Prevalence of the nocturnal polyuria syndrome in men.

AIMS: Nocturnal polyuria (NP) is caused by a wide array of factors, including genitourinary and systemic comorbidities, modifiable behavior, and pharmaceuticals. When an identifying factor is absent, NP may be purely a symptom of the nocturnal polyuria syndrome (NPS) and secondary to blunting of normal arginine vasopressin action within the circadian rhythm. The purpose of this study is to determine the prevalence of NPS in male patients attending a Veterans Affairs outpatient urology clinic. METHODS: Retrospective database analysis was performed of voiding diaries from men who had established care for lower urinary tract symptoms from 2007 to 2018. Patients were excluded if they reported fewer than two nocturnal voids on voiding diary analysis or had comorbidity associated with NP. Distinct cutoffs were separately employed to identify NP: nocturnal polyuria index (NPi; calculated as nocturnal urine volume divided by 24-hour urine volume) greater than 0.33; and nocturnal urine production (NUP) greater than 90 mL/h. RESULTS: A total of 283 completed voiding diaries were evaluated and 202 patients had ≥2 nocturnal voids. After exclusions, at NPi greater than 33, the floor and ceiling NPS prevalence values were 21% and 41%, respectively. At NUP greater than 90 mL/h, the floor and ceiling NPS prevalence values were 17% and 32%, respectively. CONCLUSIONS: The prevalence of NPS in patients with nocturia in the present study lies between 17% and 41%. NPS constitutes a clinically relevant subgroup of nocturia among male patients in the Veterans Affairs outpatient urology setting.

Correction to: Association between nocturia and frailty among elderly males in a veterans administration population.

In the original publication of the article, the author's name Jeffrey P. Weiss was misspelled as "Jeffry P. Weiss".

Phenotyping nocturnal polyuria: circadian and age-related variations in diuresis rate, free water clearance and sodium clearance.

BACKGROUND: this study compares diuresis rate, sodium clearance and free water clearance (FWC) by age and time of day (nighttime vs. daytime) in subjects with and without nocturnal polyuria (NP) to determine whether these variables affect the phenotype of NP. METHODS: post hoc analysis of two prospective observational studies. Eight urine samples collected at 3-h intervals and a single blood sample were used to calculate daytime (10a/1p/4p/7p/10p) and nighttime (1a/4a/7a) diuresis rates, sodium clearance and FWC. Three mixed linear models were constructed for diuresis rate, sodium clearance and FWC using four predictor variables: NP status (present [nocturnal urine production >90 ml/h] vs. absent [≤90 ml/h]), time of day, age and study identification. RESULTS: subjects with NP experienced higher nighttime versus daytime diuresis rates, sodium clearance and FWC. Regardless of NP status, increased age was accompanied by an increase in the ratio of nighttime/daytime diuresis rate, nighttime sodium clearance and daytime sodium clearance. FWC showed a complex age effect, which was independent of time of day or NP status. CONCLUSIONS: age-related increases in nighttime/daytime diuresis rate, 24-h sodium clearance and 24-h FWC are not specific to subjects with NP. The age-related surge in either nocturnal sodium clearance or nocturnal FWC may represent the relevant substrate for behavioural or pharmacologic interventions targeting sodium diuresis or free water diuresis, respectively. Increases in FWC in older age groups may reflect impaired circadian rhythmicity of endogenous AVP or changes in responsiveness of the aged nephron to water clearance.

Sodium restriction improves nocturia in patients at a cardiology clinic.

This study aims to determine whether dietary sodium restriction counseling decreases nocturnal voiding frequency in cardiology patients with concomitant nocturia. Patients who had established care at a cardiology clinic from 2015 to 2018 reporting ≥1 average nocturnal void(s) underwent a comprehensive sodium intake interview by their cardiologist, who provided them with individualized strategies for dietary sodium reduction and assessed adherence at follow-up. Average nocturnal voiding frequency and dietary adherence were documented in the medical record. A nocturia database was compiled for retrospective analysis. A total of 74 patients were included. Patients considered to be adherent with dietary sodium restriction at follow-up (n = 56) demonstrated a decrease in median nocturia frequency (2.5 [2.3-3.0] vs 1.0 [1.0-2.0] voids, P < .001). Among nonadherent patients (n = 18), median nocturia frequency did not significantly change from baseline to follow-up (2.0 [1.5-3.8] vs 2.0 [1.5-4.8] voids, P = .423). Median changes were significantly different between the adherent and nonadherent groups (P < .001). Examination of second follow-up available from 37 patients showed a continued effect. In conclusion, adherence with dietary sodium counseling appears to improve nocturia. Accordingly, dietary modification may represent an important adjunct therapy to lifestyle and pharmacologic interventions for decreasing nocturia frequency. Reduction in nocturnal voiding frequency may also reflect an additional benefit of dietary sodium restriction in accordance with best practice standards for cardiovascular disease.

