PARIS _ Nocturia, outside the classic urological spectrum of benign prostatic hypertrophy, can be explained by subvesical obstruction, overactive bladder and/or nocturnal polyuria. Focus on the latter, with the Dr François Hervéurologist (department of urology, Ghent University Hospital, Belgium), spoke on this subject at 118th congress of the French Association of Urology (CFU; 20-23 November 2024) [1].
Nocturia is characterized by waking up during the main period of sleep to urinate. This latest definition published in 2019 makes it possible to include patients working at night [2].
Nocturia goes far beyond the bladder and prostate and its origin is frequently multidisciplinary.
For example, cardiologists frequently encounter this symptom in patients with diabetes or heart failure, lower limb edema, etc.
Sleep specialists often identify nocturia in patients with obstructive sleep apnea syndrome. Likewise, gynecologists observe it in menopausal patients, or even endocrinologists in certain metabolic pathologies.
Nocturia often results from a combination of problems, requiring a complete assessment to adapt the treatment to each patient.
Dr François Hervé
The impacts of nocturia go beyond the discomfort and repercussions on the quality of life of the person concerned and the person sleeping with them, also affecting morbidity and mortality.
Already, the risk of nocturnal falls exists. Furthermore, in the long term, nocturia is associated with an increase in cardiovascular risk, including an increased risk of sudden death. Indeed, the first nighttime awakening frequently occurs in the first two to three hours of sleep and this period corresponds to deep sleep, essential for physical and mental regeneration.
One study showed that shorter time to first urination was associated with poorer sleep quality, shorter sleep duration, poorer sleep efficiency, and greater daytime dysfunction. [3]. Studies in animal models have found that deprivation and impairment of deep sleep can lead to glucose intolerance, thereby increasing the risks of diabetes and other metabolic pathologies.
Often associated with nocturnal polyuria
Nocturia is classically described as a symptom linked to the bladder filling phase, and therefore not exclusively involving the prostate. “Interest has recently broadened to other factors, such as overactive bladder,” emphasizes Dr. Hervé. But in the urinary system, we must not forget the kidneys, and several international studies show that nocturnal polyuria is common in patients with nocturia. In reality, the number of patients presenting nocturia without nocturnal polyuria remains relatively low. »
This high prevalence of nocturnal polyuria in patients with nocturia has been found in several international studies. In the United States, only 12% of patients with nocturia did not have nocturnal polyuria [4]. In Japan, this figure was 17%. [5]while a European study estimated it at 26% [6].
Three main mechanisms can explain nocturia
The first mechanism is low bladder capacity, which may result from overactive bladder or subvesical obstruction.
The second mechanism is global polyuria, corresponding to excessive urine production throughout the day (>40mL/kg/24h).
Finally, the third mechanism is nocturnal polyuria, characterized by an abnormally high proportion of urinary production during the night (>33% 24hUP) [7,8] . It is defined by calculating the nocturnal polyuria index (NPI), a simple and inexpensive way to make the diagnosis. This is obtained by dividing the volume of urine produced during the night (recovered with the first urination in the morning) by the total volume urinated over 24 hours. If this index exceeds 33%, that is to say if more than a third of daily urinary production is produced during the night, we then speak of nocturnal polyuria.
“Our team conducted a study including 80 patients to refine the diagnosis of nocturia and its mechanisms.[9]explains Dr François Hervé. These patients followed a strict protocol of waking up every three hours to provide a urine sample and blood draw. This monitoring allowed us to evaluate diuresis throughout the day and night.
In a normal patient, without nocturnal polyuria, a reduction in diuresis is observed during the night. On the other hand, in patients with nocturnal polyuria, nocturnal diuresis increases significantly. We have thus identified four profiles of nocturnal polyuria: a mixed profile, found in nearly 50% of cases, a profile only “free water” with aqueous diuresis during the night (20%), a profile only sodium (“sodium diuresis”). » nocturnal; 20%), and an indeterminate profile in approximately 10% of cases. »
Nocturnal polyuria may be attributed to water or sodium diuresis, or a combination of both. Measuring the renal function profile during first-line screening for nocturnal polyuria to discriminate between water and solute diuresis as pathophysiological mechanisms complements the voiding calendar and could facilitate optimal and individualized treatment of patients. However, it is not a question of recommending in current practice a complex protocol such as waking up every three hours to precisely define each type of nocturia.
Treating nocturia often means treating nocturnal polyuria
Nocturia remains a little-known, even neglected, subject. Patients wait on average two years between the first consultation and the prescription of an effective treatment [10]. “This delay is partly explained by the historical belief that the prostate is the main cause, while other mechanisms, such as overactive bladder and nocturnal polyuria, are still underestimated, although this trend is gradually changing,” estimates the urologist.
In terms of treatment, behavioral modifications can be proposed (dietary intake – particularly regarding foods rich in water or even the cooking methods of vegetables – and drinking habits; urinating before going to bed, avoiding diuretics in the evening), followed by drug treatments.
Namely, for measures such as wearing compression stockings, elevating the legs, engaging in physical activity, losing weight, using sleeping pills, following a diet with salt and protein restriction, there is a lack of studies and the level of recommendation is low.
On the medication side, the two treatments benefiting from the highest level of scientific proof are desmopressin and continuous positive airway pressure for obstructive sleep apnea.
Desmopressin, in particular, is the reference treatment when it comes to treating nocturnal polyuria, regardless of aqueous or sodium diuresis profiles. This treatment works by increasing the reabsorption of free water, thereby reducing nighttime urine volume. However, its use requires special attention, particularly in patients aged over 60-65 years, mainly due to the risk of hyponatremia.
Desmopressin is a synthetic analogue of antidiuretic hormone (ADH) that increases free water reabsorption, reduces diuresis, and increases urine concentration. Women are more sensitive to desmopressin because this molecule binds to kidney V2 receptors (the V2 receptor gene is located on the X chromosome). In them, a higher response rate is therefore observed with a lower dose.
Specifically, regarding the side effects of desmopressin, hyponatremia (< 130 mmol/L) occurs in 5% of patients, 50% of whom are asymptomatic. This hyponatremia is caused by water retention due to the antidiuretic effect, combined with the consumption of beverages. To avoid this risk, it is recommended to restrict beverage consumption and administer the appropriate dosage.
“The key message is that nocturia often results from a combination of problems, requiring a complete assessment to adapt the treatment to each patient,” summarizes Dr François Hervé. The voiding calendar is a valuable tool for collecting information on bladder capacity and identifying a possible low capacity or overactive bladder. Concerning the therapeutic options, a dual therapy combining desmopressin and anticholinergics can be considered, but its implementation must be considered according to the characteristics of the patient. For example, in a patient also presenting daytime symptoms linked to an overactive bladder, it could be wise to start with a treatment targeting these symptoms (such as an anticholinergic, or even a specific beta-3 adrenergic receptor agonist), before introducing desmopressin to treat nocturnal polyuria. »
In elderly or frail patients, the choice of treatments must be particularly careful, taking into account the risk of adverse effects. The use of an anticholinergic may be problematic due to its potential impact on cognitive functions, particularly in the elderly. In this context, desmopressin, used alone or in combination, can be an interesting alternative, taking the necessary precautions.
Links of interest of experts: Not declared
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