Clinicians are praising a recent study that provides insight into the pathophysiology of nocturnal polyuria (NP).

Donald L. Bliwise, PhD, a professor of neurology, psychiatry, and behavioral sciences at Emory University School of Medicine Sleep Center in Atlanta, Georgia, and who was not involved in the research, said the study is the first US-based prevalence study of NP that collected frequency volume diary data in a non-clinic population. “The authors should be congratulated wholeheartedly on that stunning achievement,” he said.

Dr Bliwise also observed, “NP with or without other factors is a common occurrence. Given the importance of nocturnal voiding and its links to morbidity and even mortality, further population-wide studies of NP in the US population should be pursued with vigor.”

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The Epidemiology of Nocturnal Polyuria (EpiNP) study, which was published in the Journal of Urology, demonstrated that NP is highly prevalent in both sexes in the United States, but it is much more common in women. Further, investigators observed that study participants who had nocturia but not NP had less nocturia than those who had both nocturia and NP due to much lower nocturnal urine production.

“Study findings may provide clues to nocturia treatment in emphasizing factors influencing urine production in comparison to factors influencing bladder capacity,” investigators J.L.H. Ruud Bosch, MD, of Franciscus G&V Hospital, Rotterdam, the Netherlands, and colleagues wrote. “As NP is prevalent in both sexes with clinically relevant nocturia, providers should address the causative, potentially serious underlying medical and urological pathophysiological conditions which contribute to NP.”

Treating by Cause

Nephrologist Dean A. Kujubu, MD, of Kaiser Permanente Los Angeles Medical Center Clinical and an associate professor at UCLA School of Medicine, agreed that the study is an important contribution to the field. “It points out that there is no uniformity on how exactly to define the entity and depending on the definition one uses, one gets different results,” he said. The underlying pathophysiology of NP still needs to be elucidated.

“My bias has been that NP is due to a dysregulated CNS diurnal cycle, though daytime peripheral fluid pooling and nocturnal central redistribution may also play a role,” said Dr Kujubu.

As a sleep researcher, Dr Bliwise noted that specific sleep disorders or general sleep fragmentation may be associated with increased nocturnal urine production, leading to nocturia. “As such, a greater focus on sleep disruption per se becomes a potentially attractive, but under-appreciated, target for treatment,” he said.

It is well established that nighttime voids can be a symptom of other conditions such as overactive bladder and benign prostatic hyperplasia. “Medications affecting bladder contractility are more appropriate for those with overactive bladder rather than NP per se,” Dr Kujubu said.

According to Dr Bliwise, anti-diuretic therapy remains “a strong option” for treating NP, but one not readily adopted by most practitioners for a wide variety of reasons, “most lining up on the side of safety rather than efficacy.”

Improved Pharmacologic Therapy

Urologist Benjamin Brucker, MD, of NYU Langone Health in New York, New York, said efforts to improve safety of drug therapy have led to appropriate dosage and pharmacokinetics of desmopressin, which is approved for NP. “The amount of drug needed for efficacy is much lower than what has traditionally been used,” Dr. Brucker said. He also noted that novel delivery systems, such as sublingual dissolving tablets, ensure quick onset. “Because of drug development that’s taken place in the last few years we have a much more robust dataset regarding safety when treating NP,” Dr Brucker said.

Dr Brucker said it may be best to consider NP as its own condition. “The mechanism that drives most nocturnal voids is the overproduction of urine in the kidney. That is why therapies that safely reduce the volume of urine produced at night are attractive to treat this condition.”

The EpiNP study included 4893 men and 5297 women aged 30 years and older who completed a baseline survey of lower urinary tract symptoms. The study included a subset of individuals who completed 3-day bladder diaries. The cohort was 75% White, 12% Black, 6% Asian, and 15% Hispanic or Latino. Investigators used 2 definitions of NP: a nocturnal polyuria index greater than 33% (NPI33) and a rate of nocturnal urine production greater than 90 mL/h (NUP90).

Higher Prevalence in Women

“Prevalence estimates were higher for all categories of NP using the NPI33 definition compared to NUP90 for both sexes, but the difference was considerably more pronounced among women, indicating a potential area of unmet need and future research,” the investigators wrote.

Using the bladder diary data, the investigators defined categories of NP: idiopathic NP and NP associated with overactive bladder (NPOAB), bladder outlet obstruction in men (NPBOO), and comorbidities in both sexes (NPCom).

Urine production (maximum nighttime volume, total volume, nocturnal urine production) was higher in both men and women with idiopathic NP and NPCom using both NP definitions compared with other NP groups. The median number of nighttime urinations was greatest for NPOAB and NPBOO in men, and NPOAB and NPCom in women. The bother associated with nighttime voiding varied among NP subgroups and was highest in NPBOO for men (NPI33: 69.6%; NUP90: 71.1%) and NPOAB for women (NPI33: 67.5%; NUP90: 66.0%).

In an accompanying editorial, Thomas F. Monaghan, MD, of the University of Texas Southwestern Medical Center in Dallas, commented, “Notwithstanding the direct commercial interests of the sponsoring/funding organizations in antidiuretic replacement therapy, this is a methodologically sound survey which amassed an unparalleled volume of voiding diary data, most importantly with purposeful inclusion of groups traditionally under-represented in research on this pervasive condition.”


Ruud Bosch JLH, Chapple CR, Mueller ER, et al. Differences in the prevalence of nocturnal polyuria in the US by definition: results from the epidemiology of nocturnal polyuria study. J Urol. doi:10.1097/JU.0000000000002500