Nocturia has two major causes. One problem is with the nocturnal urine volume, and the other is a problem with bladder capacity during the night. Since multiple factors affect nocturia, what affects it most has not been well investigated. We have been studying the bladder storage function as a homeostatic system keeps micturition interval constant by increasing the bladder capacity during the diuretic phase1). We have shown that dysfunction of this homeostatic system is closely related to overactive bladder (OAB) and benign prostatic hyperplasia (BPH) in male patients with lower urinary tract symptoms (LUTS). We hypothesized that nocturnal diuresis could affect bladder storage function and cause nocturia. This study aimed to identify what factors are most associated with nocturia and investigate how strongly nocturnal diuresis affects bladder storage dysfunction as a factor related to nocturia.

Male patients with LUTS who were able to keep 24-h frequency-volume charts (FVCs) for 3 days were included in this study. Exclusion criteria were apparent neurogenic lower urinary tract symptoms, clean intermittent catheterization, and acute urinary tract infection. Uroflowmetry, ultrasonography to measure prostate volume, Overactive Bladder Symptom Score (OABSS) and 24-h FVCs were evaluated. OABSS evaluated OAB as a total score >3 and an urgency score >2. Nocturnal polyuria (NP) was diagnosed using the NP index (NPi) >0.33 definition (nocturnal urine volume >33% of total 24-hour urine volume). Patients who marked an average of two or more times per night on 3-days 24h-FVCs were defined as the nocturia (+) group, and those who marked less than two times were defined as the nocturia (-) group. Age, prostate volume, the prevalence of NP, and parameter of 24-h FVCs were compared between groups, with values of P<0.05 considered significant.

A total of 100 patients entered the study (nocturia (+) group: 52 patients; nocturia (-) group: 48 patients). The nocturia (+) group was significantly older, had a smaller prostate volume, and had a smaller single voided volume at night than the nocturia (-) group (nocturia (+) vs. nocturia (-): Age; 74.3 ± 7.2 years vs 77.8 ± 6.0 years, P=0.007. prostate volume; 38.7 ± 19.4 mL vs 30.5 ± 16.3 mL, P=0.02. single voided volume at night; 246.9 ± 79.7 mL vs. 211.45 ± 64.9 mL, P<0.001). The incidence of NP and nocturnal diuresis rate was significantly higher in the nocturia (+) group than in the nocturia (-) group (both P<0.001). Multivariate analysis showed that increased nocturnal diuresis rate and decreased nocturnal single voided volume were significantly related to nocturia in male LUTS patients (nocturnal diuresis rate: OR 6.48, P=0.011; decreased nocturnal single voided volume: OR 5.43, P=0.033). Even when limited to patients without NP, increased nocturnal diuresis rate and decreased nocturnal single voided volume were significantly related to nocturia (nocturnal diuresis rate: OR 6.48, P=0.011; decreased nocturnal single voided volume: OR 5.43, P=0.033). Nocturnal bladder storage dysfunction was defined as a single voided volume at night of 222.4 ml or less based on the ROC curve (AUC 0.66, sensitivity 62.5%, specificity 42.3%). Then, 16% of patients without daytime bladder storage dysfunction (≧200 ml daytime voided volume) showed bladder storage dysfunction only at night, and 67% developed NP.

This study consisted of elderly patients over 65 years old and showed that increased nocturnal diuresis rate and decreased nocturnal voided volume most affected nocturia. Increased nocturnal diuresis rate causes nocturnal polyuria, but the same results were obtained in patients without NP. Most of the patients with nocturia who developed nocturnal bladder storage dysfunction have daytime bladder dysfunction, but 16% of them did not have daytime bladder dysfunction. These results suggest that the pathophysiology specific to the nocturnal period, such as nocturnal diuresis, causes bladder storage dysfunction only at night. Although NP is a major cause of nocturia, NP with normal bladder storage function may not have a significant impact on nocturia in elderly male patients. We considered that nocturnal diuresis causing NP may have affected nocturia via bladder storage dysfunction.

Strategies focusing on nocturnal bladder storage dysfunction associated with increased nocturnal diuresis rate may be necessary for treating nocturia in elderly patients.

Matsuoka K, Akaihata H, Hata J, et al. Insight into the development of a new index, vesical adaptation response to diuresis, for understanding lower urinary tract dysfunction. Int J Urol. 19. doi: 10.1111/iju.14769, 2021