Urolithiasis associated with protease inhibitors

Abstract

Objective: We evaluated the radiographic characteristics as well as the clinical management of urolithiasis induced by systemic therapy with indinavir sulfate, a protease inhibitor utilized in the treatment of HIV infection.

Patients and methods: Fifteen consecutive HIV-positive male patients (average age 41.3 years) who presented with urolithiasis while being treated with indinavir sulfate (average time 11.1 months) were studied.

Results: All patients presented with flank pain, and eight had gross hematuria. All but one patient had microscopic hematuria. The location of the stones was the kidney in three, the proximal ureter in four, and the distal ureter in nine. One patient had both a renal and a proximal ureteral stone. The stones were radiolucent on CT imaging in five patients and could not be seen in five. In the five cases in which a stone was not definitely identified, a diagnosis of urolithiasis was established on the basis of ureteral obstruction and periureteral/renal streaking noted on CT. Treatment included observation with hydration in eight patients, ureteral stent placement in two patients, ureteroscopy in three patients, and extracorporeal shockwave lithotripsy in two patients. Stones were analyzed in five patients and proved to be 100% indinavir in three and a mixture of indinavir, calcium oxalate monohydrate, and calcium oxalate dihydrate in two.

Conclusions: Urolithiasis is a recognized complication of treatment with indinavir sulfate. Pure indinavir stones cannot be seen on CT unless intravenous contrast medium is utilized. Mixed calcium and indinavir stones can occur and may be radiopaque. The majority of HIV-positive patients with symptomatic urolithiasis can be treated conservatively with hydration. Metabolic evaluation of these patients with identification and correction of factors predisposing to stone formation may minimize future recurrences. Administration of this effective medication thus can continue uninterrupted.