Literature review ARB monotherapy Rayner and colleagues conducted an open-label, randomized, controlled, two-parallel group study [ Rayner et al. In the study, 59 patients were enrolled to receive either losartan 50— mg daily or candesartan 8—16 mg daily for 24 weeks. Individuals had to be maintained on a stable dose of diuretics for at least 12 weeks before study entry. Those with baseline use of steroids, NSAIDs, allopurinol, colchicine or with renal dysfunction were excluded.
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Abstract Background The angiotensin receptor blocker losartan inhibited urate transporter 1 URAT1 according to in vitro experiments. However, it is still unknown whether the inhibitory effect of losartan on URAT1 contributes to its uricosuric action in humans. Methods Thirty-two patients with hypertension and nine patients with idiopathic renal hypouricemia five with and four without hypertension were enrolled for this study.
Before and after 1-month treatment, the serum concentration of urate Sur and creatinine Scr , and the clearance value of urate Cur and creatinine Ccr were determined. Results Blood pressure BP significantly decreased in the patients treated with either losartan or candesartan.
The lack of effect of URAT1 inhibitors on renal excretion of urate was independent of the renal function of hypouricemic patients. Conclusions These findings suggested that losartan inhibited URAT1 and thereby it lowered Sur levels in hypertensive patients. The angiotensin II receptor blocker losartan lowers serum concentration of urate Sur in hypertensive subjects through a significant uricosuric action.
Exercise-induced acute renal failure and nephrolithiasis have been reported as complications of hypouricemia. Second, we examined the effect of losartan and benzbromarone on urinary urate excretion in hypertensive patients with idiopathic hypouricemia with homozygote and compound heterozygote of loss-of-function mutations of URAT1. Methods Patients and clearance study in hypertensive patients. Thirty-two untreated hypertensive outpatients 66 years old on average, 24 males attending Tottori University Hospital, Shinsei Hospital, and Nosaka Clinic Yonago, Japan were enrolled for this study.
None of them had gout or urinary calculi, or were they under treatment with oral antidiabetic agents, nonsteroidal anti-inflammatory drugs or fibrates. All the procedures carried out in this study were in accordance with the Helsinki Declaration of as revised in All patients provided written informed consent for their participation in the study whose protocol had been authorized by the ethical committee of Tottori University.
Clinic BP was measured using a mercury sphygmomanometer and a cuff of appropriate size in accordance with the American Heart Association Committee on Blood Pressure Determination. After the patient sat for 5 min, BP was measured three times at 1—2- min intervals, and the mean value was taken as the average BP for that visit. The two treatment groups were comparable in terms of age, BMI, weight, height, baseline sitting BP, fasting plasma glucose levels, serum levels of total cholesterol, and triglycerides.
Urine samples were collected from to AM and venous blood sample was drawn halfway through each clearance period before and after 1-month treatment; Sur, urine levels of urate, as well as serum and urine levels of creatinine Scr and Ucr, respectively were promptly determined.
Renal clearance for urate Cur and creatinine Ccr was determined as described elsewhere. Five hypertensive outpatients with idiopathic renal hypouricemia 49 years old on average, three men and four normotensive outpatients with idiopathic renal hypouricemia all women whose average age was 56 were enrolled for this study.
These patients were unrelated and provided written informed consent for the study. A month after the benzbromarone test, the patients received 50 mg oral losartan and the same measurements were taken.
Eight hypertensive subjects carrying the wild URAT1 gene matched for age and gender with five hypertensive hypouricemia patients were subjected to the benzbromarone and losartan tests. To estimate the validity of a single period for the clearance test, we conducted probenecid and losartan loading tests in hypertensive case no. The phase before the administration of the drug consisted of a single-clearance period of 30 min.
A venous blood sample was drawn halfway through each clearance phase. Two-way analysis of variance with repeated measures was performed to analyze the effects of losartan and candesartan. There were no statistical differences in the pre- and postadministration values between the two groups. All patients carried the wild-type SLC22A12 gene. There were no statistical differences in the baseline values of Scr 0. Losartan induced a significant reduction in Sur 6. Losartan induced a significant increase in Cur 4.
However, candesartan did not influence Cur 5. Because changes in renal excretion of urate induced by angiotensin receptor blockers might be influenced by renal adaptation during their administration, we reexamined the acute effects of candesartan before and 2 h after its administration on renal excretion of urate. Candesartan did not influence Sur 5. Clinical characteristics and URAT1 genes in hypertensive and normotensive patients with idiopathic renal hypouricemia Table 1 summarizes the SLC22A12 genes and clinical characteristics of five hypertensive patients and four normotensive patients with idiopathic renal hypouricemia.
These findings were compatible with the diagnosis of idiopathic renal hypouricemia. Except for CA, all other mutations were previously reported to be loss-of-function mutations. Case no. Table 1.
The effect of angiotensin II receptor blockers on hyperuricemia
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