Urine Osmolality

Urine osmolality measures the number of osmotically active particles (solutes) in each kilogram of urine water, usually by freezing point depression.

It reflects the kidney's ability to concentrate and dilute urine under the control of antidiuretic hormone (ADH), the renal medullary gradient and the delivery of solute to the collecting duct.

In health, urine osmolality varies from about 50 mOsm/kg (maximally dilute) to 1200 mOsm/kg (maximally concentrated). It is interpreted alongside serum osmolality, sodium, urine sodium and the clinical state of volume.

Urine osmolality has four main uses: to separate causes of hyponatraemia (appropriate suppression of ADH versus inappropriate release), to diagnose and classify polyuria (diabetes insipidus versus primary polydipsia versus solute diuresis), to distinguish prerenal from intrinsic acute kidney injury, and to assess concentrating capacity in chronic kidney disease. Hyponatraemia is the commonest electrolyte disorder in hospital, affecting 15 to 30% of inpatients. Polyuria (over 3 L a day) has a differential that is separated mostly by this test.

Indications. Hyponatraemia or hypernatraemia. Polyuria, polydipsia or nocturia. Suspected diabetes insipidus or syndrome of inappropriate ADH secretion. Acute kidney injury. Assessment of renal concentrating ability. Water deprivation and hypertonic saline testing. Suspected osmotic diuresis from glucose, mannitol or contrast.

Specimen. Random spot urine 5 to 10 mL, preferably a fresh sample not a first morning void unless concentrating ability is being tested. Collected in a plain sterile container. Osmolality is measured within 4 hours or refrigerated, and cloudy specimens are centrifuged. Serum for a paired osmolality and sodium is drawn at the same time.

Reference values.

• Random urine: 50 to 1200 mOsm/kg, wide range with fluid intake.
• After 12 to 14 hours of fluid restriction: over 800 mOsm/kg (usually 800 to 1200).
• After a water load: under 100 mOsm/kg.
• 24-hour urine: 300 to 900 mOsm/kg.
• Serum osmolality: 275 to 295 mOsm/kg.
• Urine to serum osmolality ratio: 1 to 3 (over 1.5 after 12 hours of restriction).

Hyponatraemia (serum sodium under 135 mmol/L).

• Urine osmolality under 100 mOsm/kg: ADH appropriately suppressed, from primary polydipsia, low solute intake (tea and toast, beer potomania).
• Urine osmolality over 100 mOsm/kg: ADH active. Urine sodium under 30 mmol/L suggests hypovolaemia, heart failure, cirrhosis or nephrotic syndrome. Urine sodium over 30 mmol/L with euvolaemia suggests syndrome of inappropriate ADH secretion (needs normal thyroid and adrenal function, no diuretics) or adrenal insufficiency or hypothyroidism.
• Syndrome of inappropriate ADH secretion criteria include serum osmolality under 275 mOsm/kg, urine osmolality over 100 mOsm/kg, euvolaemia and urine sodium over 30 mmol/L.

Polyuria (over 3 L a day).

• Urine osmolality under 300 mOsm/kg: water diuresis. Causes are central diabetes insipidus, nephrogenic diabetes insipidus and primary polydipsia (separated by water deprivation, desmopressin response and copeptin).
• Urine osmolality over 300 mOsm/kg (solute diuresis, daily solute excretion over 900 mOsm): glucose, urea, mannitol, saline loading or contrast.
• Mixed pattern at 300 to 800 mOsm/kg: partial diabetes insipidus or partial concentrating defect.

Hypernatraemia. Urine osmolality over 800 mOsm/kg with an intact response means extrarenal water loss (insensible, gastrointestinal losses, sweating). Urine osmolality under 300 mOsm/kg means diabetes insipidus or osmotic diuresis.

Acute kidney injury.

• Prerenal: urine osmolality over 500 mOsm/kg, urine sodium under 20 mmol/L, fractional excretion of sodium under 1%.
• Acute tubular necrosis: urine osmolality 250 to 350 mOsm/kg (isosthenuria), urine sodium over 40 mmol/L, fractional excretion of sodium over 2%.

Osmolar gap and urinary anion gap. Urine osmolal gap (measured minus 2 times the sum of sodium and potassium plus urea plus glucose in mmol/L) estimates ammonium excretion in metabolic acidosis, with a gap over 100 mOsm/kg indicating appropriate renal acid excretion (gastrointestinal bicarbonate loss) and a low gap indicating renal tubular acidosis.

Critical values and findings needing immediate action.

• Serum sodium under 125 mmol/L with symptoms (seizure, confusion, vomiting): hypertonic saline bolus, and the urine osmolality is sent before treatment is given.
• Hypernatraemia over 160 mmol/L with urine osmolality under 300 mOsm/kg: diabetes insipidus, urgent water replacement and desmopressin, with correction rate under 10 mmol/L in 24 hours.
• Urine output over 3 L a day with low urine osmolality and rising serum sodium: risk of severe dehydration.
• Fixed urine osmolality near 300 mOsm/kg with oliguria: acute tubular necrosis.
• Overly rapid correction of chronic hyponatraemia (over 8 to 10 mmol/L in 24 hours): risk of osmotic demyelination, and a falling urine osmolality with brisk water diuresis signals overcorrection.

Interferences and pitfalls.

• Glucose, mannitol, contrast media and urea add to osmolality without ADH effect. A glycosuria of 1 g/L adds about 5.5 mOsm/kg.
• Diuretics blunt concentrating capacity and sodium interpretation, so urine sodium is unreliable on loop or thiazide diuretics (urea or fractional excretion of urea is used).
• Osmolality is not specific gravity. Dipstick specific gravity is influenced by protein, glucose and contrast, and does not replace osmolality.
• Sample storage allows bacterial growth and precipitates, altering results.
• A random value needs the context of serum osmolality, plasma sodium and fluid intake.
• Water deprivation testing must not start with hypernatraemia or hypovolaemia, and severe polyuria with a serum osmolality over 295 mOsm/kg and urine osmolality under 300 confirms diabetes insipidus without a deprivation test.
• Chronic kidney disease, hypercalcaemia, hypokalaemia, sickle cell disease, lithium and demeclocycline cause nephrogenic concentrating defects.

Special groups.

• Children and infants: concentrating capacity is limited in neonates (maximum 600 to 700 mOsm/kg).
• Older adults: concentrating ability falls with age, with maximum values near 700 mOsm/kg, and nocturnal polyuria is common.
• Pregnancy: serum osmolality falls by 10 mOsm/kg, and gestational diabetes insipidus may occur.
• Regions: heat exposure, dehydration and rehydration practices affect baseline values.

Follow up tests. Serum osmolality and sodium, urine sodium and potassium, urea and creatinine, glucose and HbA1c, calcium and potassium, thyroid and cortisol function, copeptin, water deprivation test, desmopressin challenge, pituitary MRI for central diabetes insipidus, and renal tract ultrasound.