Polyuria

Polyuria is urine output exceeding 3 L in 24 hours in an adult (above 40 mL/kg daily). It must be distinguished from frequency of small volumes and from nocturia. It results from two basic processes: water diuresis, where urine is dilute and solute excretion is normal, and solute diuresis, where excretion of osmoles is increased.

• Water diuresis: urine osmolality below 250 mOsm/kg, daily solute excretion below 900 mOsm. Causes are primary polydipsia, central diabetes insipidus and nephrogenic diabetes insipidus.
• Solute diuresis: urine osmolality above 300 mOsm/kg and solute excretion above 900 mOsm daily. Causes are hyperglycaemia, urea (post-obstructive, high protein feeding, recovering acute tubular injury), sodium load (saline infusion), mannitol and radiological contrast.
• Mixed: partial diabetes insipidus with solute load.

Nephrogenic diabetes insipidus is caused by lithium, hypercalcaemia, hypokalaemia, demeclocycline, amphotericin, tubulointerstitial disease, sickle cell disease and X-linked vasopressin V2 receptor mutations.

• Large volumes of pale urine, nocturia, thirst, polydipsia; craving for cold water points to diabetes insipidus
• Dehydration, hypernatraemia (sodium above 145 mmol/L), confusion in those with impaired thirst or access to water
• Hyperglycaemic symptoms in osmotic diuresis from diabetes
• History of head injury, pituitary surgery or sellar mass (central); lithium or hypercalcaemia (nephrogenic); psychiatric illness (primary polydipsia)

Red flags: serum sodium above 155 mmol/L, serum osmolality above 320 mOsm/kg, altered consciousness, visual field defect or headache suggesting pituitary mass, hyperglycaemia with ketones, urine output above 6 L daily with hypovolaemic shock.

Confirm polyuria with a 24-hour urine volume. Then:

• Glucose, urea, creatinine, sodium, potassium, calcium, osmolality (serum and urine)
• Urine osmolality: below 250 mOsm/kg indicates water diuresis; 300 to 800 suggests solute diuresis or partial defect
• Water deprivation test if sodium is normal: fluid restriction for up to 8 hours or until 3% to 5% body weight loss; hourly urine volume and osmolality, 2-hourly plasma sodium and osmolality. Stop if sodium is above 150 mmol/L or serum osmolality above 300 mOsm/kg. If urine osmolality remains below 300 mOsm/kg, give desmopressin 2 microg intramuscularly and measure osmolality at 2 and 4 hours. Central diabetes insipidus: urine osmolality rises by more than 50%. Nephrogenic: rises by less than 10%. Primary polydipsia: urine concentrates above 600 mOsm/kg during dehydration, with only small rise after desmopressin.
• Copeptin (unstimulated above 21.4 pmol/L indicates nephrogenic diabetes insipidus; after hypertonic saline stimulation, above 4.9 pmol/L indicates primary polydipsia and below 4.9 pmol/L indicates central diabetes insipidus) is an alternative where available.
• MRI pituitary for central diabetes insipidus: loss of posterior pituitary bright spot and stalk thickening.

Differentials: diabetes mellitus, hypercalcaemia, hypokalaemia, post-obstructive diuresis, diuretic use, chronic kidney disease with impaired concentrating ability.

Treat the cause

• Hyperglycaemia: insulin, fluids.
• Stop lithium, demeclocycline or other offending drugs.
• Correct hypercalcaemia and hypokalaemia.
• Primary polydipsia: behavioural treatment; avoid desmopressin because of hyponatraemia risk.

Hypernatraemia from water deficit

• Estimate deficit: 0.6 x weight (kg) x (current sodium/140 minus 1) for men; use 0.5 for women and older adults.
• Replace with oral water or 5% glucose intravenously over 48 to 72 hours.
• Lower sodium by no more than 10 mmol/L in 24 hours (0.5 mmol/L/h), checking sodium every 4 to 6 hours. If shocked, resuscitate first with balanced crystalloid.

Central diabetes insipidus

• Acute: desmopressin 1 to 2 microg intravenously or subcutaneously every 12 hours.
• Maintenance: desmopressin tablets 100 to 200 microg at night, increasing to 100 to 400 microg three times daily (total up to 1200 microg daily), or nasal spray 10 to 40 microg daily in one to three doses.
• Monitor sodium at 1 week and after each dose change, allowing a drink-to-thirst pattern and permitting once weekly breakthrough diuresis to reduce water retention.

Nephrogenic diabetes insipidus

• Sodium restriction below 2 g daily and protein restriction.
• Hydrochlorothiazide 25 to 50 mg daily; add amiloride 5 to 10 mg daily (preferred in lithium induced disease).
• Indomethacin 25 mg two to three times daily if inadequate response, with monitoring of renal function.

Special groups

• Pregnancy: transient gestational diabetes insipidus from placental vasopressinase responds to desmopressin, which is not degraded by vasopressinase.
• Older adults: lower desmopressin doses (starting 50 to 100 microg) and sodium monitoring at 3 days, owing to high hyponatraemia risk.

Refer to endocrinology for central diabetes insipidus and sellar lesions, to nephrology for tubular disease.