Discussion:
Nocturia is a common health problem in world-wide and its prevalence vary between 8.9%-82.7% according to inclusion criteria, sex and age groups.7-9 In US the prevalence of nocturia (≥ 1 voids) was evaluated in different age and sex groups and detected in men as 56.8%, 70.2% and 82.7% in 20-39 years, 40-59 years and ≥ 60 years respectively; in women as 68.9%, 74.3% and 84.7% in 20-39 years, 40-59 years and ≥ 60 years respectively.8 The nocturia prevalence was noted as 28.4%, 17.6% and 8.9% for nocturia episodes ≥ 1, ≥ 2, or ≥ 3 respectively, in Turkey.9 The most common risk factors of nocturia are age, hypertension, higher body mass index (BMI), metabolic syndrome, diabetes mellitus and cerebrovascular and cardiovascular diseases.10,11 Also nocturia was found to be associated with increased risk of falls, fractures, driving accidents and mortality.12-14 Nocturia and nocturia-related morbidities lead serious economic burden on health care systems of countries.15-17 These nocturia related risks, morbidities and economic burden reveal the importance of timely evaluation and effective nocturia management. The main step of nocturia management is the classification of nocturia according to pathophysiology. Nocturia can be sub-classified into four pathophysiological mechanisms: global polyuria (an overall increase of urine production), nocturnal polyuria (an increase of urine production only at night), reduced bladder capacity and mixed of etiologies.3,18,19 One of the first studies about the classification of nocturia was published by Weiss et al at 1998.20 They classified the nocturia in three groups as nocturnal polyuria (NP), nocturnal detrusor overactivity (NDO) (including reduced bladder capacity) and mixed (NP+NDO) and retrospectively evaluated the data of 200 consecutive patientswith nocturia.20 They detected that 7% of patients had nocturnal polyuria, 57% of patients had NDO and 36% of patients had a mixed etiology.20 They did not add global polyuria in classification, evaluated it separately and they noted that 23% of patients had global polyuria. There were some differences in definitions of nocturia etiologies in this study; they defined nocturnal polyuria as > 33% of the 24-hour urine production and polyuria as >2500 cc urine output in 24 hours. The distribution of nocturia etiologies was different from our study because of definition criteria and the unsimilar subclassification of etiologies. Choi et al evaluated the classification of nocturia in male patients with lower urinary tract symptoms (LUTS).21 A total of 521 patients >18 years old were included in the study and 376 (72.2%) patients had nocturnal polyuria, 520 (99.8%) patients had reduced bladder capacity, 376 (72.2%) patients has mixed type and 45 (8.6%) patients had global polyuria. Unlike this study the most common type of nocturia was nocturnal polyuria in our study. The patient population may have a significant role in different results of the studies, as they included only male patients with LUTS however we evaluated both genders and not only patients with LUTS. Epstein et al compared the nocturia etiology in black and white male patients who admitted with LUTS between the years 2008 and 2016.22They subclassified nocturia as NP, RBC, mixed (NP+RBC) and other (neither RBC nor NP) and they reported that 24%, 27%, 30% and 19% of white patients had NP, RBC, mixed nocturia and other etiologies respectively; while 26%, 30%, 28% and 16% of black patients had NP, RBC, mixed nocturia and other etiologies respectively. They noted that the etiological mechanisms were similar between the groups. The differences between the percentages of nocturia etiologies form our study may be also due to the selection of patient criteria and the differences in the classification of nocturia mechanisms. So we believe that the standardization of classification of nocturia mechanisms is important to speak the same language.
