Analysis of nocturia with 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration: concept for effective treatment modality

Authors


Abstract

Study Type – Therapy (case series)

Level of Evidence 4

What’s known on the subject? and What does the study add?

Main causes of nocturia are 24-hour polyuria, nocturnal polyuria, decreased bladder capacity and sleep disorder.

This study revealed that nocturia is closely related to four factors, namely, 24-hour urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration and evaluation of all these factors through analysis of bladder diaries is clinically important to decide which is the main contributing factor in patients with nocturia and to determine suitable treatment modality on an individual basis.

OBJECTIVE

• To determine the relationship between the number of nocturia and 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration as well as to assess the significance of these factors with respect to eliminating nocturnal voidings in individual patients with nocturia.

PATIENTS AND METHODS

• Among 532 participants who completed a 3-day bladder diary between April 2005 and December 2006, the diaries of 450 participants without 24-h polyuria were analyzed.

• Clinical variables such as the number of daytime and night-time voids, 24-h urine volume, nocturnal polyuria index, daytime and night-time maximum voided volumes (MVV), night/day MVV ratio, sleep duration and proportion of night/day urine production rates were obtained from each diary.

• Participants were classified into eight groups according to values of three factors: nocturnal MVV, proportion of night/day urine production rates and length of sleep duration.

• Each group was divided into three subgroups: non-nocturics (number of nocturnal voidings is zero), mild nocturics (number of nocturnal voidings is one) and severe nocturics (number of nocturnal voidings is two or more).

• The data from non-nocturics with three normal factors were regarded as the normal control and compared with the variables of the other subgroups using Dunnett’s method.

RESULTS

• Variables that form the basis of classifying participants into eight groups and corresponding to abnormal factors of each group were statistically significant in all the subgroups of each group.

• Furthermore, a significantly increased 24-h urine volume was found in severe nocturics of the group with three normal factors.

• A significantly decreased 24-h urine volume was found in non-nocturics of groups with nocturnal polyuria, decreased bladder capacity and both long sleep duration and nocturnal polyuria.

• A significantly increased nocturnal MVV and night/day MVV ratio were shown in non-nocturics and mild nocturics of the groups with nocturnal polyuria and both long sleep duration and nocturnal polyuria.

CONCLUSIONS

• Because nocturia is a multifactorial disorder and closely related to four factors (i.e. 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration), the evaluation of all these factors appears to be clinically useful for determining the main contributing factor in patients with nocturia as well as the suitable treatment modality on an individual basis.

• Physicians should take all these factors into consideration in the evaluation and treatment of nocturia.

Abbreviations
HRQL

health-related quality of life

MVV

maximum voided volume

NPi

nocturnal polyuria index

OAB

overactive bladder

INTRODUCTION

Nocturia, defined by the ICS as the complaint of waking one or more times to void during sleeping, is a common disorder affecting both elderly men and elderly women [1–3]. Nocturia leads to sleep deprivation and diurnal fatigue, a decreased health-related quality of life (HRQL), increased risk of fall at night and an increased mortality rate, and is perceived to be an important health problem in elderly individuals [2–6].

Various factors relating to nocturia include local diseases such as BPH and overactive bladder (OAB); systemic diseases such as hypertension, diabetes mellitus, heart failure, renal failure, peripheral oedema, nephrotic syndrome, hypoproteinaemia and liver diseases; as well as obstructive sleep apnoea and false dietary habits, such as excessive intakes of water, salt, alcohol and caffeine [1–3]. There are also many factors resulting in sleep disturbances and leading to nocturia, such as various kinds of pain and pruritus, pulmonary diseases subsequent to a cough, heartburn and sleep disorders, as well as mental problems, including depression, higher susceptibility to light and noise, caregiving duties for a family member, etc [7]. Therefore, nocturia has been recognized recently not only as a symptom of lower urinary tract disorders, but also as a troublesome clinical entity to which special attention should be paid with respect to its evaluation and management.

Numerous clinical studies have shown that the main causes of nocturia are 24-h polyuria, nocturnal polyuria, decreased bladder capacity and sleep disorder [1–3,7,8]. In particular, nocturnal polyuria appears to be the key factor relating to nocturia [8]. It is also well known that analysis of a bladder diary clarifies these causes of nocturia and provides physicians with useful information for the evaluation and treatment of patients [2,3].

