Nocturnal polyuria is the most common cause of nocturia, accounting for 67% to 88% of all nocturia cases. Nocturia is not only a troublesome symptom that affects quality of life but also a risk factor for depression and death. Treating nocturia may improve the quality of life in older people and reduce the risk of depression and death. However, no fundamental treatment against nocturnal polyuria has been established because the pathogenesis of nocturnal polyuria is complex and not well understood. Previously, we have reported that combination of decreased nitric oxide (NO) production and excessive salt intake induces nocturnal polyuria in mice (1). The same mechanism may cause nocturnal polyuria in humans. The abdominal aortic calcification is associated with decreased vascular endothelial function and decreased NO production from arterial endothelium. The abdominal aortic calcification is also associated with higher risk for cardiovascular events such as stroke, myocardial infarction, and heart failure (2). Therefore, we hypothesized that abdominal aortic calcification may predict salt-induced nocturnal polyuria in humans. The aim of this study was to evaluate the predictive value of abdominal aortic calcification for salt-induced nocturnal polyuria in humans.

Living kidney transplantation donors between June 2019 and October 2020 were included. The abdominal aortic calcification was evaluated by abdominal aortic calcification index (ACI) (2). All patients were scanned using non-contrast computed tomography (CT) scans with a 5-mm slice thickness before surgery. Calcification was determined if an area of >1mm2 displayed a density of >130 Hounsfield units. The cross-section of the abdominal aorta on each slice was radially divided into 12 segments. The ACI was calculated as follows: ACI = (total score for calcification on all slices)/12 x 1/ (number of slices) x 100%. The patients were classified into two groups, high ACI and low ACI group, according to the ACI index. All patients were admitted to our hospital 2-4 days before surgery. Twelve-hour urine collection tests were performed 2 days before surgery, and urine collected from 10:00 to 22:00 h was defined as daytime urine, and urine from 22:00 to 10:00 h as nighttime urine. The daytime and nighttime urine volume, urinary salt excretion, and urinary nitric oxides (NOx) excretion were evaluated. The nighttime urine volume rate was defined as nighttime urine volume/daily urine volume. The urinary salt excretion was regarded as salt intake. First, to evaluate the impact of abdominal aortic calcification on NO production, the NOx excretion level was compared between high ACI and low ACI group. Next, to evaluate the predictive value of abdominal aortic calcification for salt-induced nocturnal polyuria, the correlation between salt intake and nighttime urine volume rate was compared between the two groups.
This study was performed in line with principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of our institute (No. 18418). Informed consent to participate in this study was obtained from all individual participants.

A total of twenty-seven living kidney transplantation donors were included. The age was 61 years (42-79), BMI was 23.8 kg/m2 (18.0-27.8), nighttime urine volume rate was 37.8% (16.4-65.2), salt intake was 6.6 g (2.8-15.4), NOx excretion was 203 umol/day (21-481), and ACI was 3.3 (0-27.4) (all values are median and (range)). Patients were divided into two groups according to the ACI as follows: low ACI, ACI<3.5%; high ACI, ACI>3.5%. Figure 1 (table) shows the characteristics of the patients. The NOx excretion level in low ACI group was significantly higher than that of high ACI group (212 (109-481) vs. 150 (21.0-314), P = 0.05). There was no significant difference in nighttime urine volume rate between the two groups (0.36 (0.16-0.65) vs. 0.43 (0.16-0.59), P = 0.67). Figure 2 shows the relationship between salt intake and nighttime urine volume rate in low ACI and high ACI group. The nighttime urine volume rate was positively correlated with salt intake in the high ACI group (R = 0.40, P = 0.03), but not in low ACI group (R = -0.07, P = 0.34).

In this study, we found that increased abdominal aortic calcification is associated with decreased NO production. Moreover, the relationship between excessive salt intake and nocturnal polyuria is significant in high ACI group, but not in low ACI group. These findings suggest that increased abdominal aortic calcification is involved in the mechanisms of salt-induced nocturnal polyuria in humans. Previously, we have reported that decreased salt excretion in daytime is the cause of nocturnal polyuria (3). Therefore, the endothelial dysfunction is considered to decrease salt excretion in daytime and cause salt-induced nocturnal polyuria.

The relationship between excessive salt intake and nocturnal polyuria is significant in high ACI patients. The high ACI level predicts salt-induced nocturnal polyuria in humans.

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Continence 7S1 (2023) 100973
DOI: 10.1016/j.cont.2023.100973