What are the guidelines for managing nephrolithiasis?

Management of Nephrolithiasis

All patients with recurrent nephrolithiasis should increase fluid intake throughout the day to achieve at least 2 liters of urine output daily, and those who fail this intervention should receive pharmacologic monotherapy with a thiazide diuretic, potassium citrate, or allopurinol. 1

Acute Management of Renal Colic

NSAIDs are first-line therapy for acute renal colic pain, specifically diclofenac, ibuprofen, or metamizole, as they reduce the need for additional analgesia compared to opioids. 2 Use the lowest effective dose due to cardiovascular and gastrointestinal risks. 2

• Opioids serve as second-line agents (hydromorphine, pentazocine, or tramadol—avoid pethidine) when NSAIDs are contraindicated or provide insufficient relief. 2

• Alpha-blockers are strongly recommended for distal ureteral stones >5 mm in patients suitable for conservative management, as they facilitate stone passage. 2

• Urgent decompression is mandatory via percutaneous nephrostomy or ureteral stenting for sepsis and/or anuria in an obstructed kidney. 2 Administer antibiotics immediately and adjust based on culture results. 2

Primary Prevention: Fluid Intake

Target at least 2-2.5 liters of urine output daily by distributing fluid intake throughout the day rather than consuming large amounts at once. 1, 3 This dilutes stone-forming substances and reduces their concentration. 3

• For cystine stone formers specifically, target higher fluid intake of at least 4 liters orally per day to decrease urinary cystine concentration below 250 mg/L. 3

• Avoid grapefruit juice, which increases stone risk by 40%. 4

• Coffee, tea, beer, and wine may actually reduce stone risk, contrary to previous beliefs. 4

• Avoid soft drinks acidified with phosphoric acid (colas), though drinks acidified with citric acid (fruit-flavored sodas) do not increase risk. 1

Dietary Modifications

Maintain normal dietary calcium intake of 1,000-1,200 mg daily rather than restricting it, as adequate calcium helps reduce oxalate absorption in the gastrointestinal tract. 2, 3 Calcium restriction paradoxically increases stone risk by increasing urinary oxalate. 3

• Limit sodium intake to 2,300 mg daily or less to reduce urinary calcium excretion and enhance thiazide effectiveness. 3

• Reduce animal protein intake, particularly for patients with calcium and uric acid stones, as high protein increases purine intake and uric acid production. 3, 4

• Increase fruit and vegetable intake (excluding high-oxalate varieties) to raise urinary pH naturally and increase citrate excretion. 4

• Consume calcium from foods primarily at meals to enhance gastrointestinal binding of oxalate. 3

Pharmacologic Management

When to Initiate Pharmacotherapy

Start pharmacologic monotherapy when increased fluid intake fails to reduce stone formation in patients with active recurrent disease. 1

Calcium Stones (80% of all stones)

Choose one of three equally effective monotherapy options: 1

• Thiazide diuretics: Hydrochlorothiazide 25 mg twice daily or 50 mg once daily, chlorthalidone 25 mg daily, or indapamide 2.5 mg daily. 3, 5

• Potassium citrate: For patients with low or relatively low urinary citrate (hypocitraturia). 3, 5

  • Severe hypocitraturia (urinary citrate <150 mg/day): Start 60 mEq/day (30 mEq twice daily or 20 mEq three times daily with meals). 5
  • Mild to moderate hypocitraturia (urinary citrate >150 mg/day): Start 30 mEq/day (15 mEq twice daily or 10 mEq three times daily with meals). 5
  • Maximum dose 100 mEq/day. 5

• Allopurinol: For hyperuricosuria. 1

Combination therapy is not more beneficial than monotherapy and should be avoided to minimize adverse effects. 1, 2

Uric Acid Stones

Potassium citrate is first-line pharmacological therapy to increase urinary pH to 6.0-6.5, as uric acid solubility increases substantially in this range. 2, 4, 5 Most patients have low urinary pH rather than hyperuricosuria as the predominant risk factor. 2

• For existing uric acid stones, oral chemolysis with alkalinization using citrate or sodium bicarbonate to pH 7.0-7.2 can dissolve stones. 2

• Potassium citrate is preferred over sodium citrate or sodium bicarbonate to avoid increasing urinary calcium excretion. 3, 4

Cystine Stones

Use a stepwise approach: 2

1. Increased fluid intake (4 liters orally per day)
2. Sodium and protein restriction
3. Urinary alkalinization with potassium citrate to achieve urine pH of 7.0

Monitoring and Follow-Up

Obtain 24-hour urine collection within 6 months of treatment initiation to assess response to dietary/medical therapy. 2, 3 Measure volume, pH, calcium, oxalate, uric acid, citrate, sodium, potassium, and creatinine. 2

• Continue annual 24-hour urine collections to assess adherence and metabolic response. 2, 3

• Monitor serum electrolytes (sodium, potassium, chloride, carbon dioxide), serum creatinine, and complete blood counts every 4 months, more frequently in patients with cardiac disease, renal disease, or acidosis. 5

• Obtain periodic blood testing for adverse effects: hypokalemia and glucose intolerance (thiazides), elevated liver enzymes (allopurinol, tiopronin), anemia (acetohydroxamic acid, tiopronin), and hyperkalemia (potassium citrate). 2

• Perform stone analysis for all first-time stone formers, and obtain repeat analysis in patients not responding to treatment, as stone composition may change. 2

• Discontinue treatment if hyperkalemia develops, or if there is a significant rise in serum creatinine or significant fall in blood hematocrit or hemoglobin. 5

Common Pitfalls to Avoid

• Inadequate fluid intake remains a major risk factor regardless of other interventions. 3, 4

• Using sodium bicarbonate or sodium citrate instead of potassium citrate, as sodium load increases calcium excretion. 3, 4

• Restricting dietary calcium, which paradoxically increases stone risk by increasing urinary oxalate. 3

• Overreliance on calcium supplements rather than dietary calcium sources, as supplements should be consumed with meals to bind oxalate. 3

• Excessive vitamin C supplementation, which can increase oxalate excretion. 3

Special Populations

High-risk first-time stone formers (solitary kidney, hypertension, large stone burden, or refractory to other measures) might benefit from pharmacologic therapy even after a single stone episode. 3

Patients with malabsorptive conditions (inflammatory bowel disease, gastric bypass) may benefit from more restrictive oxalate diets and higher calcium intakes. 3