Uric Acid Nephrolithiasis

Uric acid stones account for 5 to 10 percent of all urinary stones (up to 40 percent in hot, arid regions and in some Mediterranean populations). They are radiolucent on plain radiographs, but visible on CT and ultrasound. They are unique among stones in that they can be dissolved by medical therapy.

The main determinant of formation is persistently acidic urine (pH below 5.5, and often 5.0 or below). In acidic urine, uric acid (pKa 5.35) remains in its poorly soluble undissociated form. Excess uric acid excretion is not the main driver. Hyperuricosuria (above 800 mg per day in men, 750 mg in women) and low urine volume contribute.

Causes:

• Idiopathic acidic urine (about 50 percent). It is seen in obesity, insulin resistance, type 2 diabetes and metabolic syndrome, which impair renal ammonium excretion.
• Gout and hyperuricaemia.
• High purine diet (organ meat, red meat, shellfish, alcohol, fructose).
• Chronic diarrhoea and ileostomy (bicarbonate loss with dehydration).
• Myeloproliferative and lymphoproliferative disorders and tumour lysis.
• Uricosuric drugs.
• Inherited disorders (Lesch-Nyhan syndrome, glycogen storage disease type I, hypoxanthine guanine phosphoribosyltransferase deficiency).
• Dehydration.

• Renal colic, haematuria, and flank pain from ureteral obstruction by a stone, typically smooth and round or pebble like.
• Passage of sand or small stones; stones may be multiple and bilateral.
• Recurrent episodes, often with gout, metabolic syndrome or diabetes.
• Symptoms of the underlying cause: tophi and gouty arthritis, chronic diarrhoea, malignancy.
• Acute kidney injury in the setting of tumour lysis, with uric acid nephropathy (crystal precipitation in tubules).
• Often asymptomatic with staghorn shaped stones in chronic acidic urine.

• Non-contrast CT: uric acid stones are of lower attenuation (about 200 to 450 Hounsfield units, compared with over 1,000 for calcium oxalate), dual energy CT can distinguish uric acid stones from calcium stones with high accuracy; plain X-ray shows no stone (radiolucent); ultrasound shows a hyperechoic stone with shadowing.
• Urinalysis: persistently acidic urine (pH 5.0 to 5.5 and below, on repeated morning samples), uric acid crystals (rhomboid or rosette shape), and haematuria.
• Blood tests: serum uric acid (may be normal in many), creatinine, calcium, glucose and HbA1c, lipid profile, bicarbonate.
• 24-hour urine: volume, pH (low), uric acid (high in about 20 to 30 percent), creatinine, citrate, calcium, oxalate; two collections.
• Stone analysis (infrared spectroscopy) confirms the composition.
• Exclude secondary causes: haematological malignancy (blood count), myeloproliferative disorders, enzyme deficiencies in young patients, and drugs.

Medical dissolution (chemolysis) is first line for uric acid stones in the absence of infection, obstruction and sepsis.

• Urinary alkalinisation with potassium citrate (preferred) 30 to 60 mEq per day in 2 to 3 divided doses (e.g., 10 to 20 mEq three times daily, 1 to 2 tablets of 10 mEq or sustained release form). Titrate to a target urine pH of 6.5 to 7.0 (a pH above 7.0 risks calcium phosphate stones).
• Alternatively, sodium bicarbonate 650 to 1,300 mg three times daily (less preferable, because of the sodium load and calciuria).
• Monitor urine pH three times a day with dipsticks, and check serum potassium and creatinine. Alkalinisation is contraindicated in hyperkalaemia and severe renal impairment.
• Dissolution takes 4 to 8 weeks, up to 6 months, and the stone size is reviewed by imaging. Success is about 80 percent for stones of small size.
• Hydration to produce urine volume above 2.5 L per day.
• Dietary modification: reduce animal protein, organ meats, and purine rich foods. Limit alcohol (especially beer), fructose and sugar sweetened beverages. Encourage weight loss and a diet rich in fruit and vegetables (alkali forming).
• Allopurinol 100 to 300 mg daily (start 100 mg and increase by 100 mg every 2 to 4 weeks, to a target serum uric acid below 6 mg/dL). Use it for hyperuricosuria, hyperuricaemia and gout, with recurrent uric acid stones despite alkalinisation.
• Febuxostat 40 to 80 mg daily when allopurinol is not tolerated (cardiovascular caution). HLA-B*5801 testing is advised before allopurinol in high risk populations.
• Allopurinol is not required for stones with normal uric acid excretion, as alkalinisation alone is effective.
• Obstructive or infected stone: decompression with ureteric stent or nephrostomy, antibiotics, and alkalinisation through the nephrostomy tube (irrigation with sodium bicarbonate 1.5 percent or sodium citrate solution).
• Surgical removal if dissolution is unsuccessful or rapid relief is required: ureteroscopy with laser lithotripsy, shock wave lithotripsy (uric acid stones are variable in hardness, some very hard), and percutaneous nephrolithotomy for large stones.
• Tumour lysis prophylaxis: hydration (3 L/m2 per day), allopurinol 300 mg daily started 24 to 48 hours before chemotherapy, or rasburicase 0.2 mg/kg intravenously once daily for 1 to 7 days for high risk patients (avoid in G6PD deficiency).
• Treat underlying conditions: weight loss, glycaemic control (metformin and pioglitazone can raise urinary pH), and gout management.
• Follow up: urine pH monitoring, repeat CT or ultrasound at 4 to 8 weeks and then yearly, and metabolic review every 6 to 12 months. Recurrence is rare with maintained alkalinisation.