Time of peak nocturnal diuresis rate between men with secondary nocturnal polyuria versus nocturnal polyuria syndrome.

AIM: Compare the circadian trajectory of diuresis between nocturnal polyuria (NP) patients with versus without identifiable contributory comorbidities. METHODS: Retrospective analysis of frequency-volume charts from male patients with clinically-significant nocturia (≥2 nocturnal voids) and NP (defined by nocturnal urine production [NUP] ≥90 mL/hour or nocturnal polyuria index [NPi] ≥0.33). Patients with NP and chronic kidney disease, congestive heart failure, and/or undertreated obstructive sleep apnea (OSA) were deemed to have secondary NP. Nocturnal polyuria syndrome (NPS) was defined as NP without edema, loop diuretic use, or the aforementioned conditions. Patients with diabetes insipidus or OSA with appropriate continuous positive airway pressure utilization were excluded. The timing and volumes of nocturnal voids were used to derive "early" and "late" nocturnal diuresis rates (mL/hour of urine produced before and after the first nocturnal awakening, respectively). The likelihood of an early peak nocturnal diuresis rate (ie, early >late nocturnal diuresis rate) was compared between patients with NPS versus secondary NP using both a crude and adjusted odds ratio. RESULTS: The likelihood of an early peak nocturnal diuresis rate in patients with NPS compared with secondary NP was 2.58 (1.05-6.31) at NUP ≥ 90 mL/hour and 1.96 (0.87-4.42) at NPi ≥ 0.33 on crude analysis, and 2.44 (0.96-6.24) and 1.93 (0.83-4.48) after adjustment, respectively. CONCLUSIONS: A peak early nocturnal diuresis rate was significantly more likely in patients with NPS at NUP ≥ 90 mL/hour, with similar odds ratios at NPi ≥ 0.33 and following adjustment. Delineating nocturic patients by NP subgroup may facilitate more individualized management. PATIENT SUMMARY: Many people have to wake up to urinate because they produce too much urine at night-a condition known as "nocturnal polyuria." Nocturnal polyuria might be caused by drinking too much fluid, other behavioral factors, or conditions that make your body hold on to too much fluid, like heart disease, kidney disease, and sleep apnea. In cases of nocturnal polyuria where no clear cause can be identified, it is thought that patients may suffer from a deficiency in nighttime vasopressin, a hormone that plays a key role in how much urine you produce. In this study, we compared the pattern of nighttime urine production in patients with different causes of nocturnal polyuria, which may lead to more personalized treatment options for patients with this condition.

Differential Nocturnal Diuresis Rates Among Patients with and Without Nocturnal Polyuria Syndrome.

BACKGROUND: The mechanism of nocturnal polyuria (NP), a leading cause of nocturia, is poorly understood. OBJECTIVE: To characterize NP in terms of diuresis rate changes before and after the first nocturnal awakening. DESIGN, SETTING, AND PARTICIPANTS: A frequency-volume chart (FVC) database of 773 entries from 440 veterans treated at a Veterans Affairs urology clinic was analyzed. The first FVCs completed by male patients aged ≥18 years with two or more nocturnal voids were included. Patients were excluded if they were taking diuretics or had sleep apnea, heart failure, edema, kidney disease, or diabetes insipidus. The 130 included individuals were divided into two cohorts: patients with NP and patients below this threshold. Analyses were performed using two different cutoffs for NP: nocturnal urine production (NUP) >90ml/h and nocturnal polyuria index (NPi) >0.33. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We compared "early nocturnal diuresis rate" (ENDR; first nocturnal voided volume/length of first uninterrupted sleep period), "late nocturnal diuresis rate" (LNDR; remaining nocturnal urine volume/remaining hours of sleep), and diurnal diuresis rate (daytime urine volume/hours awake) in patients with the nocturnal polyuria syndrome (NPS). RESULTS AND LIMITATIONS: Within groups, there were significant differences between ENDR and LNDR for NPS patients at NUP >90ml/h (152 vs 120ml/h, p=0.02) and NPi >0.33 (120 vs 91ml/h, p=0.02) but not for those without NPS at NUP ≤90ml/h (60 vs 59ml/h, p=0.29) or NPi ≤0.33 (75 vs 75ml/h, p=0.25). Limitations include retrospective design, single institution participation, and small sample size. CONCLUSIONS: There exists a significant drop-off in nocturnal diuresis rate after the time of first awakening that is unique to patients with NPS. The large volume of urine produced in the early hours of sleep may provide the specific substrate for short-acting antidiuretics approved for use in patients with nocturia owing to NPS. PATIENT SUMMARY: We analyzed adult males diagnosed with nocturnal polyuria syndrome to determine how their rate of urine production changed throughout the night. Our finding that these individuals produce urine at the highest rate in the early hours of sleep suggests that they may benefit from pharmaceuticals specifically designed to reduce urine production during this period.

