A decrease in renal function is considered to be one of the causes of nocturnal polyuria. However, no studies have proved a causal relationship between renal dysfunction and nocturnal polyuria or determined its mechanism, and the exact causal relationship and mechanism are not well understood. In this study, we aimed to examine the mechanism of nocturnal polyuria in renal dysfunction by prospectively investigating the changes in daytime and nighttime urine volume, urine osmolality and urine osmolytes excretion before and after nephrectomy in the same individuals. Identification of the mechanism of nocturnal polyuria is expected to lead to establishment of a treatment strategy for nocturnal polyuria and nocturia.

We included patients who underwent laparoscopic nephrectomy at our hospital from June 2019 to October 2020. Blood and urine collection tests were prospectively performed 2 days before ant 7 days after nephrectomy to investigate the changes in renal function and daytime and nighttime urine volume, urine osmolality and osmolytes (i.e. sodium, potassium, and urea) excretion. Renal function was assessed using the estimated glomerular filtration rate (eGFR). Twelve-hour urine collection tests were performed, 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. Urinary sodium (UNa), potassium (UK), urea nitrogen (UUN), and creatinine (UCr) were measured in each period. The nighttime urine volume rate was defined as nighttime urine volume/daily urine volume. The nighttime Na excretion rate was defined as nighttime Na excretion/daily Na excretion. Fractional excretion of sodium (FENa) was calculated using the following formula: FENa(%) = (UNa/serum Na)/(UCr/serum Cr) x 100. The significance of differences between preoperative and postoperative data was tested using the paired t-test. Multiple linear regression analysis was performed to identify independent variables to determine the increase in the nighttime urine volume rate. The significance of difference between the change in rate of the eGFR (decrease) and daytime FENa (increase) was tested using Wilcoxon signed rank test.

There were 49 participants in this study. The eGFR was significantly decreased from 73.3 ± 2.0 to 47.2 ± 1.6 mL/min/1.73m2 (P < 0.01), and the nighttime urine volume rate was significantly increased from 40.6% ± 2.0% to 45.3% ± 1.5% (P = 0.04) with nephrectomy. Nephrectomy significantly decreased daytime urine osmolality (from 300 ± 22 to 195 ± 12 mOsm/kg, P < 0.01) and nighttime urine osmolality (from 273 ± 15 to 212 ± 10 mOsm/kg, P < 0.01). Nephrectomy also significantly increased the nighttime Na excretion rate (from 38.7% ± 2.1% to 48.8% ± 1.7%, P < 0.01), the nighttime K excretion rate (from 35.5% ± 1.7% to 46.5% ± 1.4%, P < 0.01), and the nighttime urea excretion rate (from 41.3% ± 1.8% to 47.4% ± 1.1%, P < 0.01). To identify the factors strongly associated with an increased nighttime urine volume rate with impaired renal function, we conducted multiple linear regression analysis. This analysis showed that age, a change in nighttime urine osmolality, and a change in the nighttime Na excretion rate were significantly associated with the nighttime urine volume rate (all P < 0.01). Of these factors, a change in the nighttime Na excretion rate had the highest standard partial regression coefficient (Fig. 1). To investigate the causes of the increase in the nighttime Na excretion rate, we compared changes in the eGFR and FENa with nephrectomy. Nephrectomy significantly increased daytime FENa (from 0.83% ± 0.04% to 1.03% ± 0.05%, P < 0.01) and nighttime FENa (from 0.66% ± 0.05% to 1.07% ± 0.06%, P < 0.01). However, the rate of increase in daytime FENa was significantly lower than the rate of decrease in the eGFR (P = 0.03) (Fig. 2).

The results mentioned above indicate that impaired renal function increases the nighttime urine volume rate. The results also indicate that impaired renal function decreases the nighttime urine osmolality and increases the nighttime urine osmolytes (Na, K, urea) excretion rate. Multiple linear regression analysis revealed that the increase in nighttime Na excretion rate has the strongest effect on the increase in nighttime urine volume rate. Furthermore, we found that the rate of increase in daytime FENa was significantly lower than the rate of decrease in the eGFR. This insufficient increase in daytime FENa compared with a decrease in the eGFR may be the cause of the increase in nighttime Na excretion. Our findings suggest that the main cause of the increase in the nighttime urine volume rate in renal dysfunction is carryover of Na excretion to the nighttime.

The increase in the nighttime Na excretion rate was found to have the strong effect on the increase in the nighttime urine volume rate, suggesting that decreased renal function increases the nighttime urine volume rate by carryover of Na excretion to the nighttime.