Total sleep duration is one of the sleep parameters that can be obtained from a bladder diary [9]. The ICS considers 8 h to be the normal sleep duration for evaluating nocturia [1]; however, actual sleep duration varies among individuals. Sleep duration of the elderly tends to be prolonged because of various factors that cause sleep disturbances, as noted above, and its elongation may lead to nocturnal polyuria [9]. Therefore, nocturnal urine volume and length of sleep duration should be taken into consideration to determine the cause of nocturia.

In a previous study, an analysis of bladder diaries of participants who underwent a mass screening programme, and outpatients who visited our clinic, confirmed that sleep duration is an independent factor relating to the number of nocturnal voidings [9]. In the present study, the same participants were re-investigated using 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration, and the significance of these factors was assessed with respect to reducing or eliminating nocturnal voidings during sleep in individual patients with nocturia.

PATIENTS AND METHODS

The present study was performed under the approval of the Ethical Committee of Meiji University of Integrative Medicine.

The methods by which participants were enrolled and data were analyzed in this study have been reported previously [9]. Briefly, between April 2005 and December 2006, 694 participants including 619 community-dwelling people who underwent a mass screening programme in a rural town in Hokkaido, Japan, and 75 outpatients who consulted the Department of Urology, Meiji University of Integrative Medicine, with various complaints including nocturia were requested to complete a 3-day bladder diary. Written informed consent to analyze and publish the data obtained from each bladder diary was obtained from 673 of the 694 participants.

The diary was returned by the participants. The data were analyzed from the day when the number of 24-h voids showed the median value for the 3 days. Clinical variables such as the frequency of daytime and night-time voids, 24-h, diurnal and nocturnal urine volumes, daytime and night-time maximum voided volumes (MVV) and sleep duration were obtained from each diary. The first void after waking was included in the number of daytime voids and nocturnal urine volume. Night/day MVV ratio was calculated from the diary data. Nocturnal polyuria index (NPi) was calculated by dividing noctural urine volume by 24-h urine volume. Sleep duration was defined as the interval between going to bed with the intent of sleeping and getting up, and obtained by calculation using the times recorded in the bladder diary.

Participants with a 24-h urine volume >40 mL/kg body-weight were diagnosed as having 24-h polyuria. Those with a proportion of night-time urine production rate (mL/min) and daytime production rate (mL/min) >1 were diagnosed as having nocturnal polyuria. Hence, there were no universally accepted criteria: decreased bladder capacity was defined as nocturnal MVV <300 mL and prolonged sleep duration as >480 min.

The participants with 24-h polyuria were excluded from the present study, and the remaining participants were classified into eight groups according to nocturnal MVV, proportion of night/day urine production rates and length of sleep duration (Table 1). Group A were those without decreased bladder capacity, nocturnal polyuria and prolonged sleep duration. Group B were those with prolonged sleep duration. Group C were those with nocturnal polyuria. Group D were those with decreased bladder capacity. Group E were those with prolonged sleep duration and nocturnal polyuria. Group F were those with prolonged sleep duration and decreased bladder capacity. Group G were those with decreased bladder capacity and nocturnal polyuria. Group H were those with three abnormal factors. The variables obtained from the bladder diaries of the eight groups were summarized. The participants of each group were divided into three subgroups: non-nocturics (number of nocturnal voidings is zero), mild nocturics (number of nocturnal voidings is one) and severe nocturics (number of nocturnal voidings is two or more). The data obtained from the non-nocturics in group A were regarded as the normal control and compared with the variables of the other subgroups using Dunnett’s method. ANOVA was also used to determine the relationship between the variables and the frequency of nocturia. All data are reported as the mean ± SD. P < 0.05 was considered statistically significant.

Table 1. Classification of the participants
GroupNocturnal MVV (mL)Proportion of night/day urine production ratesSleep duration (min)Number of participants
All (%)Non- nocturicsMild nocturicsSevere nocturics
  1. MMV, maximum voided volume.

