Crystalluria and urinary tract abnormalities associated with indinavir

Background: Indinavir, a protease inhibitor widely used to treat patients with HIV infection, has been associated with nephrolithiasis. Distinctive urinary crystals and a spectrum of urologic disorders were noted in patients receiving indinavir. Objective: To determine the composition of urinary crystals and the frequency of asymptomatic crystalluria and urinary tract symptoms in patients receiving indinavir. Patients: Patients with HIV infection who were enrolled in studies conducted at the National Institutes of Health. Measurements: Microscopic urinalysis, high-performance liquid chromatography (HPLC) and mass spectrometry of urinary crystals and stones, and clinical evaluation of patients with urologic symptoms. Results: Of 240 patients receiving indinavir, 142 provided urine specimens for analysis. Twenty-nine (20%) had crystals consisting of plate-like rectangles and fan-shaped or starburst forms. Mass spectrometry and HPLC confirmed that these crystals were composed of indinavir. OF 40 patients who were not receiving indinavir, none had similar crystals (P < 0.001). Nineteen of the 240 patients receiving indinavir (8%) developed urologic symptoms. Of these, 7 (3%) had nephrolithiasis and the other 12 (5%) had previously undescribed syndromes: crystalluria associated with dysuria and crystalluria associated with back or flank pain. Four of the patients with the latter syndrome had radiographic evidence of intrarenal sludging. Conclusions: Indinavir forms characteristic crystals in the urine. This crystalluria may be associated with dysuria and urinary frequency, with flank or back pain associated with intrarenal sludging, and with the classic syndrome of renal colic.