Hypothesis / aims of study
The safety and efficacy of low-dose desmopressin have been reported in the randomized controlled trials (Ref. 1), but these trials had a short observation period of 3 months and included patients with an average age of 60-63 years, which significantly differs from the age range of patients with nocturnal polyuria in the real world (average age 77-79 years) (Ref. 2). Therefore, this study prospectively examined the safety and efficacy of low-dose desmopressin in treating male nocturnal polyuria over a period of one year.
Study design, materials and methods
Between January 2020 and July 2022, the Japanese male patients with nocturnal polyuria for whom behavioural therapy was ineffective were started on desmopressin at a dose of 25µg. After 1 week, if there was a lack of efficacy and no adverse events were observed, the dose was increased to 50µg. If inefficacy or adverse events were observed, the administration was stopped. Before the treatment, weight, body mass index (BMI), fluid intake, salt intake, BNP, eGFR, and serum sodium levels were measured. After 1, 3, 6, 9 and 12 months of administration, weight and serum sodium levels were measured, and adverse events were checked to assess its safety. In addition, a 2-day frequency volume chart was performed after 1 and 12 months of administration to evaluate its efficacy.
Results
Forty male patients were enrolled in this study, including 16 cases aged over 80 and 24 cases under 80. The group aged over 80 showed significantly lower weight and BMI (20.8kg/m2 vs 23.7kg/m2) compared to the under 80 group, but there were no significant differences in fluid intake, salt intake, BNP, eGFR, and pre-treatment serum sodium levels. There was no significant difference in the dosage of low-dose desmopressin between the two groups. In the over 80 group, 6 cases discontinued medication due to hyponatremia-related events, in which hyponatremia were most common (5 cases), while in the under 80 group, 7 cases discontinued, with hyponatremia being most common (4 cases), but there was no significant difference in the incidence rate of hyponatremia-related events between the two groups. The adherence rate of medication over one year was 62.5% for those over 80 and 70.8% for those under 80, with no significant difference between the two groups (Fig. 1A). Regarding the onset timing of hyponatremia, in the over 80 group, 4 out of 5 cases occurred within 1 week of administration, while in the under 80 group, hyponatremia was observed after 1 month (2 cases), 6 months (1 case), and 12 months (1 case) (Fig.1B). The efficacy of low-dose desmopressin showed a significant improvement compared to baseline that persisted until one year in both groups (Fig. 2).
Interpretation of results
Although the number of cases was small, this study appears to be the first to prospectively examine the safety and efficacy of low-dose desmopressin for male nocturnal polyuria in patients aged over 80 for one year. Compared to the under 80 group, the over 80 group had a one-year medication adherence rate of 62.5% vs 70.8%, and the most common reason for discontinuation was hyponatremia-related events at 31.3% vs 16.6%, but there was no significant difference between the two groups, respectively. On the other hand, in the over 80 group, 4 out of 5 cases (80%) developed hyponatremia within 1 week and stopped the medication. As causes for hyponatremia due to desmopressin, age, eGFR, pre-treatment serum sodium levels and the dosage of desmopressin have previously been reported (Ref. 3). In addition, the study suggests that a BMI lower than 22 kg/m2 (appropriate weight) is a cause of hyponatremia.