A≥300<1<48075 (16.7)61122
B≥300<1>48031 (6.9)12145
C≥300>1<480137 (30.4)596216
D<300<1<48061 (13.6)34243
E≥300>1>48062 (13.8)103022
F<300<1>48029 (6.4)8165
G<300>1<48033 (7.3)91311
H<300>1>48022 (4.9)0220
Total450 (100)19317384

RESULTS

Among the 694 subjects who were asked to record a 3-day bladder diary, 162 participants who were suspected of suffering from definite pathological disorders such as cancer of the bladder, bladder stone, bacterial cystitis, cancer of the prostate and prostatitis, and who did not complete the 3-day bladder diary and/or who did not consent to participation in the study were excluded from the analysis [9]. Among 532 eligible participants, 82 were diagnosed as having 24-h polyuria and also were excluded. Finally, data obtained from 450 participants were analyzed in the present study.

Detailed characteristics of the 532 participants including those with 24-h polyuria were reported in a previous study [9]. Among the 450 participants adopted in the present study, the numbers of non-nocturics, mild nocturics and severe nocturics were 193, 173 and 84, respectively. The numbers of participants who were non-nocturics, mild nocturics and severe nocturics in each group are summarized in Table 1.

Age, gender and nine variables obtained from the bladder diaries of the eight groups are summarized in Table 2. Mean ± SD numbers of nocturia in participants with no abnormal factor (group A), those with one abnormal factor (a total of groups B, C and D), those with two factors (a total of groups E, F and G) and those with three factors (group H) were 0.2 ± 0.5, 0.7 ± 0.7, 1.2 ± 1.0 and 3.1 ± 1.5, respectively. A statistically significant relationship was observed between number of factors and frequency of nocturia (ANOVA, P < 0.0001).

Table 2. Participant characteristics
VariableGroup
ABCDEFGH
  1. Data are the mean ± SD except where indicated. MMV, maximum voided volume; NPi, nocturnal polyuria index.

Number of participants75311376162293322
Gender (male/female)26/4915/1636/10120/4129/3313/1614/1916/6
Age (years)61.8 ± 10.063.5 ± 10.961.8 ± 9.361.3 ± 10.966.3 ± 9.868.3 ± 10.763.8 ± 10.374.6 ± 5.6
24-h urine volume (mL)1642 ± 3521644 ± 4301545 ± 364 1182 ± 3371510 ± 371 1138 ± 328 1198 ± 4071291 ± 361
NPi (%)24.4 ± 4.230.8 ± 6.339.0 ± 9.921.2 ± 5.650.8 ± 10.626.7 ± 7.138.0 ± 12.450.5 ± 9.6
Number of daytime voids 6.6 ± 2.05.7 ± 1.65.7 ± 1.26.6 ± 2.05.2 ± 1.46.1 ± 1.86.0 ± 1.76.7 ± 1.9
Number of night-time voids 0.2 ± 0.50.8 ± 0.70.7 ± 0.70.5 ± 0.61.3 ± 0.91.0 ± 0.91.3 ± 1.13.1 ± 1.5
Daytime MVV (mL)313 ± 97338 ± 80286 ± 97246 ± 87251 ± 89235 ± 82219 ± 79165 ± 47
Nocturnal MVV (mL)380 ± 90388 ± 79443 ± 102205 ± 44432 ± 100180 ± 49224 ± 43206 ± 50
Night/day MVV ratio 1.3 ± 0.41.2 ± 0.31.7 ± 0.60.9 ± 0.31.9 ± 0.80.8 ± 0.41.2 ± 0.51.3 ± 0.3
Sleep duration (min)430 ± 40543 ± 54401 ± 59419 ± 46526 ± 32540 ± 50397 ± 70544 ± 37
Proportion of night/day urine production rates 0.8 ± 0.20.8 ± 0.21.8 ± 0.80.7 ± 0.22.0 ± 1.10.6 ± 0.21.8 ± 1.11.8 ± 0.8

Age and eight variables of each subgroup in the eight groups and the results of multiple comparisons between non-nocturics of group A and the other subgroups using Dunnett’s method are shown in Table 3. Variables that form the basis for classifying participants into the eight groups and corresponding to the abnormal factor of each group were statistically significant in all subgroups of each group. Furthermore, a significantly increased 24-h urine volume was found in severe nocturics of group A. A significantly deceased 24-h urine volume was found in non-nocturics of groups C, D and E. A significantly increased nocturnal MVV and night/day MVV ratio were shown in non-nocturics and mild nocturics of groups C and E (Table 3).

