with aging. Atrial natriuretic peptide (ANP) is an important factor in controlling sodium excretion through its direct natriuretic effect, and suppression of renal renin and aldosterone secretion. With advanced age, the basal ANP level has been shown to be 3- to 5-fold higher than those of young adults.5Ouslander J.G. Nasr S.Z. Miller M. et al.Arginine vasopressin levels in nursing home residents with nighttime urinary incontinence.J Am Geriatr Soc. 1998; 46: 1274-1279PubMed Google Scholar, 15Asplund R. Aberg H. Diurnal variation in the levels of antidiuretic hormone in the elderly.J Intern Med. 1991; 229: 131-134Crossref PubMed Scopus (182) Google Scholar Moreover, plasma renin and aldosterone activities are also decreased with aging. As a consequence, the aforementioned hormonal changes promote natriuresis and result in diuresis. Age-related decrements in both functional and structural capacity impair the bladder's ability to store urine overnight. It has been shown that nocturnal bladder capacity and detrusor contractility diminish with age because of an increased collagen to smooth muscle ratio.12Kikuchi Y. Participation of atrial natriuretic peptide (hANP) levels and arginine vasopressin (AVP) in aged persons with nocturia [in Japanese].Nippon Hinyokika Gakkai Zasshi. 1995; 86: 1651-1659PubMed Google Scholar, 16Kawauchi A. Tanaka Y. Soh J. et al.Causes of nocturnal urinary frequency and reasons for its increase with age in healthy older men.J Urol. 2000; 163: 81-84Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 17Susset J.G. Servot-Viguier D. Lamy F. et al.Collagen in 155 human bladders.Invest Urol. 1978; 16: 204-206PubMed Google Scholar Ouslander has outlined the current understanding of sensory innervation of the bladder and highlighted potential targets for therapeutic advances.18Ouslander J.G. Management of overactive bladder.N Engl J Med. 2004; 350: 786-799Crossref PubMed Scopus (351) Google Scholar Although nocturia in elderly men with other lower urinary tract symptoms is frequently attributed to bladder outlet obstruction caused by benign prostatic hyperplasia (BPH), other urologic conditions that cause reduction in bladder capacity, such as bladder irritation from stone or infection, and urogenital neoplasm should also be considered and investigated as well. In women, age-associated structural and hormonal changes may be significant contributing factors. Estrogen deficiency in postmenopausal women results in structural and physiologic changes, including urogenital atrophy, pelvic organ prolapse, pelvic floor relaxation, and neurogenic detrusor hyperactivity. Consequently, these alterations cause irritative symptoms and nocturia.19Pandit L. Ouslander J.G. Postmenopausal vaginal atrophy and atrophic vaginitis.Am J Med Sci. 1997; 314: 228-231Crossref PubMed Scopus (154) Google Scholar Nocturia is an early and common manifestation and has been reported as one of the most prevalent and severe symptoms among patients with CKD.21Agarwal R. Developing a self-administered CKD symptom assessment instrument.Nephrol Dial Transplant. 2010; 25: 160-166Crossref PubMed Scopus (20) Google Scholar There are several factors accounting for nocturia in CKD. The widely described hypothesis is the inability to concentrate urine because of the diminished ability of the medullary interstitium to generate and maintain a countercurrent system, and decreased responsiveness of cortical collecting duct to AVP, resulting in a relative water diuresis.22Conte G. Dal Canton A. Fuiano G. et al.Mechanism of impaired urinary concentration in chronic primary glomerulonephritis.Kidney Int. 1985; 27: 792-798Crossref PubMed Scopus (12) Google Scholar However, recent work has shown that osmotic diuresis and not water diuresis is responsible for the main mechanism of nocturia in CKD.23Feinfeld D.A. Danovitch G.M. Factors affecting urine volume in chronic renal failure.Am J Kidney Dis. 1987; 10: 231-235PubMed Scopus (20) Google Scholar, 24Fukuda M. Motokawa M. Miyagi S. et al.Polynocturia in chronic kidney disease is related to natriuresis rather than to water diuresis.Nephrol Dial Transplant. 2006; 21: 2172-2177Crossref PubMed Scopus (32) Google Scholar The major osmotic component and the mechanism of increased nocturnal solute excretion, however, are still inconclusive. Fukuda and colleagues24Fukuda M. Motokawa M. Miyagi S. et al.Polynocturia in chronic kidney disease is related to natriuresis rather than to water diuresis.Nephrol Dial Transplant. 