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.

Survey on uric acid in Chinese subjects with essential hypertension (SUCCESS): a nationwide cross-sectional study

“…Other antihypertensive drugs including amlodipine and diuretics did not significantly increase the risk of HUA. Previous literature showed that losartan, an ARB, could promote UA excretion, thereby reducing UA levels (9,10). Except for losartan, other ARBs did not show definite UA-lowering effects (26).…”

“…Big data on the prevalence of HUA in Chinese hypertensive patients are lacking. In addition, previous studies revealed that thiazide diuretics increased the serum UA level (8), while angiotensin II receptor blocker (ARB) losartan decreased the UA level to some degree (9,10), which indicated the contrasting effects of different antihypertensive agents on UA. However, these effects must be evaluated in a larger hypertensive population.…”

URAT1 Gene Polymorphisms Influence Uricosuric Action of Losartan in Hypertensive Patients with Hyperuricemia

“…It has been shown that losartan, not other ARBs, has a beneficial effect to reduce serum uric acid levels in several studies [24][25][26]. It seemed obvious that losartan was effective to reduce serum uric acid levels in the patients with higher serum uric acid levels.…”