Urine Sodium, Potassium and Chloride

Urine sodium, potassium and chloride measure the kidney's handling of electrolytes. They are measured by indirect or direct ion selective electrode on a random spot sample or a timed 24-hour collection. Excretion reflects intake, extracellular volume, hormones (aldosterone, antidiuretic hormone, natriuretic peptides), tubular function and diuretic therapy. A spot sample is interpreted against a paired blood result, creatinine and urea.

The tests help to find the cause of hyponatraemia, hypernatraemia, hypokalaemia, hyperkalaemia and metabolic acidosis or alkalosis. They distinguish renal from non-renal loss, prerenal azotaemia from acute tubular necrosis, and syndrome of inappropriate antidiuresis from volume depletion. The urine anion gap and the fractional excretions use these results.

Hyponatraemia and hypokalaemia are the two commonest electrolyte disorders in hospital, each found in 15 to 30% of patients at some point. Acute kidney injury affects about 10 to 20% of hospital admissions.

Indications. Hyponatraemia, hypernatraemia, hypokalaemia, hyperkalaemia, acute kidney injury, metabolic acidosis (especially hyperchloraemic), metabolic alkalosis, polyuria, suspected mineralocorticoid excess, salt wasting, hypertension with hypokalaemia, suspected tubulopathy (Bartter and Gitelman syndromes), and assessment of dietary sodium intake.

Specimen. A random spot urine, taken at the same time as a blood sample for sodium, potassium, chloride, creatinine and urea. A 24-hour collection (complete, confirmed by creatinine excretion) is used for dietary intake and for chronic disorders. Record diuretic use and fluid intake.

Ranges depend on diet and fluid state. Local ranges take precedence.

Urine sodium. 24-hour excretion: 40 to 220 mmol/day on a normal diet (100 mmol/day corresponds to about 6 g of salt). Spot samples: under 20 mmol/L suggests sodium avidity with volume depletion, heart failure, cirrhosis or nephrotic syndrome. Over 30 to 40 mmol/L suggests renal sodium loss, syndrome of inappropriate antidiuresis, adrenal insufficiency, salt wasting nephropathy, cerebral salt wasting or diuretic effect.

Urine potassium. 24-hour excretion: 25 to 125 mmol/day, diet dependent. In hypokalaemia, urinary potassium under 20 mmol/day (or spot under 15 mmol/L, or potassium to creatinine ratio under 1.5 mmol/mmol) indicates extrarenal loss, and higher values indicate renal loss. In hyperkalaemia, a urine potassium under 40 mmol/L, a transtubular potassium gradient under 5 to 7, or a failing response to a mineralocorticoid suggests aldosterone deficiency or resistance.

Urine chloride. 24-hour excretion: 110 to 250 mmol/day. In metabolic alkalosis, a urine chloride under 20 mmol/L indicates a chloride responsive state (vomiting, nasogastric loss, remote diuretic use, post-hypercapnia, cystic fibrosis), and over 20 mmol/L indicates mineralocorticoid excess, Bartter or Gitelman syndrome, severe hypokalaemia or current diuretic use.

Urine anion gap. Urine sodium plus urine potassium minus urine chloride. A negative gap in a hyperchloraemic metabolic acidosis indicates adequate renal ammonium excretion (extrarenal bicarbonate loss, such as diarrhoea), and a positive gap indicates impaired ammonium excretion (distal renal tubular acidosis, kidney failure, hypoaldosteronism). It is unreliable with non-chloride anions in urine (ketones, hippurate).

Fractional excretion of sodium (FENa). Urine sodium times plasma creatinine divided by plasma sodium times urine creatinine, multiplied by 100. Under 1% suggests prerenal azotaemia, over 2% suggests acute tubular necrosis, and 1 to 2% is indeterminate. In patients taking diuretics, FENa is unreliable, and fractional excretion of urea (under 35% suggests prerenal) is used.

Hyponatraemia.

