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Sartans and uric acid

 

Clinical bottom line

Sartan drugs do appear to lower uric acid levels. This has been tested in small numbers of patients. The clinical importance of the finding to patients with hypertension, or gout, or both is not yet known.


There is observational data suggesting that sartan drugs, particularly losartan, has an effect of lowering uric acid levels in blood. Experimental work shows that losartan (though not its active metabolite) competitively inhibits urate reabsorption in the renal proximal tubule. There are associations between gout and hypertension. High blood urate levels are found in about a quarter of patients with hypertension, and hypertension is present in about a third of patients with gout.

This review examines the three randomised trials found in May 2002. Information from other studies will be added to the site as it becomes available.

Patients with essential hypertension


Reference


JG Puig et al. Effect of eprosartan and losartan on uric acid metabolism in patients with essential hypertension. Journal of Hypertension 1999 17: 1033-1039.

Methods

This was a randomised double blind parallel group study in patients over 18 years old with mild to moderate essential hypertension (sitting diastolic hypertension 95-114 mmHg). Excluded were patients on treatments influencing uric acid metabolism. Patients could be newly diagnosed or previously treated.

There was a screening visit, a single blind placebo run in of 2-3 weeks, a double blind active treatment of four weeks, and a post treatment follow up visit after another 1-2 weeks. During treatment patients had either 600 mg once daily eposartan or 50 mg losartan. Patients were instructed to follow a purine restricted diet (less than 75 mg a day of purines) on the day before and after urine collection.

Results

Patients were mostly male, and their average age was 59 years. There were 30 patients in each group.

On eposartan, the initial mean uric acid was 417 µmol/L, with a fall of 20 µmol/L over four weeks.

On losartan, the initial mean uric acid was 393 µmol/L, with a fall of 23 µmol/L over four weeks.

Urinary uric acid excretion was significantly increased with losartan, but not eposartan.

Significant reductions in blood pressure were seen with both sartan drugs.

Patients with hyperuricaemia and gout


Reference


C Würzner et al. Comparative effects of losartan and ibresartan on serum uric acid in hypertensive patients with hyperuricaemia and gout. Journal of Hypertension 2001 19: 1855-1860.

Methods

This study randomised 13 patients with hypertension (above 140/90) and hyperuricaemia (serum uric acid >420 µmol/L without treatment). Most suffered from chronic gout. No allopurinol or treatments affecting uric acid metabolism were allowed during the trial.

There was an initial three week run in period on enalapril 20 mg a day, before randomisation to losartan 50 mg or ibesartan 150 mg once a day for four weeks. At week four, doses were doubled for a further four week period. Patients then crossed over to the alternate therapy with a wash out period of three weeks, again on enalapril 20 mg a day.

Results

Eleven of the 13 patients (mean age 59 years) had an episode of gout before treatment began. Three were treated for type-2 diabetes, and five received a lipid lowering drug.

Serum uric acid was significantly reduced by losartan (Figure 1) but not ibesartan (Figure 2). Doubling the dose made no real difference to the reduction in uric acid levels.

Figure 1: Losartan and uric acid


Figure 2: Ibesartan and uric acid


Acute attacks of gout occurred on eight occasions with losartan and eight with ibesartan.

Renal transplant patients on cyclosporin


Reference


A Schmidt et al. The effect of ACE inhibitor and angiotensin II receptor antagonist therapy on serum uric acid levels and potassium homeostasis in hypertensive renal transplant recipients treated with CsA. Nephrology Dialysis Transplant 2001 16: 1034-1037.

Methods

This was an open randomised crossover study in 13 hypertensive renal transplant recipients treated with cyclosporin A. The patients (12 male, mean age 58 years) received either losartan 50 mg or enalapril 10 mg for three weeks with a washout period of two weeks. All had mild hypertension (>140/90, <160/100). Two were on diuretics.

Results

There was a non-significant increase in uric acid (from 7.8 to 8.2 mg/100 mL, 460 to 484 µmol/L) with enalapril.

There was anon-significant decrease in uric acid (from 7.8 to 7.3 mg/100 mL, 460 to 430 µmol/L) with losartan.

Comment

The evidence is that losartan has an effect in lowering uric acid levels, as may some, but not all, other sartans. The size of reductions seen was of the order of 5% to 10%. The clinical implications for patients with gout or hypertension, or both, is still unclear.