Effect of Losartan or Eprosartan on Fructose Hyperuricemia

• Status: Completed
• Trial end date: 2010-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Hyperuricemia is seen in about 20% of adults in the general population, Chronic hyperuricemia, frequently manifesting as the gout, is a well-known risk factor of joint damage but has been also linked to a variety of other pathologies mostly affecting the cardiovascular system. The close relation between high uric acid concentration and increased risk of cardiovascular disease has been reported for more than a century. Furthermore, many studies reported a strong association between hyperuricemia, arterial hypertension, obesity and cardiovascular diseases even in an absence of typical clinical manifestations of gout.

Several studies showed that the prevalence of hyperuricemia in patients with hypertension is much higher than in the general population and may worsen after the onset of antihypertensive treatment. That may indicate that hyperuricemia may be also caused by antihypertensive drugs. In contrast to diuretics and nonselective beta blockers the agents that block the renin-angiotensin-aldosterone system have had a neutral effect on serum uric acid. Several clinical studies showed that losartan in contrast to other AT1-receptor agonists, may have specific uricosuric properties and thereby can lower uric acid concentration. It has been speculated that uricosuric effect could make losartan particularly useful for the treatment of arterial hypertension associated with hyperuricemia and metabolic syndrome.

The uricosuric effect of losartan is most likely due to overlapping two different mechanisms regulating the excretion of uric acid. Losartan may increase uric acid tubular secretion in the same way as other inhibitors of the renin-angiotensin-aldosterone system, but in addition it may specifically inhibit post-secretory resorption of uric acid in the proximal tubule. The effect may be due to a specific structure of the losartan molecule. The urateanion transporter is a monoammonium selective transporter, and the losartan molecule is mainly a monoanion at normal pH range (as opposed to dianion e.g. eprosartan) and therefore is a good substrate for the exchanger. However, this concept remains speculative since, e.g. irbesartan which is also a monoanion has no consistent uricosuric effect.

Fructose, in contrast to other carbohydrates causes an increase of serum uric acid concentration, which may facilitate the development of the metabolic syndrome.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Medical University of Lodz
• Treatments: Eprosartan; Losartan

Criteria

Inclusion Criteria:

• Age 18 years old

• Fulfillment of three or more of the AHA / NHLBI 2005 assessment criteria for the metabolic syndrome:

• abdominal obesity (i.e. handling in women ≥88 cm) male ≥ 102 cm

• concentration of triglycerides in the form ≥150 mg / dl

• concentration of HDL fraction (men <40 mg / dL, women <50 mg / dL)

• blood pressure ≥ 130/85 mmHg

• Correction of fasting glucose ≥100 mg / dL)

• Written and informed consent to participate in the case of

Exclusion Criteria:

• Congenital defects in fructose metabolism (hereditary fructose intolerance and idiopathic fructosuria)

• Mental illness, dementia

• Insufficient cooperation with the patient, non-compliance with doctor's recommendations

• Pregnancy

• Bilateral renal artery stenosis or stenosis to a solitary kidney and other contraindications for angiotensin receptor antagonists

• Chronic use of uricosuric drugs, xanthine oxidase inhibitors and AT1 receptor inhibitors