Table 3. Multiple comparisons between non-nocturics of group A and other subgroups
VariableGroup
ABCDEFGH
  1. Data are the mean ± SD except where indicated. MMV, maximum voided volume; NPi, nocturnal polyuria index; NS, not significant.

Non-nocturics        
 Number of participants6112593410890
 Age (years)61.0 ± 10.159.8 ± 10.657.8 ± 8.557.1 ± 10.356.3 ± 6.662.4 ± 15.758.9 ± 11.3
 PNSNSNSNSNSNS
 24-h urine volume (mL)1616 ± 3411428 ± 3521390 ± 3591109 ± 3211092 ± 293939 ± 1641036 ± 389
 PNS0.002<0.0001<0.0001<0.0001<0.0001
 NPi (%)23.9 ± 4.228.9 ± 3.433.6 ± 5.620.1 ± 5.046.3 ± 10.720.6 ± 4.428.4 ± 9.2
 P0.025<0.00010.010<0.0001NSNS
 Number of daytime voids6.5 ± 1.55.3 ± 1.15.5 ± 1.26.1 ± 1.14.7 ± 1.55.3 ± 0.95.4 ± 1.1
 P0.012<0.0001NS<0.0001NSNS
 Daytime MVV (mL)317 ± 94337 ± 85293 ± 106253 ± 81220 ± 77258 ± 96236 ± 105
 PNSNS0.0110.018NSNS
 Nocturnal MVV (mL)383 ± 90408 ± 87454 ± 104213 ± 44484 ± 106201 ± 61232 ± 30
 PNS<0.0001<0.00010.004<0.0001<0.0001
 Night/day MVV ratio1.3 ± 0.31.3 ± 0.31.7 ± 0.50.9 ± 0.32.4 ± 0.90.8 ± 0.31.1 ± 0.4
 PNS<0.00010.002<0.0001NSNS
 Sleep duration (min)429 ± 41516 ± 24378 ± 61402 ± 41518 ± 23532 ± 41329 ± 79
 P<0.0001<0.0001NS<0.0001<0.0001<0.0001
 Proportion of night/day urine production rates0.8 ± 0.20.7 ± 0.11.5 ± 0.40.7 ± 0.21.7 ± 0.90.5 ± 0.11.4 ± 0.3
 PNS<0.001NS<0.001NS<0.001
Mild nocturics        
 Number of participants121462243016132
 Age (years)64.3 ± 9.066.0 ± 10.963.9 ± 8.766.0 ± 9.765.6 ± 8.968.9 ± 7.660.5 ± 8.768.5 ± 4.9
 PNSNSNSNSNS0.007NSNS
 24-h urine volume (mL)1653 ± 3071736 ± 4451620 ± 3051259 ± 3401537 ± 3371160 ± 2891232 ± 3731175 ± 177
 PNSNSNS<0.0001NS<0.00010.002NS
 NPi (%)25.9 ± 3.430.7 ± 8.140.9 ± 9.322.7 ± 6.248.8 ± 9.128.0 ± 7.138.4 ± 6.440.5 ± 3.5
 PNS<0.0001<0.0001NS<0.00010.007<0.0001<0.0001
 Number of daytime voids7.1 ± 3.65.9 ± 1.66.0 ± 1.16.7 ± 1.85.3 ± 1.26.2 ± 1.85.4 ± 1.74.5 ± 0.7
 PNSNS0.032NS<0.0001NS0.035NS
