Renal Salt Wasting

Renal salt wasting is inappropriate urinary loss of sodium despite a contracted extracellular volume, producing hypovolaemia, often with hyponatraemia, and a urinary sodium concentration that stays above 20 mmol/L (frequently above 40 mmol/L) when the kidney should be conserving sodium. It is a feature of many different disorders rather than a disease in itself.

Causes by site and mechanism:

• Diuretic effect: loop and thiazide diuretics, acetazolamide, osmotic agents
• Mineralocorticoid deficiency or resistance: primary adrenal insufficiency, hyporeninaemic hypoaldosteronism, pseudohypoaldosteronism, drugs (spironolactone, trimethoprim, heparin, ACE inhibitors)
• Tubular defects: Bartter syndrome, Gitelman syndrome, Fanconi syndrome, cystinosis, nephronophthisis
• Salt losing nephropathies: chronic tubulointerstitial disease, reflux nephropathy, polycystic kidney disease, obstructive uropathy, analgesic nephropathy, sickle cell nephropathy, recovery phase of acute tubular injury, post-obstructive diuresis
• Toxins: cisplatin, amphotericin B, lithium, ifosfamide
• Cerebral salt wasting: hyponatraemia with volume contraction after subarachnoid haemorrhage, traumatic brain injury, neurosurgery or intracranial infection, thought to result from raised natriuretic peptides and reduced sympathetic renal tone

Cerebral salt wasting and the syndrome of inappropriate antidiuresis both produce hyponatraemia with high urinary sodium and low serum osmolality. The distinction is extracellular volume: contracted in cerebral salt wasting, normal or mildly expanded in antidiuresis. The treatment is opposite, since fluid restriction in cerebral salt wasting worsens hypovolaemia and, after subarachnoid haemorrhage, increases the risk of cerebral infarction from vasospasm.

• Thirst, salt craving, postural dizziness, weakness, muscle cramps
• Postural hypotension (fall in systolic pressure of 20 mmHg or more), tachycardia, dry mucous membranes, reduced skin turgor, low jugular venous pressure
• Polyuria and nocturia in tubular disease
• Neurological features of hyponatraemia when sodium is below 125 mmol/L: nausea, headache, confusion, seizures
• Failure to thrive, growth retardation and vomiting in infants with tubular defects
• Hyperpigmentation, weight loss and hypoglycaemia in adrenal insufficiency
• Hypokalaemia and alkalosis in Bartter and Gitelman syndromes; hyperkalaemia and acidosis in mineralocorticoid deficiency

Red flags: sodium below 120 mmol/L or any neurological symptoms, potassium above 6.0 mmol/L with salt wasting (adrenal crisis or pseudohypoaldosteronism), systolic pressure below 90 mmHg, recent subarachnoid haemorrhage, infants with vomiting and weight loss.

• Serum sodium, potassium, chloride, bicarbonate, urea, creatinine, glucose, calcium, magnesium and osmolality
• Spot urine sodium, potassium, chloride and osmolality: urine sodium above 20 mmol/L with clinical hypovolaemia; urine chloride above 20 mmol/L distinguishes tubular loss from extrarenal loss
• Fractional excretion of sodium above 1% in volume depletion indicates renal loss (above 2% in tubular injury); use fractional excretion of urea (above 50%) if diuretics have been taken
• Serum uric acid and fractional excretion of urate (low serum urate with fractional excretion above 10% persisting after correction of hyponatraemia suggests antidiuresis; normalisation after correction fits cerebral salt wasting)
• Morning cortisol, short corticotropin stimulation test (cortisol below 450 nmol/L at 30 minutes is a failed response), renin and aldosterone
• Renal ultrasound for obstruction and structure; urinalysis for glycosuria, aminoaciduria and phosphaturia
• Genetic testing for tubular disorders
• Differentiating antidiuresis: response to isotonic saline 1 L over 4 hours; sodium rises in cerebral salt wasting and falls in antidiuresis

Differentials: antidiuresis, diuretic abuse (urine diuretic screen), vomiting (urine chloride below 20 mmol/L), gastrointestinal loss (urine sodium below 20 mmol/L), primary polydipsia.

First line: restore volume and sodium

• Isotonic saline 0.9%, 500 mL over 30 minutes to 1 hour, repeated while hypotension persists and monitoring sodium every 4 to 6 hours.
• Limit sodium correction to 8 to 10 mmol/L in 24 hours (8 mmol/L in the high risk group: alcohol misuse, malnutrition, hypokalaemia, liver disease, sodium at or below 105 mmol/L). Overcorrection risks osmotic demyelination; if exceeded, give desmopressin 2 microg intravenously every 6 to 8 hours with 5% glucose 3 mL/kg/h to re-lower sodium.
• Severe symptoms (seizure, coma): hypertonic saline 3%, 150 mL intravenously over 20 minutes, repeated once or twice until symptoms resolve or sodium rises by 5 mmol/L; then stop and limit the total rise to 8 to 10 mmol/L in 24 hours.

Cerebral salt wasting

• Fludrocortisone 0.1 to 0.2 mg orally twice daily (maximum 0.4 mg daily), with potassium monitoring.
• Oral sodium chloride 1 to 2 g three times daily, increased to 12 g daily as needed.
• Do not restrict fluids.

Mineralocorticoid deficiency

• Adrenal crisis: hydrocortisone 100 mg intravenously immediately, then 200 mg over 24 hours by infusion (or 50 mg every 6 hours), with 0.9% saline 1 L over 1 hour and continued saline for volume repletion.
• Chronic primary adrenal insufficiency: hydrocortisone 15 to 25 mg daily in two to three divided doses and fludrocortisone 0.05 to 0.2 mg daily.

Tubular and nephropathic causes

• Oral sodium chloride 3 to 6 g daily, dose titrated to urine sodium and blood pressure; sodium bicarbonate for acidosis.
• Bartter syndrome: potassium chloride 40 to 80 mmol daily, indomethacin 25 to 50 mg two to three times daily with a proton pump inhibitor, spironolactone 25 to 100 mg daily.
• Gitelman syndrome: high salt diet, potassium chloride and magnesium (magnesium glycerophosphate 4 mmol two to three times daily).
• Stop contributory drugs (diuretics, ACE inhibitors, trimethoprim, amphotericin B).

Monitoring. Daily weights, fluid balance, serum sodium and potassium every 4 to 6 hours during correction, then daily; urine sodium weekly.

Refer to endocrinology (adrenal insufficiency), neurosurgery or intensive care (subarachnoid haemorrhage), and nephrology or paediatric nephrology (tubular disorders).