What are the treatment options for nephrolithiasis?

Treatment Options for Nephrolithiasis

The primary treatment for nephrolithiasis should begin with increased fluid intake to achieve at least 2 liters of urine output per day, followed by pharmacologic monotherapy with thiazide diuretics, citrate, or allopurinol if fluid therapy fails to prevent stone recurrence. 1

Non-Pharmacological Management

Fluid Intake

• Increased fluid intake spread throughout the day is the first-line treatment for preventing recurrent nephrolithiasis 1, 2
• Target should be to achieve at least 2 liters of urine output per day 1
• For severe forms of nephrolithiasis (primary or enteric hyperoxaluria or cystinuria), fluid intake should be increased to achieve 3.5-4 liters of urine output 2
• Fluid intake should be balanced between day and night to avoid urinary supersaturation during nighttime 2
• No significant difference has been observed between tap water and mineral water in preventing stone recurrence 1

Dietary Modifications

• Reducing consumption of soft drinks acidified by phosphoric acid (such as colas) can help reduce stone recurrence 1
• However, soft drinks acidified by citric acid (fruit-flavored sodas) do not show the same negative effect 1
• Maintaining normal dietary calcium intake is recommended rather than restricting it 3
• Limiting dietary oxalate may be beneficial for patients with oxalate stones 3

Pharmacological Management

When increased fluid intake fails to prevent stone formation, pharmacologic therapy should be initiated 1:

Thiazide Diuretics

• Effective in reducing calcium stone recurrence 1
• Higher doses were evaluated in studies (hydrochlorothiazide 50 mg, chlorthalidone 25 or 50 mg, indapamide 2.5 mg) 1
• Lower doses may have fewer adverse effects but their effectiveness in preventing stone recurrence is not well established 1
• Mechanism: Reduces urinary calcium excretion, particularly beneficial for patients with hypercalciuria 1

Citrate Therapy

• Effectively reduces recurrence of calcium stones 1
• Mechanism: Binds to calcium and decreases urine acidity 1
• May cause gastrointestinal side effects leading to higher withdrawal rates compared to placebo (36.0% vs. 20.0%) 1

Allopurinol

• Indicated for management of patients with recurrent calcium oxalate calculi, particularly when daily uric acid excretion exceeds 800 mg/day in males and 750 mg/day in females 4
• Mechanism: Inhibits xanthine oxidase, reducing uric acid formation 4
• Reduces both serum and urinary uric acid levels within 2-3 days of administration 4
• Generally well-tolerated with no increased risk of withdrawals compared to placebo (31.0% vs. 42.0%) 1

Treatment Algorithm Based on Stone Type

Calcium Stones (80% of all kidney stones) 1

1. First-line: Increased fluid intake to achieve 2L urine output daily
2. Second-line (if fluid therapy fails):
   • For hypercalciuria: Thiazide diuretics
   • For hypocitraturia: Citrate supplementation
   • For hyperuricosuria: Allopurinol

Uric Acid Stones

1. First-line: Increased fluid intake
2. Second-line: Allopurinol (particularly effective for uric acid stones) 4, 5
3. Urinary alkalinization may also be beneficial 5

Struvite Stones (Infection Stones)

• Complete surgical eradication of stones (percutaneous nephrolithotomy or extracorporeal shock wave lithotripsy) is required 6
• Appropriate antimicrobial therapy based on culture results 6

Clinical Considerations and Pitfalls

• Monotherapy is generally as effective as combination therapy for preventing stone recurrence 1
• Higher doses of thiazides were studied in clinical trials, but lower doses may be preferred in clinical practice to minimize side effects 1
• Patients with urinary tract obstruction due to stones require prompt drainage of the collecting system to prevent infection complications 6
• Although biochemical testing (stone composition, urine chemistry, blood chemistry) is commonly used to guide treatment selection, randomized controlled trial evidence supporting this approach is lacking 1
• For patients with recurrent stones, a detailed metabolic evaluation using 24-hour urine collections and serum tests is indicated to identify underlying abnormalities 7
• Reversible metabolic abnormalities can be identified in over 90% of recurrent stone formers 7

Monitoring and Follow-up

• Regular follow-up with clinical, laboratory, and radiological evaluation is recommended to assess treatment efficacy 8
• Patients with recurrent stones tend to have higher calcium excretion compared to those without recurrences 8
• The effectiveness of treatment can be monitored by measuring relative supersaturations of calcium oxalate, brushite, and uric acid in urine 8