Association between nocturia and frailty among elderly males in a veterans administration population.

BACKGROUND: The relationship between frailty and nocturnal voiding is poorly understood. AIM: To characterize the association between frailty, as defined by a frailty index (FI) based upon the Canadian Study of Health and Aging (CSHA) criteria, and nocturia, defined by measures of nocturnal urine production. METHODS: Real-world retrospective analysis of voiding diaries from elderly males with lower urinary tract symptoms (LUTS) at an outpatient urology clinic. Males ≥ 65 years with ≥ 2 nocturnal voids were included. A modified FI was calculated from the LUTS database, which captured 39 variables from the original CSHA FI. Patients were divided into 3 groups by modified FI: low (≤ 0.077) (n = 59), intermediate (> 0.077 and < 0.179) (n = 58), and high (≥ 0.179) (n = 41). Diary parameters were compared using the Kruskal-Wallis test and pairwise comparisons with the Wilcoxon rank-sum test and Bonferroni adjustment. RESULTS: The high frailty group was characterized by higher nocturnal urine volume (NUV), maximum voided volume (MVV), nocturnal maximum voided volume (NMVV), and nocturnal urine production (NUP). The presence of comorbid diabetes mellitus did not explain this effect. CONCLUSION: Elderly males seeking treatment for LUTS with a high frailty burden are disproportionately affected by excess nocturnal urine production. Future research on the mechanistic relationship between urine production and functional impairment is warranted.

Future Considerations in Nocturia and Nocturnal Polyuria.

Nocturnal polyuria (NP), the most common etiology of nocturia, can be caused by various medical conditions, including cardiovascular disease, obstructive sleep apnea, renal tubular dysfunction, as well as medications (eg, diuretics) and/or behavioral patterns. NP in the absence of underlying medical conditions has been described as NP syndrome and is thought be the result of impaired circadian release of endogenous arginine vasopressin. Desmopressin, a synthetic arginine vasopressin analog, has been shown to be an effective replacement therapy in adults with nocturia due to NP. Further studies on the subset of patients with NP syndrome are warranted to maximize benefit from antidiuretic treatment. In addition, a connection between the pathophysiological mechanisms underlying NP and essential hypertension has been suggested, and hypertension has been shown to be a significant risk factor for nocturia, while an association between NP and brain natriuretic peptide levels has also been reported in patients with nocturia. Hypertension is now viewed as a disorder of blood vessels and treatment is directed at the vasculature rather than the blood pressure, with the latter currently serving as a biomarker for arterial injury. Nocturia is thought to be associated with the beginning of this cardiovascular continuum as studies have reported a link between coronary heart disease and nocturia. Therefore, there is an increasing need to elucidate the complex mechanisms implicated in the association between nocturia and hypertension to promote the development of more individualized therapies for the treatment of nocturia.

Comparison of nocturia etiology in black and white male patients.

