Symptomatic Crystalluria Associated with Indinavir

OBJECTIVE: To report a case of severe and recurrent crystalluria resulting from the use of indinavir and to review the literature describing this adverse effect. CASE SUMMARY: A 26-year-old HIV-positive white woman had recurrent episodes of left-sided flank pain accompanied by dilation of the left renal collecting system while undergoing treatment with a triple-drug regimen including indinavir 1200 mg every 12 hours (full dosage). Typical indinavir crystalluria was observed, with no evidence of stones. Acute episodes were treated with intravenous fluids, diclofenac, and ciprofloxacin. Crystalluria and clinical symptoms eventually resolved with withdrawal of indinavir and substitution with a different protease inhibitor. Renal function remained normal. DISCUSSION: A wide spectrum of disorders of the urinary tract can occur in subjects taking indinavir, with potentially severe complications caused by crystalluria and stones. Indinavir is excreted in the urine; the low solubility of those crystals is the critical factor accounting for the risk of stone formation. An elevated pH with a reduced excretion of citric acid contributes to the low urinary solubility of indinavir. Pharmacokinetic interactions with other drugs, leading to elevated plasma concentrations of indinavir, and dehydration could also increase the risk of stone formation. The impact on renal function can be unfavorable over the long-term period. Cornerstones of treatment and prevention are increased fluid intake and possibly urinary acidification. Emergency drainage may be required for patients with severe obstruction. Reducing the dosage of indinavir has been proposed, but this carries the risk of viral mutations with development of resistance. CONCLUSIONS: Treatment with indinavir can result in crystalluria with potentially severe obstruction. All patients taking indinavir, not only those with documented crystalluria or renal effects from the drug, should greatly increase their fluid intake and have renal function checked at baseline and then monitored regularly. Urinalysis also should be performed regularly for appropriate monitoring and prevention.