Calcium Phosphate Nephrolithiasis

Calcium phosphate nephrolithiasis is stone formation from hydroxyapatite or brushite (calcium hydrogen phosphate), favoured by alkaline urine (pH above 6.5 to 7) and hypercalciuria.

• It accounts for 5 to 10 percent of stones, more in women, and mixed with calcium oxalate in many.
• Causes: distal renal tubular acidosis (complete or incomplete), primary hyperparathyroidism, medullary sponge kidney, carbonic anhydrase inhibitors (acetazolamide, topiramate, zonisamide), urea-splitting infection (struvite combined), alkali overuse, high dose calcium and vitamin D, sarcoidosis, hypercalciuria, Bartter syndrome, Dent disease.
• Brushite stones are hard, resistant to shock wave lithotripsy and recur quickly.

Renal colic, haematuria, recurrent stones, flank pain, urinary infection; the stone burden is often large and bilateral.

• Distal renal tubular acidosis: hypokalaemia with muscle weakness, growth retardation in children, osteomalacia or rickets, sensorineural deafness, nephrocalcinosis.
• Primary hyperparathyroidism: bone pain, polyuria, constipation, depression, peptic ulcer, pancreatitis.
• Differential diagnosis: calcium oxalate, struvite, uric acid and cystine stones, medullary sponge kidney, nephrocalcinosis, papillary necrosis.
• Complications: obstruction, infection, progressive chronic kidney disease, bone disease, recurrence after lithotripsy.

Stone analysis (apatite or brushite); urine pH (persistently above 6.5 in the morning), 24-hour urine (calcium, citrate, volume, phosphate).

• Serum bicarbonate (low in renal tubular acidosis), potassium (low), chloride (high), creatinine, calcium, phosphate, parathyroid hormone, vitamin D; urinary anion gap.
• Ammonium chloride loading test (0.1 g/kg orally) to confirm incomplete distal renal tubular acidosis: failure to acidify to urine pH below 5.3.
• CT or ultrasound for nephrocalcinosis; intravenous urography or CT urography for medullary sponge kidney; bone density.

Supportive: fluids 3 L daily (urine output above 2.5 L); sodium below 2 g daily; adequate dietary calcium 1000 mg daily; avoid excess alkali and calcium plus vitamin D supplements; stop acetazolamide and topiramate if possible.

Pharmacological

• Distal renal tubular acidosis: alkali replacement with potassium citrate 1 to 2 mmol/kg/day in 3 to 4 divided doses (60 to 120 mmol daily), or sodium bicarbonate 1 to 2 mmol/kg/day, aiming for serum bicarbonate of 22 mmol/L or above and normal potassium; correct hypokalaemia; this reduces calcium excretion and raises citrate.
• Idiopathic hypercalciuria with alkaline urine: thiazide (hydrochlorothiazide 25 mg twice daily) with potassium supplement; avoid potassium citrate if urine pH is persistently above 6.5 in non-acidotic patients because it may promote brushite formation.
• Urease-splitting infection: treat with antibiotics (culture directed) and acetohydroxamic acid 250 mg three times daily for struvite combination stones.
• Primary hyperparathyroidism: parathyroidectomy.
• Urinary acidification with L-methionine 500 mg three times daily is not advised.

Procedures

• Ureteroscopy with laser lithotripsy or percutaneous nephrolithotomy for brushite and apatite stones (shock wave lithotripsy often fails and can injure the kidney); remove all fragments.
• Parathyroidectomy; correction of obstruction.

Special groups: children with renal tubular acidosis (growth monitoring, alkali therapy), pregnancy (hydration), patients taking topiramate for epilepsy or migraine (alternative drug).

Red flags: nephrocalcinosis, rising creatinine, hypokalaemia with paralysis, bilateral staghorn stones, rapid recurrence.

Follow-up: repeat 24-hour urine, bicarbonate, potassium and creatinine at 8 to 12 weeks then every 6 to 12 months; imaging yearly; bone density in renal tubular acidosis.