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Chipping Away At Nocturia By Treating Sleep Apnea

A recent article by Kudlata et al from the Medical College of Georgia1 brings to mind the established but not very frequently discussed association of obstructive sleep apnea (OSA) with nocturia. In this report, the issue was looked at by conducting a retrospective chart review of 37 patients with nocturia (defined as 3 times or more) who had completed an at-home sleep study for OSA. Baseline not nocturia severity, defined as the average number of nocturnal voids, was recorded and severities at different times during the protocol, which consisted of recordings before treatment, after medical management, before continuous positive airway pressure (CPAP/APAP), and after medical management plus CPAP. All patients were men who met the diagnostic criteria for OSA. The mean nocturia severity, measured by the average number of nightly voids at the time of sleep study referral, was 5.5. Only a total of 16 of these patients initiated CPAP/APAP therapy. All 16 had started medical therapy with specific medications based on what was thought to be the underlying urologic cause for nocturia. These medications include an alpha blocker, alpha blocker plus phosphodiesterase inhibitor, alpha blocker plus 5A reductase inhibitor (all for BPH), anti-muscarinic therapy for overactive bladder, and DDAVP for nocturnal polyuria. Following the initiation of medical management, the severity of nocturia decreased from an average of 4.33 nocturnal voids per night to 3.44 nocturnal voids per night. With the introduction of specific therapy for OSA, the severity of nocturia was further reduced to 2.38 nocturnal voids per night. This latter reduction, but not the former, was statistically significant. There were no significant associations between nocturnal severity and age, BMI, or OSA severity. Follow up time from CPAP, and in this situation, the self-reported improvement varied between two and three months. Although this protocol did not specifically measure the effects of positive airway pressure therapy on nocturia, it nevertheless prompted the authors to suggest that there should be heightened suspicion for OSA in all newly diagnosed nocturia patients. They also pointed out that sleep evaluation and treatment is suboptimal in routine practice, which they ascribed to the excessive wait times associated with scheduling sleep studies and the fact that adherence to positive pressure airway therapy remains a challenge, with literature indicating that 46-83% of patients are non-adherent due to discomfort and other factors.

Functional urologists with a particular interest in nocturia wish to review the systematic analysis by Di Bello et al,2 which includes 62 well-chosen references and a focused evaluation of 38 studies selected from an initial search of 202 reports. These studies encompassed 19703 patients with nocturia. Pre- and postoperative outcomes following CPAP or surgical treatment for OSA were reported in 12 of the included studies, representing 713 patients. Several key observations from this review include:

  1. The frequency of nocturia increases along with OSA severity. Pathological nocturia in this review was defined as twice or more per night
  2. Generally, patients with OSA experience nocturia due to easy waking or increased bladder filling.
  3. The pathophysiological mechanisms connecting OSA and nocturia are not completely understood, but are summarized as follows. The hallmarks of OSA are intermittent hypoxia (IH) or periodic exposure to reduced blood oxygen. As a result, there is sleep fractionation with breathing pauses, which themselves could result in the arousal of patients, and this arousal could determine the need of patients to urinate. The IH caused by the obstruction to air flow results in the reduction of intrathoracic pressure, and consequently, the pressure gradient increases the venous return to the right atrium, which expands. At the same time, the IH activates the sympathetic nervous system, leading to vasoconstriction and increasing blood pressure. The vasoconstriction of pulmonary arteries continues to increase the level of hypoxemia. The atrial dilation results in an increased secretion of atrial natriuretic peptide (ANP) that stimulates the excretion of sodium and, thus, water excretion from the kidneys. These effects are implemented by brain natriuretic peptide (BNP), which is secreted in response to central nervous system hypoxemia and hypercapnia. Both ANP and BNP inhibit the secretion of anti-diuretic hormone, which results in salt excretion and nocturnal polyuria.
  4. Results were collected relative to the effect on nocturia of CPAP, which the authors feel should be first line treatment for OSA patients without tonsil or adenoid enlargement, nasal polyps or facial deformities. With CPAP, a continuous stream of positive pressure air keeps the airway open, and breathing is not impeded. For patients who are intolerant of or who are not candidates for CPAP, there are surgical options, which include removing any obstruction, repositioning or reducing the tongue, or, most recently, implantation of a device that stimulates the hypoglossal nerve, which innervates the tongue and prevents it from blocking the airway.
  5. The authors note that less than one third of the papers included assessed the results of CPAP on nocturia. The average reduction in frequency was 50%. It should be noted, however, that none of the reports in which nocturia frequency and urine volume were noted included patients with nocturia three times or more, few had additional information regarding concomitant medication, and follow up was relatively short. In other words, patients noted in the reviewed reports were patients for whom the initial presenting complaint was OSA and not nocturia.
A more detailed discussion of the pathophysiology linking OSA and nocturia is provided in the review by Vrooman et al,3 However, similar to other reports in the literature, it contains limited data specifically addressing the effects of CPAP on patients with nocturia occurring three or more times per night.

Two additional articles are worth noting. One is a report by a group of authors from Mexico,4 citing retrospective data from a group of men with what was termed severe OSA who underwent CPAP (51 patients) or deobstruction surgery (46 patients). The reported results demonstrated marked reductions in nocturia frequency. In the CPAP group, nocturia events decreased from 4.53 ± 1.03 to 0.51 ± 0.61. In the deobstruction group, events decreased from 3.78 ± 0.84 to 0.70 ± 0.60. No follow up data beyond 3 months (for CPAP) were recorded. Another group from Turkey5 reported less spectacular results with CPAP and surgery, but in a series of patients with various degrees of OSA and lesser frequencies of nocturia. For the whole group, nocturia decreases from 2.3+/- 1.4 times to 1.7+/- 2.2. They did not report the results for each group separately, but concluded similarly that there was no difference in the results between the two groups.

The association between OSA and nocturia remains a fascinating one with many questions still unanswered. Some of these are: Although there is a general description of pathophysiology that is accepted by most, some details of the hormonal and receptor ramifications still need to be clarified; the statistical associations between patients presenting with various degrees of nocturnal frequency at various ages and with various comorbidities, with OSA need to be delineated, and the ideal treatment for OSA in those who do not tolerate or fail CPAP needs to be better delineated with respect to effects on nocturia.

Written by: Alan Wein, MD, PhD, FACS, Professor of Clinical Urology, Department of Urology, Desai Sethi Urology Institute (DSUI), University of Miami Miller School of Medicine, University of Miami Health Systems, Miami, FL

References:

  1. Kudlata, FP et al, Improving nocturia management through sleep apnea diagnosis and treatment. Neurourology and Urodynamics 2026; 45: 385-389
  2. Di Bello, F et al. Nocturia and obstructive sleep apnea syndrome: a systematic review. Sleep Medicine Reviews 2023; 69 101178, https://doi.org/10.1016/j.smrv.2023.101787
  3. Vrooman,OPJ et al Nocturia and obstructive sleep apnoea. Nature Reviews Urology 2024; 21: 735-753
  4. Labra, A. Nocturia as a clinical indicator of severe obstructive sleep apnea syndrome and its response to cpap or surgical treatment. Sleep Science 2022; 15: 383-387
  5. Deger,M et al. Comparison of the effect of continuous positive airway pressure and surgical treatment of obstructive sleep apnea syndrome on nocturia. J Urol Surg 2021; 8: 106-110