Nocturia has negative impacts on quality of life (QoL) of patients and leads to decrease in productivity at work.5,15,16,23,24 The effects of nocturia on QoL are mostly related with the severity of nocturia. Although one or more times wake up to void at night is defined as nocturia; it was noted that most of the patients with one nocturia episode had no bother or some of the older patients considered this as a normal consequence of aging.5,23,24 Tikkinen et al. evaluated the association between the nocturia severity and the health related QoL (HRQoL) of individuals with using generic 15 dimension instrument.5 Bother of nocturia was evaluated with four-point scale (none, small, moderate, major) and they noted that majority of patients with one nocturia episode had no significant bother however patients with two episodes of nocturia had small bother and patients with three or more nocturia episodes had moderate or major bother. Also they reported that ≥2 voids per night were associated with impaired HRQoL. We classified the nocturia severity as mild, moderate and severe in our study and reached similar results as they did. Additionally, we used a nocturia specific quality of life questionnaire, N-QoL, which was firstly described by Abraham et al25and we found that increased severity of nocturia was associated with impaired QoL of patients in concordance with previous studies.5,25 Zhang et al evaluated the prevalence and risk factors of nocturia and nocturia-related quality of life in Chinese population with 1198 adults.26 They used also N-QoL questionnaire and they reported that increasing episodes of nocturia and decreasing total sleeping hours were independent factors predicting a significantly lower N-QOL score. Also they noted that two or more nocturia episodes were associated with worse N-QoL scores as we did. Fitzgerald et al evaluated the data of 5506 adults at ages 30 to 79 from Boston Area Community Health (BACH) study; they detected the nocturia prevalence as 28.4% and the individuals with nocturia had lower self-rated mental and physical health scores.13However they did not specify the association with nocturia severity and these scores. Choi et al assessed the mediating role of sleep quality in the association between the nocturia and HRQoL with 500 patients above 40 years old.27 They reported that ≥2 nocturia episodes were associated with decreased HRQoL and this association was mediated by sleep quality. Although some of the studies presented the threshold ≥2 nocturia episodes for nocturia severity; there has been no consensus about the severity of nocturia and treatment requirements of patients regarding to nocturia severity in the existing literature yet. So, we propose a grading standardization for nocturia severity as mild (1-2 voids/night), moderate (3-4 voids/night) and severe nocturia (>4 voids/night) and demonstrate that increase in nocturia severity was associated with decreased quality of life as well as different rates of pathophysiological mechanisms.
We also faced that all scores for standardized LUTS questionnaires used in the present study were higher in more severe nocturia groups. Abdelmoteleb et al evaluated the association between the ICIQ-bladder diary and the ICIQ-LUTS.28 They noted that the agreement level between the ICIQ-bladder diary and the ICIQ-LUTS for nocturia symptoms was better than that of daytime frequency in both genders and the agreement level was also higher in at the extreme of frequencies. Both voiding and storage scores of ICIQ-MLUTS and ICIQ-FLUTS were also correlated with nocturia severity in our study. Given the fact that the severity of nocturia was diagnosed with a bladder diary in the present study, our findings support previous studies for the concordance of voiding questionnaires and bladder diary.
Several studies reported that the prevalence and severity of nocturia was increased with aging.9,29 Vaughan et al detected that the half of the patients with older age had ≥ 2 nocturia episodes however this rate was only 15-20% in younger patients. Also they noted that the number of co-morbidities were higher in patients with more nocturia frequency. Patients with moderate and severe nocturia were older and had more comorbidities need to treat than mild nocturia in our study.
Although the treatment of baseline pathology is essential in patients with nocturia, precautions in lifestyle changes like restriction in evening fluid intake may be enough in mild nocturia. Pharmacological therapies are recommended after the failure of lifestyle changes and behavioral treatments.30 So the increase in nocturia severity negatively effects the patients’ quality of life and increased urinary symptom scores may cause the failure of lifestyle changes and behavioral treatments and may require additional treatments to lifestyle changes in patients with moderate and severe nocturia. As all physicians cannot evaluate patients with frequency-volume chart due to excessive daily work-load in some regions; grading of nocturia may help for management of patients in daily clinical practice.
Limitations: This study is not without limitations. Number of participants from eight centers seem less compared to previous studies. We believe that face-to-face design may overcome this limitation as more standardized data driven for the study. We also did not evaluate for sleep disorders specifically, as we aimed at looking for urological disorders. However, isolated nocturia group in the present study may reflect the sleep disorders as mentioned previously.
Conclusions: Nocturia has negative impacts on QoL of patients and the impact rises with the increase of nocturia severity. Nocturia-related pathophysiological factors may vary between mild, moderate and severe nocturia groups. We believe that nocturia grading with identification of subtypes may help for standardization of the diagnostic and treatment approach as well as for the design of future clinical trials.
Conflict of interest: none declared
Acknowledgements: none declared