What medications are known to cause kidney stones?

Medications Known to Cause Kidney Stones

Indinavir is the most notorious medication for causing kidney stones, with crystalluria occurring in 20% of treated patients, while other high-risk drugs include sulfonamides, topiramate, and certain antibiotics like ciprofloxacin and ceftriaxone. 1

Direct Stone-Forming Medications (Crystallization in Urine)

Antiretroviral Agents

• Indinavir causes nephrolithiasis as its major side effect due to pH-dependent solubility in urine, with symptomatic stones being common 2, 1
• Risk factors for indinavir stones include low lean-body mass, doses of 1000 mg twice daily, concomitant trimethoprim-sulfamethoxazole use, and coinfection with hepatitis B or C 2, 1
• Ritonavir-boosted indinavir regimens further increase nephrolithiasis risk through higher peak drug concentrations 1
• Atazanavir and other protease inhibitors are among the most frequent causes of drug-induced calculi in HIV patients 3
• Pyuria secondary to indinavir has been associated with gradual loss of renal function unrelated to obstructive symptoms 2

Antibiotics and Antimicrobials

• Sulfonamides (particularly sulfadiazine used for cerebral toxoplasmosis) cause intratubular crystal precipitation leading to acute renal failure 2, 1, 3
• Ciprofloxacin causes intratubular crystal precipitation; avoid rapid intravenous bolus and ensure adequate hydration 2, 1
• Ceftriaxone may induce nephrolithiasis in subjects receiving high doses or long-term treatment 3

Antiviral Agents

• Acyclovir causes intratubular crystal precipitation and acute renal failure when given as rapid intravenous bolus without adequate hydration 2, 1
• Foscarnet similarly causes crystal-induced acute renal failure and requires hydration and dose adjustment for renal dysfunction 2, 1

Other Direct Stone Formers

• Ephedrine-containing preparations in subjects receiving high doses or long-term treatment 3
• Approximately 20 other molecules may induce nephrolithiasis through direct crystallization 3

Metabolically-Induced Stone Formation

Carbonic Anhydrase Inhibitors

• Topiramate causes kidney stones in 1.5% of adults during adjunctive epilepsy therapy (2-4 times greater than expected in untreated populations) and 1.3% during monotherapy 4
• Topiramate promotes stone formation by reducing urinary citrate excretion and increasing urinary pH 4
• Concomitant use of topiramate with other carbonic anhydrase inhibitors or ketogenic diet increases kidney stone risk and should be avoided 4
• Acetazolamide and dichlorphenamide similarly promote stone formation through the same mechanism 4, 3

Calcium and Vitamin D Supplements

• Uncontrolled calcium/vitamin D supplements can provoke metabolically-induced calculi 3
• Calcium supplements (as opposed to dietary calcium) may increase stone risk 1

Other Metabolic Disruptors

• Probenecid can cause hematuria, renal colic, costovertebral pain, and formation of uric acid stones in gouty patients 5
• Certain diuretics can alter renal blood flow and intrarenal hemodynamics, increasing stone risk 1, 6

Chemotherapy and Oncologic Agents

• Methotrexate causes crystalline nephropathy through intratubular crystal precipitation 2
• Pemetrexed can cause crystalline nephropathy 2

Critical Prevention Strategies

Hydration Requirements

• Daily intake of at least 1.5 liters of water prevents stone formation, particularly in high-risk patients 2, 1
• Patients on topiramate should maintain increased fluid intake to lower concentration of crystallizing substances 4
• Patients on stone-forming medications should maintain urine output of at least 2 liters daily 1

Administration Precautions

• Avoid rapid intravenous bolus administration of acyclovir, ciprofloxacin, and foscarnet 2, 1
• Adjust doses for renal dysfunction in patients receiving potentially nephrotoxic medications 2, 1

Urinary Alkalinization

• For patients on probenecid, alkalization of urine helps prevent uric acid stone formation 5
• Monitor acid-base balance when alkali is administered 5

Monitoring and Risk Assessment

Clinical Monitoring

• Monitor for crystalluria in patients taking indinavir, with urinalysis showing pyuria even without visible crystals 2, 1
• Perform periodic blood testing to assess for adverse effects of pharmacological therapy 7
• Monitor high-risk patients more closely with periodic urinalysis and imaging 1

Environmental and Patient Factors

• Environmental conditions (temperature, atmospheric pressure, humidity) affect indinavir nephrolithiasis risk 2, 1
• Coinfection with hepatitis B or C increases risk of indinavir-related stones 2, 1
• Obesity increases the risk of kidney stones 6

Common Pitfalls to Avoid

• Do not combine topiramate with other carbonic anhydrase inhibitors or ketogenic diet without considering increased stone risk 4
• Do not administer acyclovir, ciprofloxacin, or foscarnet as rapid IV bolus 2, 1
• Do not neglect hydration counseling in patients on stone-forming medications 1, 4
• Protease inhibitors, antibiotics, and some diuretics increase the risk of some types of kidney stones, and patients should be counseled about these risks 6