Chapter 19: Nocturia in Elderly Persons and Nocturnal Polyuria Dean A. Kujubu Department of Medicine, UCLA School of Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California Nocturia is defined by the International Conti- Conditions such as congestive heart failure, ne- nence Society as the interruption of sleep one or phrotic syndrome, autonomic neuropathy, and ve- more times at night to void.1 Although nocturia is nous insufficiency lead to interstitial edema forma- relatively uncommon among younger adults, by 80 tion during the day. Mobilization of the yr of age, the prevalence rises to 80 to 90% in both accumulated interstitial fluid while recumbent re- men and women.2 The presence of nocturia dis- sults in nocturia. Obstructive sleep apnea is associ- rupts sleep, leading to daytime somnolence, depres- ated with excessive atrial natriuretic peptide pro- sive symptoms, cognitive dysfunction, and a re- duction. Neurologic dieases, such as Alzheimer’s duced sense of well being and quality of life.3 disease and Parkinson’s disease, are associated with Moreover, nocturia is associated with an increased alterations in the diurnal secretory pattern of neu- risk morbidity and even mortality.4,5 rohormones, such as natriuretic peptides and anti- diuretic hormone. Patients with chronic kidney dis- ease are unable to maximally concentrate their PATHYPHYSIOLOGY urine and often must void at night. In many cases, the cause of nocturnal polyuria is Although it is commonly assumed that nocturia in undefined. In idiopathic nocturnal polyuria, As- the elderly is primarily a urologic problem, such plund and Aberg8 suggested that anti-diuretic hor- thinking is inaccurate. The pathophysiology of noc- mone (ADH) levels, which are typically elevated turia in the elderly involves the complex interplay of during sleep, are abnormally low in these individu- several factors.6 Age-related changes in the urinary als. This finding is not universally seen, however, system and in renal function occur. Sleep itself has particularly among women.9 Furthermore, a rela- effects on renal function. Sleeping patterns and tive nocturnal deficiency of ADH fails to explain the sleep architecture change with aging. Finally, dis- altered diurnal excretion patterns of sodium and ease states and medications may affect the urinary nonelectrolyte solutes that occur among these indi- system, sleep architecture, and renal function. viduals. In some individuals with nocturnal poly- Common causes of nocturia in the elderly are listed uria, diurnal variation in GFR is absent or even re- in Table 1. versed, such that creatinine and sodium excretion rates are higher at night than during the day.10 Some investigators suggest that these increases are associ- SYNDROME OF NOCTURNAL POLYURIA ated with higher night-time BP or the “nondip- ping” phenotype.11 Nocturnal polyuria is a syndrome where the usual day to night ratio of urine production is altered.7 In patients with nocturnal polyuria, Ͼ33% of the total daily urine output occurs at night, although the daily total urine output remains normal. A careful Correspondence: Dean A. Kujubu, Program Director, Nephrol- voiding diary, incorporating measurements of ogy Fellowship, Clinical Assistant Professor of Medicine, UCLA voided volumes, is essential to make the diagnosis. School of Medicine, Kaiser Permanente Los Angeles Medical Center, 4700 Sunset Boulevard, 2nd Floor, Los Angeles, CA Common causes of nocturnal polyuria are listed in 90027. E-mail: [email protected] Table 2. Copyright ᮊ 2009 by the American Society of Nephrology American Society of Nephrology Geriatric Nephrology Curriculum 1 Table 1. Common causes of nocturia in the elderly Table 3. Evaluation of nocturia in the elderly Bladder dysfunction History: including medications, comorbid conditions Bladder outlet obstruction (caused by, for example, benign Physical examination: orthostatic vital signs, complete exam prostatic hyperplasia) including abdominal and genitourinary exams Severe detrusor dysfunction/large residual urine volume Laboratory studies: electrolytes, calcium, renal function, glucose, Detrusor overactivity urinalysis Urinary tract infection Other studies: post void residual volume, urinary flow studies, Decreased functional bladder capacity voiding diary Bladder tumor or bladder stones Other studies to be considered: urine culture, polysomnogram, Pelvic floor laxity (caused by, for example, cystocoele, uterine 24-h ambulatory blood pressure monitor, urodynamic evaluation prolapse) Excessive nocturnal urine production deficits related to the sacral nerve roots, including sensory def- Edema-forming states (e.g., congestive heart failure, nephrosis) icits, poor sphincter tone, or absent anal wink reflex. Obstructive sleep apnea