INTRODUCTION: Much of what is known about the etiology of nocturia (i.e., nocturnal polyuria [NP], small bladder capacity [SBC], etc.) at the population level stems from the Krimpen study, which enrolled aging males from a homogenous municipality in the Netherlands. Given the higher prevalence of benign prostatic hyperplasia and overactive bladder in black versus white males in population research, we aim to test the hypothesis that black males seeking treatment for lower urinary tract symptoms (LUTS) are more likely to have nocturia owing to SBC. MATERIALS AND METHODS: We retrospectively analyzed 24 hour frequency-volume charts (FVCs) completed by males seeking treatment for LUTS at a Veterans Affairs urology clinic from 2008-2016. Patients were included if they were ≥ 18 years, identified as either Caucasian or African American, and had a complete baseline FVC showing ≥ 1 nocturnal void. Patients were stratified by race and classified as having nocturia owing to SBC (defined by a maximum voided volume < 200 mL or a nocturnal bladder capacity index > 1.3); NP (defined by a nocturnal polyuria index > 0.33); 'mixed' (SBC + NP); or 'other' (neither SBC nor NP). RESULTS: Between white and black patients, 28 (24%) versus 28 (26%) had NP, 32 (27%) versus 33 (30%) had SBC, and 35 (30%) versus 30 (28%) had mixed nocturia. Overall, there was no difference in distribution of underlying etiology by race (p = 0.51). CONCLUSIONS: Our results demonstrate no difference in the etiology of nocturia between black and white males. Accordingly, race should not play a role in the evaluation of patients seeking treatment for nocturia.

Overnight Urge Perception in Nocturia Is Independent of Depression, PTSD, or Anxiety in a Male Veterans Administration Population.

STUDY OBJECTIVES: The goal of this study was to compare the urge perception associated with nocturnal voiding at the time of voiding in individuals with and without depression, posttraumatic stress disorder (PTSD), or anxiety diagnoses to test the hypothesis that patients with such diagnoses are more likely to experience insomnia-driven convenience voiding during the sleep period. METHODS: A database of voiding diaries with urge perception grades (UPGs) from 429 adult males seeking treatment for nocturia at a Veterans Affairs-based urology clinic was analyzed. The UPG categorizes perception for urinating from 0 (out of convenience) to 4 (desperate urge). Diaries completed by males age 18 years and older showing ≥ 2 nocturnal voids were included. Those included (n = 178) were divided into two cohorts based on the presence (n = 62) or absence (n = 116) of one or more previously established mental health diagnoses (depression, PTSD, or anxiety). The chi-square test was used to determine significance between groups. RESULTS: Patients with a mental health diagnosis were more likely to report convenience voiding compared to those without depression, PTSD, or anxiety (14.5% versus 0.8%, P < .01). However, most voids in both groups were associated with the perception of urinary urgency. There were no differences in urinary volumes or hourly rates of urine production between the groups. CONCLUSIONS: A relatively small subset of urology patients experience nocturnal voiding because they are awake for reasons other than the urge to void. Mental health factors had a substantial, albeit minimal, effect. Most nocturia reflects urgency to urinate rather than voiding by convenience.

Etiology of nocturia response in men with diminished bladder capacity.

AIMS: To test the hypothesis that patients with nocturia owing to diminished global or nocturnal bladder capacity improve via increased bladder capacity. METHODS: This is a retrospective analysis of voiding diaries completed at a VA urology clinic between 2008-2017. Inclusion required patients aged at least 18 years, male, undergoing treatment for nocturia, and having completed at least two 24-hour voiding diaries ≥1 month apart. Patients were divided into two cohorts: responders (any decline in nocturia) and non-responders (no change or any increase in nocturia). Patients were further sub-stratified as having low global bladder capacity (maximum voided volume [MVV] <200 mL) versus low nocturnal bladder capacity (nocturnal maximum voided volume [NMVV] <200 mL and MVV ≥200 mL). Wilcoxon rank-sum was applied with a Bonferroni correction to test significance. RESULTS: Forty pre- and post-treatment diaries from 27 patients, and 19 pre- and post-treatment diaries from 17 patients were identified as having low global and low nocturnal bladder capacity, respectively. Nocturia responders with low global bladder capacity demonstrated significant decline compared to non-responders in nocturnal urine volume (NUV) (-140 vs +75, P < 0.01) and nocturnal bladder capacity index (NBCi) (-0.59 vs +0.23, P < 0.01). Patients with low nocturnal bladder capacity similarly demonstrated decreased NUV (-30 vs +160, P = 0.04) and NBCi (-1.4 vs +0.33, P < 0.01). There was no significant change in MVV or NMVV for either group. CONCLUSIONS: Treatment directed at lowering nocturnal urine production and enabling patients to consistently void at capacity is a rational strategy to treat nocturia in patients with low bladder capacity.