Medications for Renal Stones

Acute Pain Management

NSAIDs are the definitive first-line medication for acute renal colic, with diclofenac 75 mg intramuscular providing superior pain relief within 30 minutes compared to opioids. 1, 2

Diclofenac, ibuprofen, or metamizole are all acceptable NSAID options, with diclofenac showing the strongest evidence for rapid pain control 1, 2
NSAIDs work by directly decreasing ureteral smooth muscle tone and spasm, addressing the underlying pain mechanism rather than just masking symptoms 2
Opioids (hydromorphine, pentazocine, or tramadol—but NOT pethidine) should be reserved only when NSAIDs are contraindicated due to cardiovascular disease, gastrointestinal comorbidities, hypertension, renal insufficiency, heart failure, or peptic ulcer risk 1, 2

Common pitfall: Using opioids as first-line therapy increases dependence risk and provides inferior pain relief compared to NSAIDs 2

Medical Expulsive Therapy (MET)

Alpha-blockers, specifically tamsulosin, should be offered for conservative management of ureteral stones, particularly those >5 mm in the distal ureter. 1, 2

MET is appropriate for uncomplicated ureteral stones up to 10 mm in diameter 1
Stone-free rates with tamsulosin are 77.3% versus 54.4% for placebo 2
Maximum duration of conservative treatment is 4-6 weeks from initial presentation 1, 2

Stone Prevention: Calcium Stones

First-Line Therapy Based on Metabolic Abnormality

For calcium stones with hypercalciuria, thiazide diuretics combined with dietary sodium restriction (≤2,300 mg/day) are first-line prevention. 3, 1

Higher doses of thiazides were studied in trials: hydrochlorothiazide 50 mg, chlorthalidone 25-50 mg, or indapamide 2.5 mg 3
Thiazides lower urinary calcium excretion and must be continued with sodium restriction to maximize the hypocalciuric effect 3, 1
Lower doses of thiazides have fewer adverse effects, but their effectiveness compared to higher doses is unknown 3

For calcium stones with hypocitraturia, potassium citrate therapy is first-line prevention. 3, 1, 4

Potassium citrate is a potent inhibitor of calcium phosphate crystallization 3, 5
Potassium citrate is preferred over sodium citrate, as the sodium load in sodium citrate increases urinary calcium excretion 3, 5, 1
Target urinary citrate >320 mg/day, ideally approaching the normal mean of 640 mg/day 4

Dosing for Potassium Citrate

Severe hypocitraturia (urinary citrate <150 mg/day): Start 60 mEq/day (30 mEq twice daily or 20 mEq three times daily with meals) 4
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) 4
Doses >100 mEq/day have not been studied and should be avoided 4

Second-Line and Combination Therapy

For calcium oxalate stones with hyperuricosuria and normal urinary calcium, allopurinol should be offered. 3

A prospective randomized controlled trial demonstrated allopurinol reduced recurrent calcium oxalate stones in patients with hyperuricosuria (urinary uric acid >800 mg/day) and normocalciuria 3
Hyperuricemia is not a required criterion for allopurinol therapy 3

For recurrent calcium stones where other metabolic abnormalities are absent or have been addressed and stone formation persists, thiazide diuretics and/or potassium citrate should be offered. 3

Common pitfall: The American College of Physicians notes that while thiazide diuretics, citrates, and allopurinol all effectively reduce calcium stone recurrence, randomized controlled trials do not link specific biochemical testing to outcomes, so any of these three agents can be used as monotherapy when increased fluid intake fails 3

Stone Prevention: Uric Acid Stones

Potassium citrate is first-line therapy for uric acid stones, with a target urinary pH of approximately 6.0. 3, 1, 4

Most patients with uric acid stones have low urinary pH rather than hyperuricosuria as the predominant risk factor 3, 1
Urinary alkalinization addresses the underlying pathophysiology more effectively than reducing uric acid production 3, 1
Oral chemolysis with citrate or sodium bicarbonate (pH 7.0-7.2) can dissolve existing uric acid stones, with an 80.5% success rate 1

