Hypocitraturia

Hypocitraturia is low urinary citrate excretion (below 1.7 mmol/day or 320 mg/day in adults; below 0.13 mmol/kg in children) that promotes calcium stone formation.

• Citrate binds urinary calcium and inhibits crystal nucleation and growth, so deficiency promotes calcium oxalate and calcium phosphate stones.
• It is present in 20 to 60 percent of stone formers, alone or with other abnormalities.
• Causes: distal renal tubular acidosis, chronic diarrhoea and malabsorption, hypokalaemia (thiazides, diuretic overuse, Bartter syndrome), metabolic acidosis, urinary tract infection, high animal protein and acid-ash diets, low fruit and vegetable intake, acetazolamide, topiramate, ACE inhibitors, strenuous exercise, starvation and ketogenic diets, and idiopathic.

Recurrent calcium stones, renal colic, haematuria, nephrocalcinosis; often no symptoms beyond stones.

• Features of the cause: muscle weakness from hypokalaemia, diarrhoea, growth failure in renal tubular acidosis.
• Differential diagnosis: hypercalciuria, hyperoxaluria, hyperuricosuria, low urine volume as independent or coexisting causes, struvite stones, cystine stones.
• Complications: recurrent stone disease, obstruction, infection, chronic kidney disease, nephrocalcinosis and bone disease from underlying acidosis.

24-hour urine citrate (two collections on usual diet), with volume, pH, calcium, oxalate, uric acid, sodium, creatinine.

• Serum bicarbonate, potassium, chloride, creatinine, calcium, parathyroid hormone.
• Urine pH persistently above 5.5 with low serum bicarbonate indicates distal renal tubular acidosis; ammonium chloride loading test (0.1 g/kg orally) for incomplete forms.
• Stool tests and malabsorption work-up when chronic diarrhoea; stone analysis; imaging for stones and nephrocalcinosis.

Supportive

• Fluids to produce urine above 2.5 L daily; increase fruit and vegetables (alkali load), reduce animal protein to 0.8 to 1 g/kg/day, sodium below 2 g daily, reduce cola and acid drinks.
• Lemon or lime juice: 120 mL of juice concentrate diluted in 2 L water daily provides about 40 to 60 mmol citrate equivalent (the effect on citrate is modest).

Pharmacological

• Potassium citrate 30 to 60 mmol daily in 2 to 3 divided doses with meals (slow release tablets 10 mmol: 2 tablets three times daily), titrated to urinary citrate above 2.5 mmol/day and urine pH 6.0 to 7.0.
• Sodium bicarbonate 1 g (12 mmol) three times daily or sodium citrate when potassium must be avoided (hyperkalaemia, advanced chronic kidney disease); sodium load may raise urinary calcium.
• Correct hypokalaemia (potassium chloride 20 to 40 mmol daily) and stop or adjust causative drugs (acetazolamide, topiramate); treat diarrhoea.
• Distal renal tubular acidosis: potassium citrate 1 to 2 mmol/kg/day in 3 to 4 doses (children 2 to 4 mmol/kg/day).
• Add thiazide (hydrochlorothiazide 25 mg twice daily) for coexisting hypercalciuria, with potassium citrate to offset hypokalaemia.

Contraindications and cautions: hyperkalaemia, advanced renal impairment (eGFR below 30), active urinary infection with urea-splitting organisms (alkalinisation promotes struvite), peptic ulcer or delayed gastric emptying (use liquid formulation), pregnancy (use under supervision).

Procedures: stone removal (lithotripsy, ureteroscopy, percutaneous nephrolithotomy) as indicated.

Red flags: persistent metabolic acidosis, hypokalaemia with paralysis, urinary infection with rising pH, rising creatinine.

Follow-up: 24-hour urine and serum potassium, bicarbonate and creatinine at 4 to 12 weeks after starting, then every 6 to 12 months; urine pH monitoring (dipstick at home); imaging yearly.