 Daytime MVV (mL)283 ± 107331 ± 80284 ± 92247 ± 94273 ± 79235 ± 82245 ± 54240 ± 14
 PNSNSNS0.005NS0.0030.016NS
 Nocturnal MVV (mL)353 ± 71380 ± 79446 ± 99202 ± 40436 ± 99171 ± 37225 ± 50245 ± 64
 PNSNS0.001<0.00010.023<0.0001<0.00010.042
 Night/day MVV ratio1.4 ± 0.51.2 ± 0.21.7 ± 0.70.9 ± 0.21.7 ± 0.50.8 ± 0.51.0 ± 0.31.0 ± 0.3
 PNSNS<0.0001<0.00010.003<0.00010.027NS
 Sleep duration (min)438 ± 35562 ± 60414 ± 50435 ± 44528 ± 31536 ± 52415 ± 55525 ± 21
 PNS<0.0001NSNS<0.0001<0.0001NS0.003
 Proportion of night/day urine production rates0.8 ± 0.20.7 ± 0.21.9 ± 0.90.7 ± 0.21.8 ± 0.70.7 ± 0.21.6 ± 0.31.2 ± 0.1
 PNSNS<0.0001NS<0.0001NS<0.0001NS
Severe nocturics        
 Number of participants251632251120
 Age (years)71.5 ± 9.265.6 ± 11.768.0 ± 8.971.7 ± 3.271.7 ± 8.576.0 ± 3.271.6 ± 6.675.3 ± 5.4
 PNSNS0.016NS<0.00010.0020.002<0.0001
 24-h urine volume (mL)2375 ± 1771908 ± 3781829 ± 3451403 ± 3911662 ± 3131390 ± 4821291 ± 4551302 ± 376
 P0.005NS0.042NSNSNS0.0150.002
 NPi (%)30.5 ± 2.135.6 ± 3.251.6 ± 10.622.4 ± 5.655.6 ± 11.032.3 ± 3.745.2 ± 15.451.5 ± 9.5
 PNS<0.0001<0.0001NS<0.00010.001<0.0001<0.0001
 Number of daytime voids6.5 ± 2.16.2 ± 2.65.8 ± 1.4 11.7 ± 4.25.4 ± 1.67.4 ± 2.57.1 ± 1.66.9 ± 1.9
 PNSNSNS<0.00010.004NSNSNS
 Daytime MVV (mL)375 ± 177358 ± 81271 ± 80160 ± 79234 ± 101200 ± 59175 ± 67158 ± 42
 PNSNSNS0.0110.0010.013<0.0001<0.0001
 Nocturnal MVV (mL)475 ± 177360 ± 65388 ± 89150 ± 50404 ± 92176 ± 62216 ± 46202 ± 49
 PNSNSNS<0.0001NS<0.0001<0.0001<0.0001
 Night/day MVV ratio1.3 ± 0.11.0 ± 0.31.6 ± 0.51.0 ± 0.22.0 ± 1.00.9 ± 0.31.4 ± 0.71.3 ± 0.3
 PNSNSNSNS<0.0001NSNSNS
 Sleep duration (min)450 ± 42554 ± 73436 ± 51480 ± 0529 ± 36565 ± 59431 ± 33546 ± 38
 PNS<0.0001NSNS<0.0001<0.0001NS<0.0001
 Proportion of night/day urine production rates1.0 ± 0.040.9 ± 0.12.7 ± 1.00.6 ± 0.22.5 ± 1.40.8 ± 0.22.4 ± 1.81.9 ± 0.8
 PNSNS<0.0001NS<0.0001NS<0.0001<0.0001

