Targeted prevention rests on stone composition and the 24-hour urine. Dietary measures apply to all stone formers, while drug therapy is matched to the specific metabolic abnormality.
Dietary Therapy
Six measures reduce recurrence: increase fluid, limit sodium, keep calcium intake normal, limit oxalate, increase fruit and vegetables, and limit non-dairy animal protein.
- Fluid — target urine output >2.5 L/day (an RCT showed 12% vs 27% recurrence at 5 years). The absolute volume matters more than the type of fluid; citrate-rich citrus juices and citric-acid-based sodas may help, whereas phosphoric-acid colas and sugar-sweetened drinks raise risk (coffee, tea, and alcohol are associated with lower risk).
- Sodium — limit to ≤100 mEq (2,300 mg)/day; high sodium raises urinary calcium and pH and lowers citrate.
- Calcium — keep at the RDA (1,000–1,200 mg/day); a low-calcium diet leaves unbound gut oxalate, increasing oxalate absorption and urinary oxalate. Calcium citrate supplements taken with meals are preferred.
- Oxalate — limit oxalate-rich foods (spinach, beets, chocolate, nuts, tea) while maintaining normal calcium; most useful in enteric hyperoxaluria. Limit vitamin C (a substrate for oxalate).
- Fruit and vegetables — increase to raise urinary citrate (for low-citrate calcium formers).
- Animal protein — limit (it raises urinary calcium, oxalate, and uric acid); high-purine foods include anchovies, sardines, and organ meats.
- Cystine formers need a higher fluid target (≥4 L/day) plus sodium and protein restriction.
A low-carbohydrate, high-protein weight-loss diet increases both stone and bone-loss risk. Vitamin D supplementation is controversial — monitor 24-hour urinary calcium during repletion.
Pharmacologic Therapy
| Stone / abnormality | First-line drug | Key points |
|---|---|---|
| Calcium + hypercalciuria | Thiazide | Pair with dietary sodium restriction; add potassium (citrate) |
| Calcium + hypocitraturia | Potassium citrate | First-line for RTA, thiazide-induced, and idiopathic hypocitraturia |
| Calcium oxalate + hyperuricosuria (normal urinary Ca) | Allopurinol | Also limit animal protein; hyperuricaemia not required |
| Uric acid | Potassium citrate (alkalinise) | Target pH >5.5 (AUA 6.0, CUA 6.5); avoid >7.0 (calcium phosphate risk) |
| Cystine | Fluid + alkalinisation + Na/protein restriction | Target pH 7.0; add a thiol (tiopronin) if refractory |
| Struvite | Surgical clearance | AHA only after surgical options exhausted |
Calcium Stones
Thiazides stimulate distal calcium reabsorption and, via mild volume depletion, enhance proximal sodium/calcium reabsorption. Chlorthalidone (25 mg/day) and indapamide (2.5 mg/day) are preferred over hydrochlorothiazide (long-acting, once daily). Always combine with sodium restriction (a sodium load blunts the hypocalciuric effect). Adverse effects: lassitude (most common) and a metabolic cluster — three "hypers" (hyperglycaemia, hyperlipidaemia, hyperuricaemia), three "hypos" (hypokalaemia, hypomagnesaemia, hypocitraturia), and metabolic alkalosis. Give potassium (preferably potassium citrate) to offset hypokalaemia and glucose intolerance, or add amiloride/spironolactone (avoid triamterene). A thiazide challenge can unmask primary hyperparathyroidism, and thiazides lose efficacy in ~25% over the long term (calcitonin escape).
Potassium citrate corrects hypocitraturia and the acidosis/hypokalaemia of distal RTA, and is preferred over sodium citrate (a sodium load promotes hypercalciuria); raising urine pH too far risks calcium phosphate stones. For patients with no identified risk factor, potassium citrate is a reasonable first-line agent given its low side-effect profile.
Uric Acid Stones
Potassium citrate is first-line — alkalinise the urine above pH 5.5 (AUA target 6.0, CUA 6.5) to keep uric acid dissolved, without exceeding 7.0. Allopurinol (300 mg/day; xanthine oxidase inhibitor) is reserved as an adjunct when alkalinisation fails, since most uric acid formers have low urine pH rather than hyperuricosuria. Acetazolamide can further raise urine pH in patients already on citrate (up to 50% stop it for side effects).
Cystine Stones
First-line is high fluid intake (≥4 L/day), urinary alkalinisation (potassium citrate to pH 7.0), and sodium/protein restriction. Cystine-binding thiols — tiopronin (α-mercaptopropionylglycine, preferred for lower toxicity), D-penicillamine (causes pyridoxine/B6 deficiency — supplement), and captopril (ineffective) — are added for refractory disease or large stone burdens; they form a more soluble cystine–drug mixed disulfide.
Struvite Stones
Management is primarily surgical (complete stone clearance); medical therapy aims to prevent recurrence. Acetohydroxamic acid (AHA), a urease inhibitor, is offered only after surgical options are exhausted — its serious toxicity (haemolytic anaemia and deep vein thrombosis, each ~15%) limits use. Phosphate therapy is contraindicated.
Other Situations
Fish oil is a first-line option for mild–moderate hypercalciuria; primary hyperparathyroidism with stones is treated by adenoma excision; enteric hyperoxaluria is managed with fluids, calcium, and potassium citrate (60–120 mEq/day); and hypomagnesuric calcium nephrolithiasis with magnesium plus potassium citrate. In neonates, furosemide-induced nephrolithiasis is managed by stopping furosemide; childhood stones should raise suspicion of an inherited disorder (cystinuria, distal RTA, primary hyperoxaluria).
Follow-Up
Obtain a 24-hour urine within 6 months of starting therapy, then annually (or more often by activity). Monitor bloods for drug toxicity — thiazides (hypokalaemia, glucose intolerance), allopurinol/tiopronin (liver enzymes), AHA/tiopronin (anaemia), potassium citrate (hyperkalaemia) — and image periodically for stone growth.
Self-Test
1. List the dietary measures that reduce stone recurrence. Increase fluid (urine >2.5 L/day), limit sodium, keep calcium intake normal (1,000–1,200 mg/day), limit oxalate, increase fruit and vegetables, and limit non-dairy animal protein.
2. Why is a low-calcium diet counterproductive in calcium stone formers? Insufficient gut calcium leaves more oxalate unbound, increasing intestinal oxalate absorption and urinary oxalate.
3. What are the metabolic side effects of thiazides? Three "hypers" (hyperglycaemia, hyperlipidaemia, hyperuricaemia), three "hypos" (hypokalaemia, hypomagnesaemia, hypocitraturia), and metabolic alkalosis.
4. What is the first-line therapy for uric acid stones and the target urine pH? Potassium citrate to alkalinise the urine above pH 5.5 (AUA 6.0, CUA 6.5), avoiding pH >7.0.
5. When is acetohydroxamic acid used, and what is its most serious side effect? For residual or recurrent struvite stones only after surgical options are exhausted; its most serious toxicity is haemolytic anaemia (also deep vein thrombosis).