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Safety of losartan in hypertensive patients with thiazide-induced hyperuricemia
S Shahinfar1, R L Simpson, A D Carides
1University of Chicago, Illinois, USA. ShahnazvShahinfar@merck.com
Insights
Losartan lowers uric acid levels and increases its excretion in hypertensive patients with hyperuricemia. This study found no increased risk of acute urate nephropathy, suggesting a safe profile for managing uric acid levels.
Area of Science:
- Nephrology
- Pharmacology
- Cardiovascular Medicine
Background:
- Losartan, an angiotensin II receptor antagonist, reduces serum uric acid and enhances urinary uric acid excretion.
- Thiazide diuretics can induce asymptomatic hyperuricemia in hypertensive patients.
Purpose of the Study:
- To evaluate the risk of acute urate nephropathy in hypertensive patients with thiazide-induced hyperuricemia treated with losartan.
- To assess the effect of losartan on uric acid metabolism and urine chemistry.
Main Methods:
- A randomized, double-blind study involving 63 hypertensive patients with hyperuricemia.
- Patients were assigned to losartan, losartan plus hydrochlorothiazide (HCTZ), HCTZ alone, or placebo for three weeks.
- A high-protein diet was administered to potentiate urate crystal formation risk.
Main Results:
- No adverse events associated with acute urate nephropathy were reported.
- Losartan increased uric acid excretion and urine pH, while decreasing dihydrogen urate.
- Serum uric acid levels were significantly reduced after 21 days of losartan therapy.
Conclusions:
- Losartan effectively lowers serum uric acid and increases uric acid excretion in hypertensive patients with hyperuricemia.
- Treatment with losartan did not elevate urinary dihydrogen urate, mitigating the primary risk factor for acute urate nephropathy.
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.
Conclusion:
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.