2006; 21: 2172-2177Crossref PubMed Scopus (32) Google Scholar measured urinary sodium, potassium, urea excretion, and osmolar excretion rates, as well as free-water clearance, and correlated the values obtained with urinary volume during daytime and nighttime in CKD patients. It was reported that nocturnal urine volume in CKD patients was determined principally by natriuresis and not by water diuresis or urea excretion. Interestingly, the enhanced natriuresis has been found to be associated with a lack of nocturnal blood pressure fall, a common phenomenon in CKD patients known as nondipping.10Agarwal R. Light R.P. Bills J.E. et al.Nocturia, nocturnal activity, and nondipping.Hypertension. 2009; 54: 646-651Crossref PubMed Scopus (60) Google Scholar, 24Fukuda M. Motokawa M. Miyagi S. et al.Polynocturia in chronic kidney disease is related to natriuresis rather than to water diuresis.Nephrol Dial Transplant. 2006; 21: 2172-2177Crossref PubMed Scopus (32) Google Scholar Recently, Agarwal and colleagues demonstrated that increased nighttime physical activity contributed to nondipping blood pressure patterns in CKD patients, presumably mediated by frequent nocturia.10Agarwal R. Light R.P. Bills J.E. et al.Nocturia, nocturnal activity, and nondipping.Hypertension. 2009; 54: 646-651Crossref PubMed Scopus (60) Google Scholar Nevertheless, the relationship between nondipping and nocturia remains unclear, thus stressing the need for further studies to be carried out. Some authors propose that nocturia may be another marker indicating progression of kidney injury that should prompt primary care physicians to consider screening for CKD when evaluating patients with nocturia, and vice versa.20Krol E. Rutkowski B. Czarniak P. et al.Early detection of chronic kidney disease: Results of the PolNef study.Am J Nephrol. 2009; 29: 264-273Crossref PubMed Scopus (53) Google Scholar, 25Hsu C.Y. Iribarren C. McCulloch C.E. et al.Risk factors for end-stage renal disease: 25-year follow-up.Arch Intern Med. 2009; 169: 342-350Crossref PubMed Scopus (395) Google Scholar Alternatively, Agarwal studied 98 patients with CKD (eGFR <60) and failed to demonstrate a trend toward increased severity of nocturia with worsening renal function. The multiple etiologies of CKD may explain the variable presentation of nocturia.21Agarwal R. Developing a self-administered CKD symptom assessment instrument.Nephrol Dial Transplant. 2010; 25: 160-166Crossref PubMed Scopus (20) Google Scholar The pathogenesis of nocturia is complex and sometimes multifactorial, involving several organ systems. Furthermore, some conditions or diseases are complicated by environmental, behavioral, and pathologic factors. The mechanism responsible for nocturia includes any conditions resulting in abnormally increased urine production, decreased bladder storage capacity, or disturbed sleep pattern leading to waking at night. Looking into the mechanism of nocturia involved in different disease states gives further insight into the complex multifaceted pathophysiology. For example, although the mechanism between nocturia and HTN is not fully explained, McKeigue's work showed that HTN and nocturia may share similar pathophysiology with alterations in nitric oxide metabolism and resetting of the pressure natriuresis balance in the kidney leading to sodium retention and compensatory nocturnal natriuresis.26McKeigue P.M. Reynard J.M. Relation of nocturnal polyuria of the elderly to essential hypertension.Lancet. 2000; 355: 486-488Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar Diurnal polyuria is defined as having a urine production of more than 40 mL/kg of body weight over a 24-hour period. It may result from either free water diuresis (eg, diabetes insipidus [DI] or excessive fluid intake) or osmotic diuresis (eg, poorly controlled diabetes mellitus). Central DI is characterized by decreased production of AVP, whereas nephrogenic DI results from a decrease in the ability of the kidneys to concentrate urine because of an impaired renal tubular response to AVP. In addition, diurnal polyuria may be because of either primary polydipsia or excessive fluid intake, which is distinguished from DI by water deprivation test. In patients with edema-forming states, such as CHF and CKD, fluid and solute accumulated in the lower extremities while standing during the day may become mobilized into the circulatory systems at night, inducing ANP release. Enhanced ANP secretion because of medical conditions can also cause nocturnal polyuria. ANP is released by atrial myocytes in response to atrial distension and sympathetic stimulation. It affects the kidneys by increasing GFR and filtration fraction, which in turn produces natriuresis and diuresis. Similarly, respiratory diseases associated with increased airway resistance, such as obstructive sleep apnea (OSA), stimulate ANP secretion through hypoxic-induced vasoconstriction causing increased right atrial