Safety 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 nephropathy, 63 hypertensive patients with thiazide-induced asymptomatic hyperuricemia (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 hydrochlorothiazide (HCTZ) 50 mg q.d., HCTZ 50 mg q.d., or placebo for three weeks. To potentiate 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/creatinine, were not reported. Uric acid excretion and urine pH increased four and 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 hours on day 1 compared with day 0 associated with the concurrent rise in urine pH. Day 7 and 21 changes, compared with day 0, in uric acid excretion rate, urine pH, and dihydrogen urate with losartan were comparable to day 1 results but were not statistically significant. Serum uric acid was significantly reduced after 21 days of therapy with losartan.


CONCLUSIONS
Losartan decreased serum uric acid and increased uric acid excretion without increasing urinary dihydrogen urate, the primary risk factor for acute urate nephropathy, during 21 days of dosing in hypertensive patients with thiazide-induced hyperuricemia.
Shahinfar
S
S
University of Chicago, Illinois, USA. ShahnazvShahinfar@merck.com
Simpson
R L
RL
Carides
A D
AD
Thiyagarajan
B
B
Nakagawa
Y
Y
Umans
J G
JG
Parks
J H
JH
Coe
F L
FL
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects*; D001581:Benzothiadiazines; D004232:Diuretics; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D019808:Losartan / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects*; D014527:Uric Acid / Q000097:blood*
D000959:Antihypertensive Agents; D001581:Benzothiadiazines; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D014527:Uric Acid; D019808:Losartan