Platinum Priority – From Lab to ClinicEditorial by Marcus J. Drake on pp. 289–290 of this issueDiagnosing the Pathophysiologic Mechanisms of Nocturnal Polyuria
Introduction
Nocturnal polyuria (NP) is an important cause of nocturia in adults and nocturnal enuresis (NE) in children [1]. Results of extensive investigations into the pathophysiology of NE in children have led to individualized treatments with higher efficacy rates and lower side effects [2], [3]. In adults, NP is diagnosed based on a bladder diary, and treatment is more often based on trial and error than on evidence-based findings [4]. Extrapolation of pediatric data suggests that measurement of a 24-h concentration or renal function profile (RFP) for analysis of the nocturnal diuresis rate, concentrating capacity, and solute-conserving capacity could allow differentiation of NP pathophysiology as a guide to individualized treatment of adult patients with NP, as in children with NE [5].
In studies with limited participants, water diuresis and/or solute diuresis were identified as pathophysiologic mechanisms that play a role in adult NP [5]. Water diuresis is associated with impairment of vasopressin action, whereas solute diuresis can be due to increased atrial natriuretic peptide secretion, as seen in patients with obstructive sleep apnea and patients with heart failure [6]. Impaired circadian rhythms for these hormones also affect the circadian rhythms for renal clearance of free water and solutes. Healthy children exhibit marked circadian rhythms for hormones involved in urine production [7]. It is believed that a loss of these circadian rhythms in older patients is a physiologic aging effect. However, the consequences can be pathologic, for example when NP leads to bothersome nocturia affecting general health and sleep quality [8], [9]. In younger adults, circadian rhythms are assumed to be somewhere in between those of children and older individuals, but evidence is limited.
The aims of this study were:
- 1.
To map circadian rhythms for water and solute diuresis in populations with and without NP to establish a reference for normal circadian rhythms in an adult population;
- 2.
To evaluate the use of RFPs in the diagnostic approach to NP; and
- 3.
To evaluate the distribution of different pathophysiologic mechanisms of NP among patients.
Section snippets
Patient selection and data collection
A prospective observational study was designed and carried out in Ghent University Hospital, Belgium, between October 2011 and May 2013. Participants were recruited via posters, brochures, and consultations. There were no specific inclusion criteria. Exclusion criteria were neurogenic bladder and/or bladder/urethra surgery. On the basis of bladder diary results, participants were assigned to subgroups with or without NP. A modified International Continence Society (ICS) definition of NP was
Results
The results for 112 subjects were eligible for analysis; 77 with NP and 35 without NP. The mean age was 57 yr (SD 16 yr) and 41% of the participants were female. Significantly higher nocturnal voided volume (NVV; p < 0.001) and nighttime frequency (p < 0.006) were observed in the NP group (Table 1).
Discussion
NP can be considered a normal part of the aging process; it is known that loss of circadian rhythms for diuresis-regulating hormones and renal concentrating and sodium-conserving capacity occurs with advancing age [12], [13]. However, the NP population in the present study did not consist of only older people (age range 18–85 yr), indicating that this process had already started at a younger age in a considerable proportion of the study population.
Healthy children exhibit a pronounced circadian
Conclusion
NP is more than just an increase in overnight diuresis; it is a heterogeneous condition with two different underlying mechanisms: water diuresis and sodium diuresis. A large percentage of patients exhibit variable degrees of both characteristics.
RFP involving collection of eight urine samples over 24 h allows differentiation of the pathophysiologic mechanisms underlying NP and of the timing of high FWC or high sodium clearance during the night. Use of this test complements a bladder diary in
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