pressure.27Yalkut D. Lee L.Y. Grider J. et al.Mechanism of atrial natriuretic peptide release with increased inspiratory resistance.J Lab Clin Med. 1996; 128: 322-328Abstract Full Text PDF PubMed Scopus (39) Google Scholar Studies have shown the increase in frequency of nocturia in OSA patients as well as positive correlation between severity of OSA and frequency of nocturnal urination.28Kaynak H. Kaynak D. Oztura I. Does frequency of nocturnal urination reflect the severity of sleep-disordered breathing?.J Sleep Res. 2004; 13: 173-176Crossref PubMed Scopus (55) Google Scholar Finally, some behavioral habits can lead to nocturnal polyuria, for example, consuming diuretic in late-evening, or ingestion of fluid or beverages with diuretic-like properties (ie, caffeine, alcohol) shortly before bedtime. Diminished bladder capacity refers to a condition in which voiding occurs at bladder volumes less than functional bladder capacity, leading to awakening to void at night. Reduction in bladder capacity can occur at all times (reduced global bladder capacity), or exclusively at night (reduced nocturnal bladder capacity). Diminished global capacity is often related to urologic conditions, including bladder outlet obstruction resulting in increased postvoid residual urine volume (PVR), bladder irritation from stones, infection or neoplasm, extrinsic bladder compression from ovarian cancer or uterine fibroids, and decreased bladder capacity because of urogenital aging. BPH and overactive bladder (OAB) are 2 main urologic conditions associated with diminished bladder capacity. Traditionally, nocturia in men has been attributed to bladder outlet obstruction relating to BPH. Diminished bladder capacity in BPH is explained by increased PVR and detrusor hyperactivity induced by chronic bladder outlet obstruction. OAB is defined by the International Continence Society as a syndrome of urinary urgency, with or without urge incontinence, usually accompanied by increased frequency and nocturia.29Abrams P. Cardozo L. Fall M. et al.The standardisation of terminology of lower urinary tract function: Report from the Standardisation Sub-committee of the International Continence Society.Neurourol Urodyn. 2002; 21: 167-178Crossref PubMed Scopus (5202) Google Scholar OAB symptoms are often attributed to detrusor overactivity, which is corroborated by urodynamic testing. Common causes of overactive bladder are listed in Table 1. In patients with signs of bladder storage problems, urodynamic studies are often required to confirm and determine the classification of these disorders.Table 1Etiologies of Nocturia and Associated ConditionsDiurnal polyuria Water diuresis:Primary polydipsia: psychogenic or dipsogenic polydipsiaDiabetes insipidus: defect in secretion or action of AVP Central diabetes insipidus (eg, hypothalamic or pituitary lesion) Nephrogenic diabetes insipidus (eg, medications, hypercalcemia, hypokalemia, hereditary disorders) Gestational diabetes insipidus Osmotic diuresisPoorly controlled diabetes mellitusMedications (eg, mannitol, sorbitol)Nocturnal polyuria Nocturnal polyuria syndrome Edema-forming states (eg, CHF, CKD, nephrotic syndrome, hypoalbuminemia, chronic liver disease, venous insufficiency) Behavioral factors (eg, excessive fluid intake shortly before retiring, late-evening diuretic intake) Comorbidities (eg, obstructive sleep apnea, Alzheimer's disease, multisystem atrophy, stroke, Parkinsonism)Diminished bladder capacity Overactive bladder syndrome (eg, detrusor overactivity, detrusor underactivity, neurologic conditions causing alteration of efferent and afferent neural voiding pathways) Reduced bladder capacity (eg, bladder cancer, BPH, bladder fibrosis, neurogenic bladder) Others (eg, infection, stones, tumor, pelvic floor laxity, medication)Sleep disturbances Sleep apnea syndrome Periodic limb movement disorderAbbreviations: AVP, arginine vasopressin; CHF, congestive heart failure; CKD, chronic kidney disease; BPH, benign prostatic hyperplasia. Open table in a new tab Abbreviations: AVP, arginine vasopressin; CHF, congestive heart failure; CKD, chronic kidney disease; BPH, benign prostatic hyperplasia. Some studies have suggested that 2 or more voids per night are clinically significant and correlate with degree of bother.45Tikkinen K.A. Johnson 2nd, T.M. Tammela T.L. et al.Nocturia frequency, bother, and quality of life: How often is too often? A population-based study in Finland.Eur Urol. 2010; 57: 488-496Abstract Full Text Full Text PDF PubMed Scopus (234) Google Scholar In addition, the consequence or adverse effects of nocturia are important to be noted. For example, nocturia has been associated with reduced daytime performance, low productivity