Safely of losartan in hypertensive patients with thiazide-induced hyperuricemia

Background. Losartan, an angiotensin II receptor antagonist, has been shown to decrease serum uric acid and to increase urinary excretion of uric acid . Methods. To determine if this effect can increase the risk of acute urate n ephropathy, 63 hypertensive patients with thiazide-induced asymptomatic hyp eruricemia (serum uric acid 7.0 to 12.0 mg/dl) were randomized double-blind to losartan 50 mg every day (q.d.), losartan 50 mg plus hydrochlorothiazid e (HCTZ) 50 mg q.d., HCTZ 50 mg q.d., or placebo for three weeks. To potent iate the risk of crystal formation, patients received a 2 g/kg protein diet one day prior to each clinic visit on days 0 (baseline), 1, 7, and 21. Results. Adverse events typically associated with acute urate nephropathy. for example, flank pain, hematuria, or increased blood urea nitrogen/creati nine, were not reported. Uric acid excretion and urine DH increased four an d six hours after losartan on day 1 compared with day 0. Dihydrogen urate, the primary risk factor for crystal formation, decreased at four and six ho urs on day 1 compared with day 0 associated with the concurrent rise in uri ne pH. Day 7 and 21 changes, compared with day 0? in uric acid excretion ra te, urine pH, and dihydrogen urate with losartan were comparable to day 1 r esults but were not statistically significant. Serum uric acid was signific antly reduced after ii days of therapy with losartan. Conclusion. Losartan decreased serum uric acid and increased uric acid excr etion without increasing urinary dihydro gen urate, the primary risk factor for acute urate nephropathy, during 21 days of dosing in hypertensive pati ents with thiazide-induced hyperuricemia.