Nocturia is the complaint of having to get up more than once during the night to micturition. Nocturia is a frequent lower urinary tract symptom of all genders and ages and increases with age. Nocturia affects quality of life and is a risk factor for sleep disorders, sexual dysfunction, depression, and metabolic syndrome. In the elderly patients, nocturia has been reported to cause falls and increase the risk of bone fractures. With the rapid change to an aging society, nocturia has become a very important symptom. Nocturia is caused by three factors: nocturnal polyuria (NP), bladder storage dysfunction, and sleep disorders, with cardiovascular disease also thought to play a role. NP is a condition in which a large amount of urine is voided during the main sleep period. Causes of NP include excessive fluid intake, diurnal changes in antidiuretic hormone, cardiovascular and drug-related causes. Treatment for nocturia has changed in recent years, with the introduction of desmopressin for the treatment for nocturia associated with NP in males. However, epidemiological studies on nocturia in the Japanese population are limited, and the characteristics of patients with nocturia and the incidence of NP remains unclear. Therefore, we conducted a multicenter retrospective study to investigate the patient characteristics and the incidence of NP in patients with nocturia. In addition, we examined the risk factors for NP.

This study was approved by the Institutional Review Board (approval number: 2021-053). In this multi-institutional observation study, patients presenting with nocturia as their main complaint at 17 institutions in Japan from January 2018 to December 2022 were enrolled. The following clinical data were collected in this study: age, sex, body mass index (BMI), performance status by Eastern Cooperative Oncology Group, prostate volume, residual urine volume, prostate specific antigen, estimated glomerular filtration rate (eGFR), medical history, and concomitant medications. The urinary frequency and voiding volume were evaluated using a bladder diary. The nocturnal polyuria index was used as the definition of NP in this study, with a baseline value of 0.33. The primary endpoint was incidence of NP in patients with nocturia. The secondary endpoints were characteristics of patients with NP and risk factors of NP. The risk factors for NP were examined using logistic regression analysis. The cutoff values for the clinical parameters were determined using a receiver operating characteristic curve analysis. A two-tailed P-value < 0.05 was regarded as a statistical significantly different.

In this study, 875 patients were included in the analysis, which excluded 34 patients with insufficient data from the 909 patients with nocturia. The demographic data of the enrolled patients are listed in Table 1. The incidence of the NP which was the primary end point of this study was 67.4%. When NP patients were divided by age, the proportions of NP for patients <50 years, 50 to 60 years, 60 to 70 years, 70 to 80 years, and 80≤ years were 38.1%, 55.3%, 56.7%, 67.0%, and 79.3%, respectively. Table 2 shows the results of a logistic regression analysis regarding risk factors for NP. In univariate analysis, age ≥78 years, BMI <23.0 kg/m2, eGFR <45mL/min/1.73m2, patients with hypertension, diabetes mellitus, ischemic heart disease, insomnia or cerebrovascular disease were significant risk factors for NP (P < 0.001, P < 0.001, P = 0.035, P = 0.006, P = 0.021, P = 0.004, P = 0.027, P = 0.001, respectively). In the multivariate analysis, age ≥78 years, BMI <23.0 kg/m2, patients with ischemic heart disease or with cerebrovascular disease were significant risk factors for NP (P < 0.001, P < 0.001, P = 0.014, P = 0.016, respectively).

In this study, the incidence of the NP was 67.4%. The proportion of NP in patients with nocturia from Europe, the United State, and Asia ranged from 76-88% (1,2), and the present results were comparable to these results. Multivariate analysis also showed that age ≥78 years, BMI <23.0 kg/m2, ischemic heart disease, and cerebrovascular disease were significant risk factors for NP in this study. Recently, the association between frailty and nocturia or NP has been reported. Similarly, older men with frailty burden treated with lower urinary tract symptoms have been reported to have higher nocturnal urinary volume (3). Low body weight is one of the diagnostic features of frailty, and the results of this study suggest that weight loss may be a risk factor for NP. Additionally, age, ischemic heart disease and cerebrovascular disease may be risk factors in NP as well as nocturia.

To the best of our knowledge, this is the largest multi-institutional study to investigate the incidence of NP in Japanese patients with nocturia. In Japanese patients with nocturia, the incidence of NP was similar to that reported from Europe, the United State, and Asia. Age ≥78 years, BMI <23.0 kg/m2, ischemic heart disease, and cerebrovascular disease were suggested as possible risk factors for NP.

Weiss JP, van Kerrebroeck PE, Klein BM, et al. Excessive nocturnal urine production is a major contributing factor to the etiology of nocturia. J Urol. 2011 Oct;186(4):1358-63.
Chang SC, Lin AT, Chen KK, et al. Multifactorial nature of male nocturia. Urology. 2006 Mar;67(3):541-4.
Monaghan TF, Wagg AS, Bliwise DL, et al. Association between nocturia and frailty among elderly males in a veterans administration population. Aging Clin Exp Res. 2020 Oct;32(10):1993-2000.

Continence 7S1 (2023) 100787
DOI: 10.1016/j.cont.2023.100787