Nocturnal Polyuria

Nocturnal polyuria is the production of an excessive proportion of the 24 hour urine volume at night: nocturnal urine volume above 33 percent of the 24 hour total in adults over 65 years (above 20 percent in those under 35 years, and about 25 to 33 percent between). It is the commonest cause of nocturia in older people, accounting for about half to two thirds of cases, and it can coexist with reduced bladder capacity.

• Mechanisms:
  • Loss of the normal circadian rise in antidiuretic hormone at night, which lowers night time free water reabsorption.
  • Mobilisation of dependent oedema when lying flat: heart failure, venous insufficiency, nephrotic syndrome, calcium channel blockers (amlodipine), pregnancy, hypoalbuminaemia, lymphoedema.
  • Obstructive sleep apnoea: increased atrial natriuretic peptide secretion from negative intrathoracic pressure.
  • Diabetes mellitus with glycosuria, hypercalcaemia, chronic kidney disease (loss of concentrating ability), nocturnal hypertension, and evening drinking of fluids, alcohol and caffeine.
  • Drugs: diuretics given late, lithium, SGLT2 inhibitors, demeclocycline.
• Differentiate from global polyuria (24 hour volume above 40 mL/kg or 2.8 L): diabetes insipidus, primary polydipsia, uncontrolled diabetes, hypercalcaemia.
• Complications: sleep fragmentation, daytime fatigue, falls and hip fracture, depression, cognitive impairment, and a higher mortality.

• Waking to void large volumes more than once a night; sleep afterwards is usually possible; daytime frequency may be normal.
• Ask about thirst, evening fluids, tea, coffee, alcohol, diuretic timing, snoring, apnoea, daytime sleepiness, ankle swelling, orthopnoea, paroxysmal nocturnal dyspnoea, weight changes, dyspnoea, symptoms of diabetes, bone pain and constipation (hypercalcaemia), medicines.
• Examination: blood pressure (sitting and standing), BMI and neck circumference, oedema, jugular venous pressure, chest, abdomen, prostate in men, pelvic organs in women, cognitive screen.
• Red flags: severe polydipsia, weight loss, haematuria, recurrent infection, bone pain, retention, rapid onset oedema, breathlessness, hypertension with renal impairment, saddle numbness.

• Frequency volume chart (3 days): night time volume (from going to bed to and including the first morning void), 24 hour volume, nocturnal polyuria index (night volume divided by 24 hour volume), number of night voids, maximum voided volume.
• Bloods: glucose or HbA1c, urea, creatinine and eGFR, electrolytes (sodium, potassium), calcium, albumin, B-type natriuretic peptide, thyroid function, full blood count; PSA in men after counselling.
• Urinalysis for glucose, protein, blood and specific gravity; early morning urine osmolality; urine albumin creatinine ratio.
• Echocardiography for suspected heart failure; sleep study for suspected sleep apnoea (STOP-BANG score 3 or more or Epworth above 10); renal and bladder ultrasound with residual.
• Water deprivation test if diabetes insipidus is suspected (24 hour output above 3 L with dilute urine).

• Treat the cause: optimise heart failure therapy, glycaemic control, hypercalcaemia, continuous positive airway pressure for sleep apnoea, nephrotic syndrome management, change or stop contributory drugs (amlodipine, late diuretic dose).
• Lifestyle: restrict fluids in the 2 to 4 hours before bed (avoid excessive total restriction; keep 1.5 to 2 litres per day); avoid evening caffeine and alcohol; reduce salt to below 6 g per day; leg elevation for 1 hour in the late afternoon or compression stockings during the day; take diuretics in the morning; exercise earlier in the day.
• Furosemide 20 to 40 mg orally about 6 hours before bedtime (late afternoon) to bring forward the diuresis, particularly with peripheral oedema or heart failure; monitor potassium, sodium, renal function and blood pressure.
• Desmopressin for persistent nocturnal polyuria (specialist or careful primary care use):
  • Desmopressin oral lyophilisate (melt) 25 micrograms for women or 50 micrograms for men, placed under the tongue one hour before bedtime, without water.
  • Contraindications: hyponatraemia or history of it, heart failure, uncontrolled hypertension, eGFR under 50 mL/min, SIADH, polydipsia, concurrent loop or thiazide diuretics or glucocorticoids.
  • Check serum sodium at baseline, on day 3 and at 1 month after starting and after each dose change; stop if sodium below 130 mmol/L (and reduce dose at 130 to 135 mmol/L with symptoms). Warn about headache, nausea, confusion and weight gain. Limit fluids from 1 hour before to 8 hours after. In patients over 65 sodium monitoring is key.
• Treat concurrent bladder causes: tamsulosin 400 micrograms at night for outlet obstruction; solifenacin 5 mg or mirabegron 50 mg daily for overactive bladder.
• Sleep: sleep hygiene and cognitive behavioural therapy for insomnia; avoid benzodiazepines.
• Review at 2 to 4 weeks with a repeat chart; refer to cardiology, nephrology, sleep medicine or endocrinology as indicated.