Part 1. Uric acid and losartan.
OBJECTIVE
To characterize the mechanism and clinical impact of the angiotensin-receptor blocker losartan on both renal uric acid handling and thereby serum uric acid.


RESULTS
Losartan effect on serum uric acid has been demonstrated at various stages of renal failure including most recently observations obtained in end-stage renal disease patients. Other angiotensin-receptor blockers do not alter renal handling of uric acid. The uricosuria, which accompanies losartan administration, has not been associated with adverse renal consequences, in part, because of the increase in urinary pH that follows its administration.


CONCLUSIONS
Hyperuricemia is closely linked to both hypertension and cardiovascular disease. The development of hyperuricemia and its persistence are clearly renal processes. Likewise, the correction of hyperuricemia is often accomplished by increasing its renal excretion. A number of medications, by way of varying mechanisms, can alter renal urate handling and thereby influence serum uric acid values. Most recently, the angiotensin-receptor blocker losartan has been shown to reduce serum uric acid. The mechanism of this process relates to losartan alone and does not involve the E-3174 metabolite of this compound. This probenecid-like effect of losartan occurs shortly after drug administration, and is both transient and dose-dependent. This property of losartan, touted by some as a meaningful pharmacological distinction among the angiotensin-receptor blockers, remains to be proved, since, to date, the hypothesis that a reduction in serum uric acid alters the natural history of cardiovascular disease has not been formally tested.
Domenic A
DA
Sica
Anton C
AC
Schoolwerth
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001769:Blood / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology*; D014527:Uric Acid / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D014527:Uric Acid; D019808:Losartan