title: Beneficial effect of switching from a combination of angiotensin II receptor blockers other than losartan and thiazides to a fixed dose of losartan/hydrochlorothiazide on uric acid metabolism in hypertensive patients.
abstract: Among the angiotensin II receptor blockers (ARBs), losartan (LOS) has uricosuric action. The clinical benefits of LOS compared with those of other ARBs may be apparent when it is combined with diuretics, which have an unfavorable influence on serum uric acid (SUA). The effects of switching from combinations of ARBs other than LOS and thiazides to a fixed-dose combination comprising 50 mg LOS and 12.5 mg hydrochlorothiazide on blood pressure (BP), SUA, percent fractional excretion of UA (FEUA), and urine pH were assessed in 57 hypertensive outpatients. A significant reduction in BP was observed after 6 months (P < .01). The switching therapy significantly decreased SUA level (6.0 ± 1.3 vs. 5.7 ± 1.3 mg/dL, P < .01), which was accompanied by increases in FEUA (P < .01) and urine pH (P < .01). The change in SUA was negatively correlated with the changes in FEUA (P < .004) and estimated glomerular filtration rate (P < .05). The change in FEUA was positively correlated with the changes in urine pH (P < .05) but not with BP or estimated glomerular filtration rate. In a separate group of patients treated with ARBs other than LOS (n = 82), a significant BP reduction was observed, but no change in SUA or FEUA was observed. In conclusion, switching therapy decreased SUA level, which was accompanied by an increase in FEUA. This result may depend on the balance between LOS-induced inhibitory action of urate transporter 1 and hydrochlorothiazide-induced plasma volume reduction. The increase in urine pH plays a role in UA urinary excretion.
authors.affiliation: Department of Cardiovascular Medicine, Nephrology and Neurology, School of Medicine, University of the Ryukyus, Nishihara-cho, Okinawa, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ohshiro
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sakima
authors.forename: Seigo
authors.initials: S
authors.lastname: Nakada
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kohagura
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamazato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tana
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohya
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage* / Q000009:adverse effects; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D033461:Hyperuricemia / Q000139:chemically induced* / Q000652:urine; D019808:Losartan / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D016896:Treatment Outcome; D014527:Uric Acid / Q000652:urine*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; D006852:Hydrochlorothiazide; D014527:Uric Acid; D019808:Losartan