• Hypovolaemic, urine sodium under 20 mmol/L: extrarenal loss (vomiting, diarrhoea, burns, third spacing).
• Hypovolaemic, urine sodium over 20 mmol/L: renal loss (diuretics, adrenal insufficiency, salt losing nephropathy, cerebral salt wasting).
• Euvolaemic with urine osmolality over 100 mOsm/kg and urine sodium over 30 mmol/L: syndrome of inappropriate antidiuresis, after exclusion of adrenal, thyroid and diuretic causes.
• Hypervolaemic with urine sodium under 20 mmol/L: heart failure, cirrhosis, nephrotic syndrome. With urine sodium over 20 mmol/L: kidney failure.
• Low solute intake (beer drinkers, tea and toast): urine osmolality under 100 mOsm/kg.

Hypokalaemia.

• Low urinary potassium: poor intake, gastrointestinal loss, transcellular shift (insulin, beta agonists, alkalosis, periodic paralysis).
• High urinary potassium with hypertension: primary aldosteronism, Cushing syndrome, renal artery stenosis, Liddle syndrome, liquorice.
• High urinary potassium without hypertension: diuretics, vomiting (via bicarbonaturia and aldosterone), Bartter syndrome, Gitelman syndrome, renal tubular acidosis, hypomagnesaemia, and amphotericin.
• Gitelman syndrome shows low urinary calcium, and Bartter syndrome normal or high calcium.

Hyperkalaemia. Urine potassium low for the level and a transtubular potassium gradient under 5 indicate hypoaldosteronism or aldosterone resistance (adrenal insufficiency, type 4 renal tubular acidosis, potassium sparing drugs, trimethoprim, ACE inhibitors, calcineurin inhibitors).

Hypernatraemia. A urine osmolality under 300 mOsm/kg with polyuria points to diabetes insipidus. A concentrated urine with low sodium points to extrarenal water loss. High urine sodium with high serum sodium suggests salt loading (hypertonic saline, sodium bicarbonate) or mineralocorticoid excess.

Metabolic acidosis. A negative urine anion gap indicates diarrhoea or other gastrointestinal bicarbonate loss. A positive gap with urine pH over 5.5 indicates distal renal tubular acidosis.

Acute kidney injury. FENa under 1% with concentrated urine suggests prerenal azotaemia. FENa over 2% with muddy brown casts suggests acute tubular necrosis. Urine sodium also falls early in hepatorenal syndrome (under 10 mmol/L).

Critical values and findings needing immediate action.

• Hyponatraemia under 125 mmol/L with urine sodium and osmolality suggesting syndrome of inappropriate antidiuresis, in a patient with seizures or reduced consciousness.
• Hypokalaemia under 2.5 mmol/L with high urinary potassium, arrhythmia or paralysis.
• Hyperkalaemia over 6.5 mmol/L with a low urinary potassium or ECG changes.
• Urine sodium over 20 mmol/L with polyuria and a rising serum sodium, indicating salt wasting.
• Hypotension with a urine sodium under 10 mmol/L and rising creatinine.

Interferences and pitfalls.

• Diuretics raise urine sodium for hours to days and make fractional excretion misleading. Fractional excretion of urea is more reliable.
• Spot urine concentration varies with fluid state, so ratios to creatinine are used.
• Glycosuria, ketonuria and mannitol cause osmotic diuresis with high urine sodium despite volume depletion.
• Bicarbonaturia in metabolic alkalosis carries sodium and potassium, so urine sodium is high despite volume depletion, and urine chloride is used instead.
• In chronic kidney disease, the ability to conserve sodium is reduced.
• Indirect ion selective electrode methods can give falsely low sodium results in severe hyperlipidaemia or hyperproteinaemia (pseudohyponatraemia).
• An incomplete 24-hour collection misrepresents intake.

Special groups.

• Neonates: preterm infants have a high fractional excretion of sodium, up to 2 to 3%.
• Children: salt wasting is a feature of congenital adrenal hyperplasia and cystic fibrosis, and tubulopathies present early.
• Pregnancy: sodium retention is normal, and urine sodium is high with a high intake.
• Older adults: diuretic use and reduced renal concentration alter the interpretation, and hyponatraemia is common.
• Regions: diarrhoeal disease, salt restricted diets and heat stress alter urinary electrolytes.

Follow up tests. Serum and urine osmolality, urea, creatinine, glucose, calcium, magnesium, bicarbonate, blood gas, renin and aldosterone, morning cortisol, thyroid function tests, urine pH and anion gap, urinary calcium, urine microscopy, fractional excretion of urea, ultrasound of the kidneys, and genetic testing for tubulopathies.