DISCUSSION

In the present study, both participants in a mass screening programme and outpatients at our clinic were analyzed simultaneously using the same form of bladder diary and instruction manual. The participants in both groups were considered to comprise a consecutive series and were analyzed together to avoid selection bias [9].

The present study aimed to analyze the causes of nocturia accurately and to determine an effective treatment modality for eliminating nocturnal voidings during sleeping in individual patients. Accordingly, the nocturics were divided into two groups, comprising those with one nocturnal voiding (mild nocturics) and those with two or more voidings (severe nocturics), because the factors that can cause nocturia such as 24-h urine volume, nocturnal urine volume, bladder capacity and length of sleep duration differ between the groups (Table 3). Troubled sleeping, an impaired quality of sleep and HRQL as a result of nocturia were not used to classify the participants.

Numerous studies have shown that the causes of nocturia are 24-h polyuria, nocturnal polyuria, decreased bladder capacity and sleep disorders [1–3,7,8]. According to the present analysis, those individuals that exhibited more factors that can cause nocturia tended to have more frequent nocturia. Therefore, close attention should be paid to all four factors when treating patients with nocturia.

Among these factors, 24-h polyuria appears to be related to apparent pathological disorders such as diabetes mellitus, diabetes insipidus, psychogenic polydipsia and habitual excess intake of fluid, and is easily distinguished from other causes of nocturia by analysis of a bladder diary. Therefore, participants with 24-h polyuria were excluded from the present study to simplify analysis. However, 24-h urine volume was related to nocturia in the present study and participants with one or two factors that can cause nocturia and small 24-h urine volume did not have nocturia (Table 3). Because of the statistically significant results, 24-h urine volume appears to be closely related to the presence or absence and severity of nocturia even in those individuals without 24-h polyuria. Hashim et al.[10] performed a randomized controlled cross-over trial in which patients with OAB increased or reduced fluid input and reported that a reduction in fluid intake by 25% is a useful way of improving nocturia, daytime frequency and urgency. An appropriate reduction of 24-h urine volume appears to be important as a useful treatment modality in nocturia. Careful assessment of daily life and education for the improvement of food and water intakes are considered to be essential for patients with nocturia.

Nocturnal polyuria appears to be the key factor in evaluating nocturia [8]. We used the proportion of night/day urine production rates to determine nocturnal polyuria. Natsume et al.[11] performed a hypertonic saline infusion test on 50 patients with nocturia and reported that there was a significantly increased nocturnal diuretic rate compared to the daytime diuretic rate in the nocturnal polyuria group and a significantly decreased nocturnal diuretic rate compared to the daytime rate in the non-nocturnal polyuria group [11]. Natsume et al.[11] also reported that the diuretic rate in the daytime in the noctural polyuria group was similar to that in the non-nocturnal polyuria group despite the greater 24-h total urine output, which suggested a decreased diuretic rate in daytime and an excessive nocturnal diuretic rate in the nocturnal polyuria group. Other studies showed that patients with nocturnal polyuria have a marked tendency of daytime excessive water retention or peripheral oedema, leading to nocturnal diuresis [12,13]. Differences in physiological factors such as blood pressure, renal blood flow, peripheral circulation, osmotic pressure, secretion and sensitivity of arginine vasopressin, etc., between sleeping and wakefulness appear to play major roles in the nocturnal overproduction of urine [11–13]. It is plausible that patients with nocturnal polyuria continue to exhibit increased diuresis during sleeping and decreased diuresis during wakefulness. Therefore, the proportion of nocturnal and diurnal diuretic rates appears to be a good indicator of the severity of nocturnal polyuria. Furthermore, a previous study clarified that sleep duration is an independent factor associated with nocturia [9] and NPi changes according to the length of sleep duration. Accordingly, the proportion of night/day urine production rates, rather than NPi, was used to diagnose nocturnal polyuria. However, the present study did not aim to determine the definition of nocturnal polyuria, and further studies are necessary to define nocturnal polyuria appropriately. Because it is considered difficult for the elderly to improve the aforementioned physiological factors intentionally, it is necessary to provide not only advice concerning daily life and intakes of water, alcohol, caffeine and salt, but also special measures such as afternoon rest with leg raising, the use of elastic bandages and the administration of diuretics or anti-diuretic hormone for improving physiological factors in the treatment of nocturnal polyuria [2,3,10,13].

Decreased nocturnal bladder capacity is also a major factor associated with nocturia. BPH and OAB are two main diseases leading to decreased bladder capacity in elderly individuals. At present, the administration of α1 blockers for BPH and anti-muscarinic agents for OAB may be useful as pharmacological therapy for nocturia in these patients [2,3,14–17]. Bladder training and deep sleep as a result of exercise such as walking or jogging and the administration of hypnotics also appear to be effective for increasing bladder capacity at night [2,17–19].

A previous study clarified that the length of sleep duration is a definite factor associated with nocturia [9]. Elderly individuals generally spend more time in bed and less time asleep than younger individuals. Sleep in the elderly tends to be shallow and easily fragmented [20,21]. Hoch et al.[22] treated 21 normal elderly individuals with 30 min of restriction in bed and reported that modest sleep restriction led to sustained improvements in sleep continuity and depth [22]. Sugaya et al.[19] reported that deeper sleep as a result of a walking exercise appeared to increase bladder capacity during sleeping and raise the arousal threshold [19]. Therefore, sleep restriction is considered to be one of the options representing a useful treatment modality for nocturia.

