What is the treatment for calcium oxalate nephrolithiasis?

Treatment of Calcium Oxalate Nephrolithiasis

All patients with calcium oxalate stones should first increase fluid intake to achieve at least 2 liters of urine output daily, and if this fails to prevent recurrence, initiate pharmacologic monotherapy with thiazide diuretics, potassium citrate, or allopurinol based on metabolic profile. 1

Initial Non-Pharmacologic Management

Fluid Intake (First-Line for All Patients)

• Increase water intake to produce at least 2 liters of urine output per 24 hours 1, 2
• This intervention reduces stone recurrence by approximately 55% (relative risk 0.45,95% CI 0.24-0.84) 2
• Low baseline urine volume is a proven risk factor: male stone formers average 1,057 ml/24 hours versus 1,401 ml/24 hours in controls 3
• Recurrence rates drop significantly with high fluid intake: 12% versus 27% over 5 years in untreated patients 3

Dietary Modifications

• Maintain normal dietary calcium intake of 1,000-1,200 mg per day—do NOT restrict calcium 2
• Calcium restriction paradoxically increases urinary oxalate and stone risk 2, 4
• Limit sodium intake to 2,300 mg daily to reduce urinary calcium excretion 2
• Reduce non-dairy animal protein to 5-7 servings of meat, fish, or poultry per week 2
• Animal protein generates sulfuric acid, increasing urinary calcium and reducing citrate 2
• Limit high-oxalate foods (nuts, chocolate, tea, spinach, wheat bran) particularly in patients with hyperoxaluria 2
• Avoid sugar-sweetened beverages, especially colas acidified with phosphoric acid (relative risk 0.83 for recurrence) 2, 5
• Coffee, tea, wine, and orange juice may reduce stone risk 2

Pharmacologic Management (When Fluid Intake Fails)

The American College of Physicians recommends pharmacologic monotherapy when increased fluid intake alone fails to prevent stone formation 1. Choose ONE agent based on metabolic abnormalities:

Thiazide Diuretics (For Hypercalciuria)

• Indicated for patients with high or relatively high urinary calcium 2
• Reduces composite stone recurrence from 48.5% to 24.9% 1
• Relative risk of recurrence: 0.52 (95% CI 0.39-0.69) 5
• Effective doses studied: hydrochlorothiazide 50 mg, chlorthalidone 25-50 mg, or indapamide 2.5 mg daily 1
• Lower doses may have fewer adverse effects but efficacy for stone prevention is unknown 1

Potassium Citrate (For Hypocitraturia)

• Indicated for patients with low or relatively low urinary citrate (target >320 mg/day) 2, 6
• Reduces composite stone recurrence from 52.3% to 11.1% 1
• Relative risk of recurrence: 0.25 (95% CI 0.14-0.44) 5
• Dosing for severe hypocitraturia (<150 mg/day): Start 60 mEq/day (30 mEq twice daily or 20 mEq three times daily with meals) 6
• Dosing for mild-moderate hypocitraturia (>150 mg/day): Start 30 mEq/day (15 mEq twice daily or 10 mEq three times daily with meals) 6
• Target urinary pH of 6.0-7.0 6
• Maximum dose 100 mEq/day (higher doses not studied) 6
• Critical pitfall: Do NOT use sodium citrate or sodium bicarbonate—the sodium load increases urinary calcium excretion 7

Allopurinol (For Hyperuricosuria)

• Indicated for patients with recurrent calcium oxalate stones who have hyperuricosuria and normal urinary calcium 2
• Reduces composite stone recurrence from 55.4% to 33.3% 1
• Relative risk of recurrence: 0.59 (95% CI 0.42-0.84) 5
• Dosing: 200-300 mg daily in divided doses or as single dose 8
• Adjust based on 24-hour urinary urate determinations 8
• Maintain fluid intake sufficient to yield at least 2 liters daily urinary output 8

Combination Therapy

• Combination therapy (thiazide plus citrate or thiazide plus allopurinol) is NOT more effective than monotherapy 1
• Stick with single-agent therapy unless monotherapy clearly fails 1

Monitoring and Follow-Up

Metabolic Evaluation

• Obtain 24-hour urine collection to assess volume, pH, calcium, oxalate, uric acid, citrate, sodium, potassium, and creatinine 2
• Perform baseline collection while patient follows usual diet 9
• Repeat at 6 months after initiating therapy to assess response 7
• Continue annual 24-hour urine collections to monitor adherence 7

Laboratory Monitoring on Pharmacotherapy

• Monitor serum electrolytes (sodium, potassium, chloride, CO2), creatinine, and complete blood count every 4 months 6
• More frequent monitoring in patients with cardiac disease, renal disease, or acidosis 6
• Perform periodic electrocardiograms 6
• Discontinue treatment if: hyperkalemia develops, significant rise in creatinine, or significant fall in hematocrit/hemoglobin 6

Critical Pitfalls to Avoid

• Never restrict dietary calcium—this increases urinary oxalate and stone risk 2, 4
• Avoid calcium supplements unless specifically indicated; prefer dietary calcium sources consumed with meals to bind oxalate 2
• Do not use sodium-based alkali (sodium citrate/bicarbonate) instead of potassium citrate 7
• Do not use combination therapy as first-line—monotherapy is equally effective with fewer side effects 1
• Do not ignore vitamin C supplements—vitamin C metabolizes to oxalate and increases stone risk at doses >1000 mg/day 2

Treatment Algorithm Summary

1. All patients: Increase fluid intake to ≥2L urine output daily + dietary modifications (normal calcium, low sodium, moderate protein) 1, 2
2. If stones recur despite adequate fluid intake: Obtain 24-hour urine collection 2
3. Select monotherapy based on metabolic profile:
   • Hypercalciuria → Thiazide diuretic 2
   • Hypocitraturia → Potassium citrate 2
   • Hyperuricosuria with normal calcium → Allopurinol 2
4. Monitor response with repeat 24-hour urine at 6 months and adjust dose accordingly 7, 6

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