What medications can cause kidney stones?

Medications That Cause Kidney Stones

Direct Stone-Forming Medications

Certain medications directly crystallize in urine or alter metabolic pathways to promote stone formation, and clinicians must routinely query patients about these drugs during kidney stone evaluation. 1

Antiretroviral Agents

• Indinavir is the most notorious antiretroviral for causing nephrolithiasis, with crystalluria occurring in 20% of treated patients and symptomatic stones being a major side effect 2
• Indinavir stones form due to pH-dependent solubility in urine, with risk factors including low lean-body mass, doses of 1000 mg twice daily, and concomitant trimethoprim-sulfamethoxazole use 2
• Ritonavir-boosted indinavir regimens increase nephrolithiasis risk through higher peak drug concentrations 2
• Atazanavir and other protease inhibitors are among the most frequent causes of drug-induced calculi in HIV patients 3

Antibiotics and Antimicrobials

• Sulfonamides (including trimethoprim-sulfamethoxazole and sulfadiazine) cause intratubular crystal precipitation leading to acute renal failure, particularly sulfadiazine used for cerebral toxoplasmosis 2, 3
• Ceftriaxone can induce nephrolithiasis, especially with high doses or long-term treatment 3
• Ciprofloxacin causes intratubular crystal precipitation; avoidance of rapid intravenous bolus and adequate hydration are essential 2

Antivirals

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

Carbonic Anhydrase Inhibitors

• Acetazolamide and topiramate provoke metabolically-induced calculi by altering urinary pH and calcium/phosphate excretion 3
• These agents increase the risk of calcium phosphate stone formation through urinary alkalinization 3

Metabolic Disruptors

Calcium and Vitamin D Supplements

• Calcium supplements (as opposed to dietary calcium) increase stone risk through metabolic effects 1, 3
• Uncontrolled calcium/vitamin D supplements cause metabolically-induced calculi, with incidence likely underestimated 3

Other Medications

• Ephedrine-containing preparations may induce nephrolithiasis with high doses or long-term use 3
• Certain diuretics alter renal blood flow and intrarenal hemodynamics, potentially affecting stone risk 1

Critical Prevention Strategies

Hydration Requirements

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

Medication-Specific Precautions

• Avoid rapid intravenous bolus administration of acyclovir, ciprofloxacin, and foscarnet 2
• Adjust doses for renal dysfunction in patients receiving potentially nephrotoxic medications 2
• Monitor for crystalluria in patients taking indinavir, with urinalysis showing pyuria even without visible crystals 2

Monitoring and Risk Assessment

• Monitor high-risk patients more closely with periodic urinalysis and imaging 1
• Environmental conditions (temperature, atmospheric pressure, humidity) affect indinavir nephrolithiasis risk 2
• Coinfection with hepatitis B or C increases risk of indinavir-related stones 2

Common Pitfalls

• Failing to recognize drug-induced stones: Physical methods including infrared spectroscopy or X-ray diffraction are needed to demonstrate drug presence within calculi 3
• Underestimating metabolically-induced calculi: Careful clinical inquiry is essential to differentiate these from common stones, as their incidence is probably underestimated 3
• Inadequate hydration counseling: Approximately 20 different molecules can induce nephrolithiasis, making hydration counseling critical for all at-risk patients 3