Hypercalciuric Nephrolithiasis

Hypercalciuric nephrolithiasis is kidney stone formation (calcium oxalate or calcium phosphate) driven by excess urinary calcium excretion.

• Hypercalciuria is urinary calcium above 7.5 mmol (300 mg) daily in men, above 6.25 mmol (250 mg) daily in women, or above 0.1 mmol/kg (4 mg/kg) daily.
• It is present in 30 to 60 percent of calcium stone formers.
• Mechanisms: absorptive (increased intestinal calcium absorption, vitamin D sensitivity), renal leak (impaired tubular reabsorption), and resorptive (primary hyperparathyroidism, immobilisation, malignancy).
• Other causes: distal renal tubular acidosis, sarcoidosis, hyperthyroidism, Cushing syndrome, vitamin D excess, loop diuretics, glucocorticoids, high sodium and animal protein intake, medullary sponge kidney, Dent disease.

Renal colic, haematuria, recurrent stones, family history, nephrocalcinosis; many are asymptomatic.

• Reduced bone mineral density, fractures (low bone density is frequent in idiopathic hypercalciuria).
• Hypercalcaemia features in primary hyperparathyroidism: polyuria, constipation, bone pain, peptic ulcer, depression.
• Differential diagnosis: hyperoxaluric stones, hyperuricosuric stones, hypocitraturic stones, struvite and cystine stones, medullary sponge kidney, papillary necrosis.
• Complications: obstruction, infection, chronic kidney disease, osteoporosis, nephrocalcinosis, recurrent stone disease (50 percent within 10 years).

Stone analysis; serum calcium (corrected), phosphate, parathyroid hormone, vitamin D, creatinine, bicarbonate, potassium, urate.

• Two 24-hour urine collections on usual diet at least 6 weeks after a stone episode: volume, calcium, sodium, oxalate, citrate, uric acid, magnesium, pH, creatinine.
• Fast and calcium load tests are used rarely to classify absorptive type.
• Low dose CT or ultrasound; bone mineral density.
• Exclude secondary causes: hyperparathyroidism, sarcoidosis (angiotensin converting enzyme), renal tubular acidosis, hyperthyroidism, malignancy.

Supportive

• Fluids to produce urine above 2.5 L daily; sodium below 2 g daily (high sodium raises calcium excretion); normal dietary calcium 1000 to 1200 mg daily (restriction increases stone and bone risk); animal protein 0.8 to 1 g/kg/day; reduce sugar and fructose; avoid vitamin D and calcium supplements unless needed; weight-bearing exercise.

Pharmacological

• Thiazide-type diuretic: hydrochlorothiazide 25 mg twice daily (or 50 mg daily), chlorthalidone 25 to 50 mg daily, or indapamide 2.5 mg daily, with sodium restriction (the effect is lost with high sodium intake); monitor potassium, sodium, glucose, urate and calcium; add potassium citrate or amiloride 5 mg daily to prevent hypokalaemia.
• Potassium citrate 30 to 60 mmol daily in 2 to 3 doses when urinary citrate is low or thiazide causes hypokalaemia.
• Primary hyperparathyroidism: parathyroidectomy; cinacalcet 30 mg twice daily if unfit.
• Sarcoidosis: prednisolone 20 to 40 mg daily; vitamin D intoxication: stop vitamin D and calcium, hydration.
• Resorptive hypercalciuria with low bone density: alendronate 70 mg weekly.
• Distal renal tubular acidosis: alkali (potassium citrate 1 to 2 mmol/kg/day).

Procedures: definitive stone removal by shock wave lithotripsy, ureteroscopy with laser, or percutaneous nephrolithotomy; parathyroidectomy.

Special groups: children (avoid thiazides unless needed; hydration, sodium restriction), pregnancy (hydration, avoid thiazides), elderly (monitor electrolytes), gout or diabetes (thiazide care).

Red flags: hypercalcaemia, bilateral stones, nephrocalcinosis, rising creatinine, stones in childhood.

Follow-up: repeat 24-hour urine 8 to 12 weeks after treatment changes, then yearly; electrolytes at 2 to 4 weeks after starting thiazide, then every 6 to 12 months; imaging yearly for 2 years; bone density every 2 years.