Nocturia, the most bothersome lower urinary tract symptom is a multifactorial condition and is associated with many underlying causes and contributing factors. Among them, Nocturnal Polyuria (NP) is a frequent contributor and is often overlooked. It is therefore essential to accurately diagnose the type of nocturia and the associated medical conditions for better treatment outcomes. This original article compares the pattern of diuresis at different circadian phases between men with Nocturnal Polyuria Syndrome (NPS) and secondary Nocturnal Polyuria using a three-day bladder diary.

Retrospective analysis of the three-day bladder diary of men with nocturia ( ≥ 1 nocturnal void) and NP (defined as Nocturnal Polyuria Index, NPi > 33% for men > 65 years and NPi > 20 for young men ) who presented in urology clinic from August 2020 to March 2021 were studied (1). Patients with urinary tract infections and neurogenic lower urinary tract symptoms were excluded from the study. Patients with NP and Chronic Kidney Disease (CKD), Congestive Cardiac Failure (CCF), Obstructive Sleep Apnoea (OSA), uncontrolled Diabetes Mellitus (DM), peripheral edema of unevaluated causes were classified as secondary NP. Patients without these conditions and not on loop diuretics were classified as NPS. The volume and timing of nocturnal and diurnal voids from bladder diary were used to derive Initial Sleep Diuresis Rate, ISDR (urine production rate from sleep onset to first nocturnal awakening), Middle Sleep Diuresis Rate, MSDR (urine production rate from first nocturnal awakening to last nocturnal awakening), Terminal Sleep Diuresis Rate, TSDR (urine production rate from last nocturnal awakening to first morning void), and Diurnal Diuresis Rate, DDR (daytime urine production rate), all expressed in ml/hour. Matching was done for evening fluid intake and evening caffeine intake between men with NPS and secondary NP. The odds of having a peak initial sleep diuresis rate (ISDR > MSDR and TSDR) was compared between patients with NPS and secondary NP using both univariate and multivariate logistic regression. The difference in MSDR and TSDR in both patient categories were analysed using Wilcoxon signed ranks test.

The study was completed in 83 patients with 48 patients having NPS and 35 patients having secondary NP ( CKD, n=18; CCF, n=7; OSA , n=3; uncontrolled DM, n=4; edema of unevaluated causes, n=5 ). There was no statistically significant difference in the mean age (62.52 ± 7.60 vs 64.24 ± 9.31; p =0.364 ), body mass index (22.62 ± 4.55 vs 23.74 ± 3.00; p =0.226) and daily fractions of evening fluid intake (0.30±0.11 vs 0.31±0.11; p=0.867 ) between men with NPS and secondary NP. Patients with NPS had a median (interquartile range) DDR, ISDR, MSDR and TSDR of 69.20 ml/hr (58.31 – 100.28), 111.03 ml/hr (70.68 – 158.43), 103.09 ml/hr (86.96 – 139.35) and 74.01ml/hr (44.86 – 109.62) respectively. However,  patients with secondary NP had a DDR, ISDR, MSDR and TSDR of 69.73 ml/hr (61.24 – 107), 94.93 ml/hr (58.95 – 157.56), 139.66 ml/hr (100 – 186.04) and 119.76 ml/hr (73.50 – 227.46) respectively. Patients with NPS had 5.3 times higher odds of having peak initial sleep diuresis rate (ISDR > MSDR and TSDR) when compared with patients having secondary NP, Chi-square (1, n = 83) = 10.59, p = 0.001. Patients with Nocturnal Polyuria Syndrome had a statistically significantly higher MSDR than TSDR, (Z= - 2.54, p = 0.01). In patients with secondary nocturnal polyuria, there was no statistically significant difference between middle sleep and terminal sleep diuresis rates,( Z = -0.43, p = 0.66). In the full multivariate analysis accounting for peak ISDR, hypertension and DM, peak ISDR ( OR, 4.09, 95% CI 1.33 – 12.62,p =0.014) and hypertension (OR, 0.21, 95% CI 0.07 – 0.66, p=0.007) remained statistically significant (Figure 2). The nocturnal diuresis pattern was further investigated in secondary NP patients. Patients with CKD, CCF, OSA and pedal edema of unevaluated causes, demonstrated an ebb phase in the initial nocturnal diuresis rate. Patients with uncontrolled diabetes mellitus showed a diuresis profile similar to patients with NPS, with an initial surge in nocturnal diuresis rate ( Figure1).

Men with NPS and secondary NP differ significantly in their diuresis pattern (2). Men with NPS have a peak diuresis rate in their initial sleep which gradually decreases towards the terminal sleep period. Men with secondary NP have an ebb phase in their initial sleep period which surges as sleep progresses. However, in them, the difference between MSDR and TSDR was not statistically significant. This difference in the pattern of diuresis rates can be attributed to the pathophysiological mechanisms involved in each category. NP of cardiogenic and renal etiologies are associated with sodium predominant diuresis and NPS is associated with free water predominant diuresis. Patients with NP secondary to uncontrolled DM show a pattern similar to NPS. This can be explained by the combined effect of DM on the neurophysiology of the lower urinary tract in addition to the solute predominant diuresis. However further studies on the diuresis pattern in DM patients with larger sample size is warranted.

In the various etiologies of NP, interventions vary as per the different underlying mechanisms. Bladder diary is a simple, effective and vital tool in the categorisation of NP patients and in the formulation of individualized treatment plans. A better understanding of the oscillations in the nocturnal diuresis rate in NP patients can improve treatment outcomes by optimizing the timing and half-life of antidiuretic medications.

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Monaghan TF, Suss NR, Epstein MR, Flores VX, Wu ZD, Michelson KP, Hervé F, Bliwise DL, Everaert K, Weiss JP. Differential Nocturnal Diuresis Rates Among Patients with and Without Nocturnal Polyuria Syndrome. Eur Urol Focus. 2020 Mar 15;6(2):320-326. doi: 10.1016/j.euf.2018.10.015. Epub 2018 Nov 2. PMID: 30392866.