What medications are recommended for a patient with kidney stones, including those with calcium oxalate or uric acid stones, to manage pain and prevent future stone formation?

Medications for Kidney Stones

For calcium oxalate stones, offer thiazide diuretics for hypercalciuria and potassium citrate for hypocitraturia; for uric acid stones, potassium citrate is first-line to alkalinize urine to pH 6.0-6.8, NOT allopurinol. 1

Pain Management for Acute Renal Colic

• NSAIDs are the first-line medication for acute kidney stone pain, superior to opioids for renal colic 2
• Medical expulsive therapy (MET) with alpha-blockers is recommended for uncomplicated distal ureteral stones ≤10 mm to facilitate stone passage 3

Medications for Calcium Oxalate Stones

Thiazide Diuretics (For Hypercalciuria)

• Offer thiazide diuretics to patients with high or relatively high urinary calcium (>200 mg/24hr) and recurrent calcium stones 1, 4
• Effective dosing regimens include:
  • Hydrochlorothiazide 25 mg twice daily OR 50 mg once daily 1
  • Chlorthalidone 25 mg once daily 1
  • Indapamide 2.5 mg once daily 1
• Thiazides reduce stone recurrence by 52% (relative risk 0.52,95% CI 0.39-0.69) 5
• Must combine with sodium restriction (<2,300 mg/day) to maximize hypocalciuric effect and limit potassium wasting 1, 4
• Potassium supplementation (citrate or chloride) is often needed to prevent hypokalemia 1

Potassium Citrate (For Hypocitraturia)

• Offer potassium citrate to patients with low or relatively low urinary citrate (<320 mg/day) 1, 6
• Reduces stone recurrence by 75% (relative risk 0.25,95% CI 0.14-0.44) 5
• For severe hypocitraturia (<150 mg/day): Start 60 mEq/day divided as 30 mEq twice daily or 20 mEq three times daily with meals 6
• For mild-moderate hypocitraturia (>150 mg/day): Start 30 mEq/day divided as 15 mEq twice daily or 10 mEq three times daily with meals 6
• Target urinary citrate >320 mg/day, ideally approaching 640 mg/day 6
• Never use sodium citrate instead—the sodium load increases urinary calcium excretion and worsens stone risk 1, 4
• Doses >100 mEq/day have not been studied and should be avoided 6

Allopurinol (For Hyperuricosuria with Normocalciuria)

• Offer allopurinol ONLY to patients with recurrent calcium oxalate stones who have hyperuricosuria (>800 mg/day in men, >750 mg/day in women) AND normal urinary calcium 1, 7
• Reduces stone recurrence by 41% (relative risk 0.59,95% CI 0.42-0.84) in this specific population 5
• Typical dosing: 200-300 mg/day 8
• Hyperuricemia is NOT required for allopurinol therapy—only hyperuricosuria with normocalciuria 1
• Effectiveness in patients with hypercalciuria has not been established 1

Combination Therapy

• Offer thiazide diuretics and/or potassium citrate to patients with recurrent calcium stones when other metabolic abnormalities are absent or have been addressed but stone formation persists 1

Medications for Uric Acid Stones

Potassium Citrate (First-Line)

• Potassium citrate is first-line therapy for uric acid stones to alkalinize urine to pH 6.0-6.8 1, 6
• Most uric acid stone formers have low urinary pH (<5.5) rather than hyperuricosuria as the primary problem 1, 8
• Urine alkalinization with potassium citrate can dissolve existing uric acid stones 8
• Dosing follows same protocol as for calcium stones (see above) 6

Allopurinol (NOT First-Line)

• Do NOT routinely offer allopurinol as first-line therapy for uric acid stones 1
• Allopurinol is reserved for hyperuricosuric patients with recurrent uric acid stones and/or gout who fail alkalinization therapy 8
• Reducing uric acid excretion will not prevent stones if urine remains acidic 1

Medications for Calcium Phosphate Stones

• Thiazide diuretics for high urinary calcium 9
• Potassium citrate for low urinary citrate 9
• Consider combination therapy if stone formation persists despite addressing individual abnormalities 9

Medications for Cystine Stones

• Potassium citrate to raise urinary pH to 7.0 1
• Cystine-binding thiol drugs (tiopronin preferred over d-penicillamine) for patients unresponsive to dietary modifications and alkalinization or with large recurrent stone burdens 1

Essential Dietary Adjuncts to Medication

• Increase fluid intake to achieve ≥2-2.5 liters urine output daily—this is the single most important intervention 4, 5
• Maintain normal dietary calcium 1,000-1,200 mg/day from food sources—never restrict calcium 4, 5
• Limit sodium to 2,300 mg/day to enhance thiazide effectiveness and reduce urinary calcium 1, 4
• Reduce non-dairy animal protein to 5-7 servings/week 4, 5

Monitoring Requirements

• Obtain 24-hour urine collection within 6 months of starting therapy to assess response 1
• Measure: volume, pH, calcium, oxalate, uric acid, citrate, sodium, potassium, creatinine 1, 9
• After initial follow-up, obtain annual 24-hour urine collections or more frequently if stones remain active 1
• Periodic blood testing (electrolytes, creatinine, CBC) every 4 months for patients on pharmacologic therapy, more frequently with cardiac/renal disease 6
• Perform ECGs periodically in patients on potassium citrate 6

Critical Pitfalls to Avoid

• Never restrict dietary calcium—this paradoxically increases stone risk by increasing urinary oxalate absorption 4, 5
• Never use sodium citrate instead of potassium citrate—sodium increases urinary calcium excretion 1, 4
• Never use allopurinol as first-line for uric acid stones—alkalinization with potassium citrate is primary therapy 1
• Never prescribe allopurinol for calcium oxalate stones without documented hyperuricosuria AND normocalciuria 1, 7
• Discontinue potassium citrate if hyperkalemia, significant creatinine rise, or significant drop in hemoglobin/hematocrit occurs 6
• Potassium citrate is contraindicated in patients with hyperkalemia or conditions predisposing to hyperkalemia 6