Subject: CIPROFLOXACIN INDUCED CRYSTALLURIA AND STONE FORMATION

BILATERAL HYDRONEPHROSIS FROM CIPROFLOXACIN INDUCED CRYSTALLURIA AND STONE FORMATION

NAGESH CHOPRA*; PAUL L. FINE; BARBARA PRICE; IAN ATLAS

THE JOURNAL OF UROLOGY 2000;164:438

Ciprofloxacin is a widely used fluoroquinolone for the treatment of complicated and uncomplicated infections. Experimental studies in humans and animals have indicated that crystalluria may be associated with the administration of fluoroquinolones but, to our knowledge, no case of obstructive uropathy has been reported. We describe a case of bilateral urinary tract obstruction and acute renal failure due to urinary tract stones predominantly composed of ciprofloxacin.

CASE REPORT A 71-year-old white woman was admitted to the hospital with a 2-week history of intermittent gross hematuria, bilateral lower extremity edema and respiratory distress. Medical history was remarkable for deforming rheumatoid arthritis and moderate left ventricular dysfunction. Lower extremity deep vein thrombosis had been diagnosed two months earlier and warfarin sodium anticoagulation was prescribed. There was no history of azotemia, proteinuria, hematuria or nephrolithiasis. Symptoms of dysuria had developed 3 weeks earlier and 500 mg. ciprofloxacin were given orally twice daily for a total of 24 days for presumed urinary tract infection. Physical examination revealed an elderly white woman with diffuse expiratory wheezes and bilateral lower extremity edema. Creatinine was 3.1 mg./dl. (normal 0.6 to 1.4), uric acid 10.5 mg./dl. (normal 2.3 to 6.0) and urine pH 6.0 (normal 4.5 to 8.0). Grossly, urine contained copious gray sediment. Microscopically, a large number of crystals of varying morphology were present. A renal sonogram revealed normal size kidneys of normal echogenicity with bilateral hydronephrosis and 24- hour urine uric acid was 568 mg. (normal 250 to 750). Cystoscopy with bilateral retrograde pyelography and stent placement were performed. A large amount of friable crystalline material was present in the bladder and multiple radiolucent filling defects were identified in the distal ureters bilaterally. A specimen of the friable calculus was composed of 15% uric acid and 85% ciprofloxacin. Intravenous hydration was maintained and allopurinol was started. The urine sediment cleared rapidly, renal function returned to previous baseline levels and serum creatinine decreased to 0.7 mg./dl. within 72 hours. Retrograde pyelography shows multiple radiolucent filling defects bilaterally in distal ureters later discovered to be crystalline material largely composed of ciprofloxacin. DISCUSSION Ciprofloxacin induced crystalluria is well documented in animals. It is nearly insoluble at neutral or alkaline pH and crystallizes in the excreted alkaline urine in the species studied. Effects of urinary pH and hydration on ciprofloxacin induced crystalluria were studied in humans by Thorsteinsson et al.They concluded that ciprofloxacin may cause crystalluria when the urine pH is greater than 7., especially when higher doses, for example 1,000 mg., are used. Crystalluria is rare with urine pH less than 6.8. Based on clinical investigations in more than 4,000 patients, there is no evidence that ciprofloxacin leads to urolithiasis or adversely influences renal function. In a large series of 1,556 courses of ciprofloxacin Schacht et al reported no evidence of nephrotoxicity and no crystalluria.3 Our patient presented with bilateral ureteral obstruction due to calculi largely composed of ciprofloxacin. Obstructive crystalluria developed following a course of ciprofloxacin at standard dosages in the setting of acidic urine, which is a result not anticipated by prior reports of experimental and clinical ciprofloxacin induced crystalluria. We postulate that the uric acid crystals in the calculus material may have provided a nidus for ciprofloxacin crystal precipitation. We recommend that flouroquinolone crystalluria be considered when patients on quinolone therapy have crystalluria.