Recent research has shown that nocturnal polyuria (NP) is a heterogeneous condition that may be driven by excess nocturnal free water and/or sodium clearance. Consistently, behavioral and pharmacologic interventions targeting both nocturnal free water and sodium production have garnered considerable traction in the management of nocturia owing to NP. Relatively less attention has been afforded to urea—the most abundant urinary solute—despite the fact that urinary urea excretion is known to be highly interrelated with dietary protein intake [1]. Mechanistically, the body maintains a low concentration level of urea in both plasma and extracellular fluid, which lends to a daily urea excretion approximately two times greater the total body urea pool (and thus proportionally far greater than sodium, wherein daily excretion reflects approximately one-fifteenth of the total body sodium pool) [1]. Accordingly, it stands to reason that excretion of a large quantity of urea, as would be expected in patients following significant dietary protein intake, may reflect an additional important mediator in the pathogenesis of NP. This study aims to explore the association between NP and estimated dietary protein intake.

Post hoc analysis of prospective observational data from 170 adults who completed a renal function profile between October 2011 and February 2015. Each subject underwent a 24-h urine collection which included 8 urine samples collected at 3-h intervals (daytime: 10h-13h-16h-19h-22h and nighttime: 01h-04h-07h). Urine volume, osmolality, and urea were used to calculate urinary excretion of urea (urine urea x urine volume). Urinary urea excretion was subsequently employed to estimate dietary protein intake ([24-h urinary urea nitrogen excretion (UUN; g/day)] + 0.031 * [body weight (kg)]* 6.25) [2]. 
Patients were compared by NP status using two distinct cutoffs for NP in accordance with current International Continence Society terminology: 1) nocturnal urine production >90ml/h (NUP90) and 2) nocturnal polyuria index (nocturnal urine volume/24-h total urine volume) >0.33 (NPi33) [3].  	
Clinical and biochemical parameters were compared using the chi-square test and Mann-Whitney U test for categorical and continuous variables, respectively. A p-value <0.05 was deemed statistically significant. All continuous measures are reported as median (interquartile range).

A total of 170 adults were eligible for analysis (62% female, median age 66 [51-72] years), of whom 81 (47.6%) met the threshold for NP at NUP90, and 118 (69%) met the cutoff for NP at NPi33 (Table 1).
At NUP90, nighttime urea excretion higher in the NP vs. no NP group, which corresponded to a significantly higher estimated evening protein intake in subjects with NP (Table 2). No significant differences were observed in daytime urea excretion, estimated daytime protein intake, 24-h urea excretion, or estimated 24-h protein intake. 
At NPi33, nighttime urea excretion and estimated evening protein intake were likewise both significantly higher in the NP group. Among subjects with NP, daytime urea excretion and estimated daytime protein intake were significantly lower compared to the non-NP subgroup, and no significant differences were observed in 24-h urea excretion or estimated 24-h protein intake between groups.

A large protein-rich meal, as reflected in the urinary urea-based estimate of dietary protein intake, lends to a period of glomerular hyperfiltration and excess urine volume. In the present analysis, an increase in nocturnal urea excretion was observed specifically during the nighttime in subjects with NP, and no such trend was seen in subjects without NP. Estimated evening dietary protein intake was correspondingly significantly higher amongst the NP subgroup, as would be consistent with a large, protein-rich evening meal, and this finding persisted across two distinct accepted cutoffs for NP. Protein intake in the hours leading to sleep may reflect an additional important mediator in nocturia owing to excess nocturnal urine production.

Reduction of evening protein consumption may be an effective lifestyle intervention in the management of nocturia owing to NP. Future research on the association between NP and diet is warranted.

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Hashim H, Blanker MH, Drake MJ, et al. International Continence Society (ICS) report on the terminology for nocturia and nocturnal lower urinary tract function. Neurourol Urodyn. 2019;38(2):499-508.