Participants were classified into eight groups using the aforementioned three factors and the variables of each group were analyzed in detail to determine the appropriate treatment modality on an individual basis.

In the group with three normal factors (group A), significantly increased 24-h urine volume was seen in the subgroup of severe nocturics (Table 3). When the 24-h urine volume of severe nocturics (2375 mL) is reduced to that of non-nocturics (1616 mL), the nocturnal urine volume of severe nocturics is calculated as 484 mL, which is almost equal to the nocturnal MVV of severe nocturics. Therefore, a reduction in 24-h urine volume appears to be the sole effective treatment modality in this group [10].

In the group with long sleep duration (group B), significantly long sleep and elevated NPi were found in all subgroups. The proportion of night/day urine production rates of all subgroups were <1. NPi of non-nocturics and mild nocturics was <33%. When sleep duration of severe nocturics (554 min) is reduced to that of control (429 min), NPi is calculated to be 27.6%. Therefore, long sleep duration appears to be the main problem in group B. Shallow sleep as a result of the prolongation of sleep duration may be a cause of waking up at night [21]. Reducing the duration of sleep appears to be necessary in this group [22].

In the group with nocturnal polyuria (group C), both the proportion of night/day urine production rates and NPi were significantly elevated in all subgroups. There was also a statistically significant relationship between proportion of night/day urine production rates and the frequency of nocturia in this group (ANOVA, P < 0.0001) and the proportion was extremely high (2.7) in severe nocturics. On the other hand, sleep duration was short in non-nocturics or not different in mild and severe nocturics compared to that of the control group. An improvement of nocturnal polyuria using various modalities is considered to be necessary in this group [2,3,13]. According to the analysis of groups B and C, it is probable that NPi could not be used to differentiate between true nocturnal polyuria and long sleep duration. Therefore, we consider that patients with elevated NPi should be determined using proportion of night/day urine production rates and sleep duration. Furthermore, 24-h urine volume was small and nocturnal MVV and night/day MVV ratio were large in non-nocturics. Decreasing the 24-h urine volume and an enlargement of nocturnal bladder capacity may be useful for improving nocturia in group C.

In the group with decreased bladder capacity (group D), daytime MVV and nocturnal MVV were small in all subgroups. The number of daytime void was increased in severe nocturics. It is speculated that participants in this group suffer from OAB and non-nocturics escape night-time urination because of an extremely decreased 24-h urine volume (Table 3). It is apparent that participants who were mild and severe nocturics in group D can escape nocturia when their nocturnal MVVs become equivalent to that of the control (383 mL) because their nocturnal urine volume was in the range 286–314 mL. An increase in nocturnal bladder capacity is necessary for treating this group.

In the group with long sleep duration and nocturnal polyuria (group E), a significantly prolonged sleep duration and an increased proportion of night/day urine production rates and NPi were observed in all subgroups (Table 3). It is interesting that significantly increased night/day MVV ratio was also found in three subgroups (Table 3). Participants of this group tried to increase their bladder capacity at night; however, the increase appeared to be insufficient to prevent nocturia. Therefore, improvements of both prolonged sleep duration and nocturnal polyuria appear to be necessary for treating this group. A small 24-h urine volume was also found in non-nocturics of group E (Table 3). Decreasing the 24-h urine volume may be useful for treating some patients in this group.

In the group with long sleep duration and decreased bladder capacity (group F), a significant elongation of sleep duration and decreased nocturnal MVV were found in three subgroups. Improvements of these two factors appear to be necessary for treating this group. A decreased 24-h urine volume was also found in non-nocturics and mild nocturics. However, 24-h urine volumes of three subgroups (939, 1160 and 1390 mL, respectively) were similar and a reduction in 24-h urine volume does not appear to be practical in this group.