at work, absenteeism, and depression.4Tikkinen K.A. Tammela T.L. Huhtala H. et al.Is nocturia equally common among men and women? A population based study in Finland.J Urol. 2006; 175: 596-600Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar Short and fragmented sleep has been linked with an increased risk of cardiovascular disease, traumatic injury, and possibly mortality.4Tikkinen K.A. Tammela T.L. Huhtala H. et al.Is nocturia equally common among men and women? A population based study in Finland.J Urol. 2006; 175: 596-600Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar, 7Asplund R. Mortality in the elderly in relation to nocturnal micturition.BJU Int. 1999; 84: 297-301Crossref PubMed Scopus (175) Google Scholar Nocturia not only imposes a burden on HRQoL in the individual, but also on others, as interruption of sleep to void can result in frequent awakenings and difficulty falling asleep in their partners or caregivers and may even influence the decision to institutionalize the elderly people.30Kaye M. Aging, circadian weight change, and nocturia.Nephron Physiol. 2008; 109: 11-18Crossref Scopus (7) Google Scholar, 31Cugini P. Lucia P. Di Palma L. et al.Effect of aging on circadian rhythm of atrial natriuretic peptide, plasma renin activity, and plasma aldosterone.J Gerontol. 1992; 47: B214-B219Crossref PubMed Scopus (28) Google Scholar, 41Pollak C.P. Perlick D. Sleep problems and institutionalization of the elderly.J Geriatr Psychiatry Neurol. 1991; 4: 204-210Crossref PubMed Scopus (302) Google Scholar The consequences of nocturia are profound and explain the heightened interest into understanding the epidemiology, pathophysiology, and explore any possible treatment options. There are several nocturia-specific HRQoL questionnaires or instruments available to physicians such as the International Consultation on Incontinence Modular Questionnaire-Nocturia Quality of life, and the Nocturia, Nocturnal Enuresis, and Sleep-interruption Questionnaire.32Mock L.L. Parmelee P.A. Kutner N. et al.Content validation of symptom-specific nocturia quality-of-life instrument developed in men: Issues expressed by women, as well as men.Urology. 2008; 72: 736-742Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 33Abraham L. Hareendran A. Mills I.W. et al.Development and validation of a quality-of-life measure for men with nocturia.Urology. 2004; 63: 481-486Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar, 34Bing M.H. Moller L.A. Jennum P. et al.Validity and reliability of a questionnaire for evaluating nocturia, nocturnal enuresis and sleep-interruptions in an elderly population.Eur Urol. 2006; 49: 710-719Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar In addition, sleep questionnaires such as the Pittsburgh Sleep Quality Index assess nocturnal voiding as a single item.35Buysse D.J. Reynolds 3rd, C.F. Monk T.H. et al.The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research.Psychiatry Res. 1989; 28: 193-213Abstract Full Text PDF PubMed Scopus (14967) Google Scholar To our knowledge, there are no universally accepted definitions to determine the frequency of nocturia per night that would be clinically meaningful. Some authors suggested that ≥2 voids per night are bothersome and clinically significant.6Coyne K.S. Zhou Z. Bhattacharyya S.K. et al.The prevalence of nocturia and its effect on health-related quality of life and sleep in a community sample in the USA.BJU Int. 2003; 92: 948-954Crossref PubMed Scopus (255) Google Scholar, 36Schatzl G. Temml C. Schmidbauer J. et al.Cross-sectional study of nocturia in both sexes: Analysis of a voluntary health screening project.Urology. 2000; 56: 71-75Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar, 45Tikkinen K.A. Johnson 2nd, T.M. Tammela T.L. et al.Nocturia frequency, bother, and quality of life: How often is too often? A population-based study in Finland.Eur Urol. 2010; 57: 488-496Abstract Full Text Full Text PDF PubMed Scopus (234) Google Scholar In the clinical setting, it would be important to assess both how frequently the patient wakes to void and to what extent the nocturia bothers the patient. The degree of bother and clinical significance of nocturia is important to help guide the health care provider in providing therapy that may also involve its own risks. Nocturia has been shown to be associated with poor sleep quality and several types of sleep disorders, including obstructive and central apnea syndrome, periodic limb movement disorder, and sleep disorders related to medical or neurologic diseases. Nocturia is an independent predictor for self-reported insomnia and sleep fragmentation.37Bliwise D.L. Foley D.J. 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