Allopurinol should NOT be offered as first-line therapy for uric acid stones. 3, 1, 2

Reduction of urinary uric acid excretion with allopurinol will not prevent stones in patients with unduly acidic urine 3
Allopurinol may be considered as adjunctive therapy after urinary alkalinization is achieved 6

Common pitfall: Prescribing allopurinol as first-line therapy for uric acid stones without first addressing urinary pH with potassium citrate is a fundamental error 3, 1, 2

Stone Prevention: Cystine Stones

Potassium citrate to raise urinary pH to approximately 7.0, combined with increased fluid intake (≥4 liters/day), is first-line therapy for cystine stones. 3, 1, 4

First-line therapy also includes restriction of sodium and protein intake 3, 1
Cystine solubility increases at higher urinary pH values 3

Cystine-binding thiol drugs, such as tiopronin, should be offered to patients unresponsive to dietary modifications and urinary alkalinization, or those with large recurrent stone burdens. 3, 1

Tiopronin is possibly more effective and associated with fewer adverse events than d-penicillamine and should be considered first 3

Stone Prevention: Calcium Phosphate and Brushite Stones

Potassium citrate is first-line therapy for calcium phosphate or brushite stones with hypocitraturia, but exercise caution with excessive alkalinization. 5, 1

Potassium citrate is a potent inhibitor of calcium phosphate crystallization 3, 5
Excessive alkalinization can paradoxically promote calcium phosphate stone formation, so monitor urinary pH closely 5

Thiazide diuretics should be offered to brushite stone formers with hypercalciuria. 5, 1

Thiazides lower urinary calcium excretion and may increase the safety and efficacy of citrate therapy 5

Stone Prevention: Struvite Stones

Acetohydroxamic acid (AHA), a urease inhibitor, may be considered in high-risk patients or when surgery is not feasible, though extensive side effects may limit use. 3, 1

Struvite stones occur as a consequence of urinary infection with a urease-producing organism 3
Complete surgical removal coupled with appropriate antibiotic therapy is necessary for definitive treatment 1

Universal Preventive Measures

All patients should increase fluid intake to achieve urine volume of at least 2.5 liters daily. 1, 4

For cystine stones specifically, target at least 4 liters per day to decrease urinary cystine concentration below 250 mg/L 1
Treatment with potassium citrate should be added to a regimen that limits salt intake and encourages high fluid intake (urine volume should be at least 2 liters per day) 4

Monitoring and Follow-up

Obtain a 24-hour urine specimen within 6 months of initiating treatment to assess response to therapy. 3, 5, 1, 4

Continue annual 24-hour urine collections for ongoing monitoring, with more frequent testing depending on stone activity 5, 1
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 4
Perform periodic blood testing to monitor for adverse effects: hypokalemia with thiazides and hyperkalemia with potassium citrate 1, 4
Perform electrocardiograms periodically in patients on potassium citrate 4
Discontinue treatment if there is hyperkalemia, significant rise in serum creatinine, or significant fall in blood hematocrit or hemoglobin 4

Key Medication-Specific Considerations

Allopurinol Precautions

Fluid intake should be sufficient to yield daily urinary output of at least 2 liters to avoid theoretical possibility of xanthine calculi formation 6
Patients with decreased renal function require lower doses than those with normal renal function; lower than recommended doses should be used to initiate therapy 6
In patients with severely impaired renal function, a dose of 100 mg per day or 300 mg twice a week may be sufficient 6
Patients should be cautioned to discontinue allopurinol and consult their physician immediately at the first sign of skin rash, painful urination, blood in urine, irritation of eyes, or swelling of lips or mouth 6

Potassium Citrate Precautions

Treatment should be discontinued if there is hyperkalemia, significant rise in serum creatinine, or significant fall in blood hematocrit or hemoglobin 4
Doses greater than 100 mEq/day have not been studied and should be avoided 4

Common pitfall: Not monitoring for medication side effects, particularly electrolyte abnormalities, can lead to serious complications 1

What medications are used to manage renal stones?

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