Drug-Induced Kidney Stones

Drug induced kidney stones form either from the drug or its metabolite crystallising in urine, or from a drug that alters urine chemistry to favour stone formation.

• Drugs that crystallise: indinavir, atazanavir (and, rarely, darunavir), sulfadiazine, sulfamethoxazole, triamterene, ceftriaxone (children, biliary and renal sludge), ciprofloxacin (alkaline urine), aciclovir (intravenous high dose), methotrexate, magnesium trisilicate, guaifenesin and ephedrine metabolites, allopurinol (xanthine), and ascorbic acid at high dose.
• Drugs that promote stones: topiramate and acetazolamide (alkaline urine, low citrate), loop diuretics (calciuria), calcium and vitamin D supplements, calcium-containing antacids (milk alkali), laxative abuse (ammonium urate), glucocorticoids, theophylline, antiretroviral drugs (HIV nephrolithiasis).
• HIV treatment is a large contributor in Kenya.

Renal colic, flank pain, haematuria, dysuria, sterile pyuria, urinary frequency, oliguria or acute kidney injury with crystalluria.

• Radiolucent stones (indinavir, atazanavir, xanthine, triamterene) may not appear on plain radiographs.
• Infants on ceftriaxone develop biliary pseudolithiasis and rarely renal stones.
• Differential diagnosis: metabolic stones (calcium oxalate, uric acid), infection stones, tumour, blood clot, papillary necrosis, interstitial nephritis from the same drug.
• Complications: obstruction, acute kidney injury, infection, chronic kidney disease with long exposure, recurrent stones and loss of therapy options in HIV.

Detailed drug and supplement history including over-the-counter and herbal agents, dose and duration.

• Urinalysis and microscopy for crystals (needle-shaped, fan-shaped, birefringent), urine pH, creatinine and electrolytes.
• Non-contrast CT (indinavir and atazanavir stones can be invisible on CT; use ultrasound or contrast imaging to show hydronephrosis); ultrasound.
• Stone analysis by infrared spectroscopy or X-ray diffraction identifies drug composition.
• Metabolic evaluation (24-hour urine) for drugs promoting stones.

Supportive: stop or substitute the culprit drug where possible; fluids 2.5 to 3 L daily (more for indinavir); avoid triggers (excess vitamin C, calcium supplements without need).

Pharmacological

• HIV protease inhibitor stones: switch to a regimen without indinavir or atazanavir (for example dolutegravir 50 mg daily with tenofovir and lamivudine); temporary interruption is rarely needed; hydration for 48 hours.
• Sulfonamide crystals: alkalinise urine with sodium bicarbonate 1.3 g (15 mmol) three to four times daily to urine pH above 7, and ensure urine output above 2 L daily; use trimethoprim-sulfamethoxazole with hydration.
• Topiramate or acetazolamide stones: replace the drug; potassium citrate 30 to 60 mmol daily.
• Calcium and vitamin D excess: stop supplements; reduce calcium to dietary needs and check serum calcium.
• Ceftriaxone: stop the drug, hydrate, and use an alternative cephalosporin; pseudolithiasis resolves over weeks.
• Uric acid and xanthine stones: allopurinol dose adjustment, urine alkalinisation to pH 6.5, fluids.
• Analgesia: diclofenac 75 mg IM or paracetamol 1 g IV for colic.

Procedures: ureteric stent or percutaneous nephrostomy for obstruction; ureteroscopy with laser lithotripsy; shock wave lithotripsy is poor for soft drug stones; intravenous hydration for acute kidney injury.

Special groups: HIV (specialist input on antiretroviral changes), children (avoid ceftriaxone with calcium infusions, hydration), pregnancy (avoid fluoroquinolones and indinavir), chronic kidney disease (dose by eGFR).

Red flags: anuria, rising creatinine, urosepsis, solitary kidney.

Follow-up: renal function and ultrasound at 2 to 4 weeks after drug change; stone analysis; annual urine tests on long term risky drugs.