Initial laboratory testing should include assessment of renal Neurodegenerative conditions (e.g., Parkinson’s disease, function, blood glucose and electrolytes, serum calcium, and Alzheimer’s disease) Diabetes mellitus and diabetes insipidus urinalysis (incorporating microscopic examination of the Hypokalemia and hypercalcemia (causing nephrogenic diabetes urine). If symptoms suggest infection, a urine culture should insipidus) be obtained. Urinary flow rate and postvoid residual urine vol- Drugs (diuretics, calcium channel blockers, caffeine, alcohol, ume should also be assessed. The patient should be requested SSRI) to keep a careful voiding diary for 3 d. The volume and time of Chronic kidney disease each void, as well as whether or not the voiding episode dis- Autonomic neuropathy and venous stasis rupted sleep, should be noted. If bladder dysfunction or blad- Excessive fluid intake der outlet obstruction is suspected, detailed urodynamic eval- Idiopathic nocturnal polyuria (possibly caused by deficient uation may be indicated. A polysomnogram may be indicated nocturnal ADH secretion) if symptoms suggest obstructive sleep apnea. A 24-h ambula- tory BP recording can be considered to ascertain the presence EVALUATION of nondipping at night. The evaluation of a patient with nocturia is outlined in Table 3. A careful history and physical examination provide clues to the TREATMENT OF NOCTURIA IN THE ELDERLY etiology of nocturia. A weakened urinary stream, hesitancy, and a sense of incomplete voiding suggest bladder outlet ob- Treatment for nocturia in the elderly is outlined in Table 4. struction. Frequency, urgency, and bladder spasms suggest Simple maneuvers, such as reducing fluid intake for 6 h before bladder irritation, perhaps caused by infection. Gross hematu- recumbency, are usually not successful. Compression stock- ria might indicate a bladder tumor or stones. The presence of ings, phototherapy, and pelvic floor exercises can be tried. concurrent diseases and the use of medications such as diuret- Phototherapy is thought to reset the normal circadian rhythm ics, calcium channel blockers, and selective serotonin reuptake inhibitors (SSRIs), and habits such as excessive intake of fluids, Table 4. Treatment of nocturia in the elderly alcohol, and caffeine are also important to note. Nonpharmacologic On physical examination, orthostatic vital signs should be Reducing fluid intake 6 h before recumbency assessed. Evidence of edema-forming states, including venous Reduce caffeine and alcohol intake insufficiency, should be sought. Abdominal examination and a Dried fruit careful genitourinary examination should be performed to de- Compression stockings tect prostatic enlargement in men, pelvic floor laxity in Biofeedback, bladder/pelvic floor exercises Phototherapy women, bladder outlet obstruction—as manifest by a large Continuous positive airway pressure (for obstructive postvoid residual urine volume—or evidence of neurologic sleep apnea) Neuromodulation Table 2. Causes of the syndrome of nocturnal polyuria Pharmacologic Congestive heart failure Alpha adrenergic blockers, 5-␣-reductase inhibitors Obstructive sleep apnea Estrogen creams, hormone replacement Nephrotic syndrome Nonsteroidal anti-inflammatory agents Autonomic neuropathy Melatonin Chronic kidney disease Imipramine Venous insufficiency Anticholineric agents Neurologic diseases (Parkinson’s disease, Alzheimer’s disease) Loop diuretics Idiopathic Desmopressin 2 Geriatric Nephrology Curriculum American Society of Nephrology that is disrupted in patients with nocturia. Continuous positive • Voiding diaries are essential for diagnosis • airway pressure for obstructive sleep apnea improves nocturia Consider alternative diagnoses • Management of nocturia is frequently nonsurgical in anecdotal cases. • Several therapeutic options are available Double-blind, placebo-controlled studies have been per- formed examining various pharmacologic measures in the treatment of nocturia. Most of the studies are small and are of DISCLOSURES short-term duration. The administration of loop diuretics None. timed 6 to 10 h before recumbency, which induces a mildly hypovolemic state, can be tried but is usually not successful. REFERENCES The most extensive studies have been performed using desmo- pressin, a synthetic analog of anti-diuretic hormone. Multi- *Key References center, double-blind, placebo-controlled trials of oral desmo- 1. van Kerrebroeck P, Abrams P, Chaikin D, Donovan J, Fonda D, Jack- pressin in both men and women have shown a reduction in son S, Jennum P, Johnson T, Lose G, Mattiasson A, Robertson G, nocturnal voiding among patients with nocturnal polyuria Weiss J; Standardisation Sub-committee of the International Conti- nence Society: The standardisation