In the group with nocturnal polyuria and decreased bladder capacity (group G), a significantly increased proportion of night/day urine production rates and decreased nocturnal MVV were found in three subgroups. Furthermore, a significant decrease in 24-h urine volume was also observed in all subgroups. Therefore, a reduction in total urine volume is appropriate in this group for avoiding nocturia. A significantly short sleep duration is also found in non-nocturics of this group. Extreme reductions in 24-h urine volume (1036 mL) and sleep duration (329 min) appear to prevent this group from suffering from nocturia (Table 3); however, these measures are not likely to be practical for treating nocturia. Improvements of nocturnal polyuria and decreased bladder capacity appear to be the main treatment modalities in this group.

In the group with three abnormal factors (group H), 91% (20/22) of the participants were severe nocturics. A significantly decreased 24-h urine volume was found in severe nocturis, however, it appeared to be inefficient for avoiding nocturia. Therefore, an improvement of all three factors appears to be necessary for this group to avoid nocturia.

Recently, Vaughan et al.[23] treated 55 patients with two or more episodes of nocturia with both behavioural intervention and drug therapy and reported that multicomponent intervention is effective in reducing the frequency of nocturia. Such a behavioural intervention would simultaneously improve 24-h polyuria, nocturnal polyuria and sleep disorder, and probably also decrease nocturnal bladder capacity [23]. The results of the present study showed that nocturics usually have several factors that can cause nocturia, which appears to support the usefulness of multicomponent therapy. However, the limitation of multicomponent intervention is the difficulty in deciding which component is appropriate for each patient. The classification used in the present study is considered to be clinically useful for determining the predominant factors and the suitable treatment for each patient. Accordingly, it is proposed that four factors (i.e. 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration) should be carefully determined in each patient for determining the treatment modality on an individual basis. The numerical data shown in Table 3 are also considered to be applicable as a nomogram explaining the relationship between the severity of nocturia and all four factors, when evaluating patients. Careful analysis of detailed bladder diary to determine lifestyle, including urination, food and water intakes, physical exercise, sleep condition, etc., is considered to be of help for determining an effective treatment strategy.

One of the limitations of the present study is that the true causes of waking up at night were not examined in the participants [9]. Consequently, it is difficult to predict which factor contributes most to nocturia in each participant. It is plausible that the classification of the participants into eight groups using nocturnal urine volume, nocturnal bladder capacity and length of sleep duration, as well as detailed analyses of the variables obtained from a bladder diary, could identify the predominant factors causing nocturia in each group.

The other limitation of the present study is that troublesome sleep, sleep hygiene and impaired HRQL as a result of nocturia were not examined. Nocturia is most troublesome among LUTS and there are strong relationships between the frequency of nocturia and the degree of troublesome sleep, impaired quality of sleep and HRQL [24–29]. Recently, studies analyzing the relationship between nocturia and troublesome sleep or HRQL reported that two or more voidings at night constitutes clinically significant nocturia [24,25,29]. However, certain patients with one voiding also consider nocturia to be troublesome [28]. In particular, sleep insufficiency is closely related to troublesome nocturia [28], and improvements in troubled sleeping, such as reductions in the time to sleep initiation and the time to falling asleep after nocturnal voiding, an elongation of the time between falling asleep and the first awakening to void, an improvement of daytime fatigue, etc., are considered as another important therapeutic goal [23,26,28,29]. Behavioural therapy including exercise and the use of hypnotics should be applied for improvement [19,23]; however, a reduction or elimination of nocturia is considered to be directly linked to an improvement of trounblesome sleep and impaired HRQL. Therefore, the present study aimed to determine how to eliminate nocturnal voiding in individual patients. Further studies are necessary to confirm whether the treatment modality described in the present study is effective not only for reducing frequent nocturnal voiding, but also to improving troublesome sleep and disturbed HRQL as a result of nocturia. Furthermore, we used length of sleep duration to determine sleep condition. Sleep becomes prolonged and shallow in elderly individuals [20,21], and there may be some relationship between sleep duration and impaired quality of sleep. However, additional study is necessary to confirm this hypothesis.

In conclusion, an evaluation of all four factors (i.e. 24-h urine volume, nocturnal urine volume, nocturnal bladder capacity and length of sleep duration) appears to be clinically useful for determining which factor contributes most in patients with nocturia as well as for determining the suitable treatment modality on an individual basis. Physicians should take all these factors into consideration in the evaluation and treatment of nocturia.

CONFLICT OF INTEREST

None declared.