Management of Mixed Uric Acid (20%) and Calcium Oxalate (80%) Stones
Potassium citrate is the single best first-line therapy for mixed uric acid and calcium oxalate stones because it simultaneously addresses both stone components by alkalinizing urine to dissolve uric acid and increasing urinary citrate to inhibit calcium oxalate crystallization. 1, 2
Primary Pharmacologic Therapy
Start potassium citrate as first-line treatment targeting a urinary pH of 6.0-6.5, which optimally dissolves uric acid while preventing calcium phosphate precipitation. 1, 3
Initial dosing: Begin with 30 mEq/day (15 mEq twice daily or 10 mEq three times daily with meals) for mild-moderate hypocitraturia, or 60 mEq/day (30 mEq twice daily or 20 mEq three times daily) for severe hypocitraturia (urinary citrate <150 mg/day). 2
Mechanism: Potassium citrate raises urinary pH to increase uric acid solubility while simultaneously increasing urinary citrate, which potently inhibits both calcium oxalate and calcium phosphate crystallization. 1, 3
Preference over sodium citrate: Potassium citrate is strongly preferred because sodium loading increases urinary calcium excretion and may paradoxically promote more calcium oxalate stone formation. 1, 4
Critical pH Target and Monitoring
Maintain urinary pH between 6.0-6.5—this is the therapeutic sweet spot. 1, 4
Avoid pH >7.0: Raising pH above 7.0 significantly increases calcium phosphate stone formation risk, converting your stone problem from one type to another. 1, 4
Monitoring schedule: Obtain 24-hour urine testing within 6 months of initiating treatment to assess urinary citrate, pH, calcium, oxalate, uric acid, and sodium, then annually or more frequently based on stone activity. 1, 3
Target urinary citrate: Aim for >320 mg/day, ideally approaching the normal mean of 640 mg/day. 2
When NOT to Use Allopurinol First-Line
Do not use allopurinol as first-line therapy unless documented hyperuricosuria (>800 mg/day in men, >750 mg/day in women) is present. 1, 4, 5
Rationale: Most uric acid stone formers have unduly acidic urine (pH <5.5) as the primary problem, not hyperuricosuria—reducing uric acid excretion will not prevent stones if urine remains acidic. 1, 4
Allopurinol indication: Reserve allopurinol (200-300 mg/day) only for patients with documented hyperuricosuria on 24-hour urine collection after potassium citrate has been initiated. 5
Essential Dietary and Fluid Modifications
Increase fluid intake to produce ≥2 liters of urine output daily—this is non-negotiable. 1, 4, 2
Dietary calcium: Maintain normal dietary calcium intake of 1,000-1,200 mg/day from food sources to bind intestinal oxalate and prevent calcium oxalate formation; paradoxically, low calcium diets increase stone risk. 1
Sodium restriction: Limit sodium to ≤2,300 mg/day because dietary sodium directly increases urinary calcium excretion, worsening the calcium oxalate component. 1, 4
Calcium supplement caveat: Avoid calcium supplements as they may increase stone risk, unlike dietary calcium from food. 1
Additional Therapy for Hypercalciuria
If 24-hour urine shows high or relatively high urinary calcium with recurrent stones, add thiazide diuretics to the potassium citrate regimen. 1
- This addresses the calcium oxalate component more aggressively in patients with persistent hypercalciuria despite dietary modifications. 1
Follow-Up Protocol
Serum monitoring: Check serum electrolytes (sodium, potassium, chloride, CO2), creatinine, and complete blood count every 4 months, more frequently in patients with cardiac or renal disease. 2
Discontinuation criteria: Stop potassium citrate if hyperkalemia develops, serum creatinine rises significantly, or hemoglobin/hematocrit falls significantly. 2
Urine monitoring: Repeat 24-hour urine collection within 6 months of treatment initiation, then annually to assess metabolic response and adjust therapy. 1, 3