Association of plasma uric acid with ischaemic heart disease and blood pressure: mendelian randomisation analysis of two large cohorts

Objectives: To assess the associations between both uric acid levels and hyperuricaemia, with ischaemic heart disease and blood pressure, and to explore the potentially confounding role of body mass index. Design: Mendelian randomisation analysis, using variation at specific genes (SLC2A9 (rs7442295) as an instrument for uric acid; and FTO (rs9939609), MC4R (rs17782313), and TMEM18 (rs6548238) for body mass index). Setting: Two large, prospective cohort studies in Denmark. Participants: We measured levels of uric acid and related covariables in 58 072 participants from the Copenhagen General Population Study and 10 602 from the Copenhagen City Heart Study, comprising 4890 and 2282 cases of ischaemic heart disease, respectively. Main outcome: Blood pressure and prospectively assessed ischaemic heart disease. Results: Estimates confirmed known observational associations between plasma uric acid and hyperuricaemia with risk of ischaemic heart disease and diastolic and systolic blood pressure. However, when using genotypic instruments for uric acid and hyperuricaemia, we saw no evidence for causal associations between uric acid, ischaemic heart disease, and blood pressure. We used genetic instruments to investigate body mass index as a potentially confounding factor in observational associations, and saw a causal effect on uric acid levels. Every four unit increase of body mass index saw a rise in uric acid of 0.03 mmol/L (95% confidence interval 0.02 to 0.04), and an increase in risk of hyperuricaemia of 7.5% (3.9% to 11.1%). Conclusion: By contrast with observational findings, there is no strong evidence for causal associations between uric acid and ischaemic heart disease or blood pressure. However, evidence supports a causal effect between body mass index and uric acid level and hyperuricaemia. This finding strongly suggests body mass index as a confounder in observational associations, and suggests a role for elevated body mass index or obesity in the development of uric acid related conditions

Antiepileptic drugs reduce serum uric acid

Uric acid examination in 554 epileptic out-patients under long-term anticonvulsant medication revealed significantly lower serum concentrations compared to a group of normal controls. In patients taking enzyme-inducing drugs, uric acid levels were found to be lower than in those under valproate sodium. In addition, uric acid concentrations showed a negative correlation with duration of therapy in epileptic males. At this time, we can only speculate on the mechanism involved in the reduction of uric acid by enzyme-inducing anticonvulsants as well as on the possible implication of this finding in the treatment of hyperuricemia

In vitro analysis of urinary stone composition in dual-energy computed tomography

Purpose: Dual energy computed tomography (DECT) is a new method of computed tomography (CT) imaging, allowing the assessment of not only the object's morphology, but also its composition. The aim of the study was to evaluate the potential of in vitro DECT evaluation of urinary stones' chemical composition. Material and methods: Six samples of surgically removed renal stones were scanned using DECT and analyzed by scanner vendor software. Uric acid stones were marked red and calcium stones white by the software. The real composition of the stones was finally verified using physicochemical laboratory analysis. Results: In 5 out of 6 samples, the composition of stones in DECT (3 samples identified as uric acid and 2 samples as calcium) was consistent with the physicochemical analysis (3 samples identified as uric acid, 1 as calcium phosphate, 1 as calcium oxalate). In DECT it was not possible to determine more precisely the type of calcium compounds (calcium phosphate vs. calcium oxalate) as established in the physicochemical analysis. In one stone identified in physicochemical analysis as uric acid, DECT detected a composite layered structure containing both uric acid and calcium compounds. Conclusions: DECT allows uric acid to be distinguished from calcium urinary tract stones, which is crucial in the choice of appropriate therapy. Using the available hardware and software, it was not possible to more accurately distinguish types of calcified stones. Evaluation of the stone type in DECT may be limited in the case of mixed chemical composition

Level of Serum Uric Acid in Pre-eclamptic and Normal Pregnant Women

Objective: The objective of study was to find out serum uric acid level in normal andpreeclamptic pregnant women of third trimester visiting outpatient department of obstetrics and gynecology of Bahawal Victoria Hospital, Bahawalpur. Methodology: It was a cross sectional descriptive study conducted form July 2018 to June 2019. All primigravida women of age 18-35 years in third trimester of singleton pregnancy attending in Obstetrics and Gynecology Outpatient Department of Bahawal Victoria Hospital in study duration were included in the study. Statistical analysis was performed by using SPSS version 14. Chi-square test was performed to find the statistical difference regarding uric acid distribution between groups and ‘p' value <0.05 was considered as a lowest level of significance. Results: Out of total 1212 women 84.6% were normal and 15.4% had preeclampsia. In our study out of 187 preeclamptic women, 63.6% had raised serum uric acid level and out of 268 normal pregnant women uric acid level was raised in only 39.5%. Results were found statistically significant. Conclusion: Results of our study suggest that serum uric acid level in pregnant women can be used as a useful and inexpensive marker in prediction of preeclampsia and preventive measures can be taken accordingly

Modeling Uric Acid Kidney Stones Disease in D. melanogaster using RNAi and Dietary Modulation

In humans, the major predictor for gout and forming uric acid kidney stones is elevated uric acid in the serum and urine respectively. It is known that uric acid is an end metabolite of purine degradation in humans, but in other species from D. melanogaster to lower apes, uric acid can be further metabolized by urate oxidase into readily excreted allantoin. We hypothesize that if urate oxidase enzyme activity and dietary purine are both critical in uric acid kidney stone formation, then urate oxidase knockdown in combination with dietary purine supplementation will increase uric acid and induce uric acid kidney stone formation in D. melanogaster. Initially, we confirmed urate oxidase knockdown and then elevation of uric acid as a consequence. We then confirmed uric acid kidney stones formed as a consequence of urate oxidase knocked down and a high purine diet. Next, we tested compounds used to treat gout or uric acid kidney stones in humans using our model. We found that allopurinol and potassium citrate reduced uric acid kidney stone formation in our model. We then tested whether compounds predicted to reduce uric acid and uric acid kidney stones in humans, but not currently used as treatments, can reduce uric acid kidney stone formation in our model. We found that methotrexate, hydrochlorothiazide, and l-lysine were effective at reducing uric acid kidney stone formation. Lastly, we ran a medium throughput screen of 117 natural compounds for inhibitors of uric acid kidney stone formation using our model and found seven inhibitors

Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid through inhibition of urate transporters in the kidney.

BackgroundExcess body burden of uric acid promotes gout. Diminished renal clearance of uric acid causes hyperuricemia in most patients with gout, and the renal urate transporter (URAT)1 is important for regulation of serum uric acid (sUA) levels. The URAT1 inhibitors probenecid and benzbromarone are used as gout therapies; however, their use is limited by drug-drug interactions and off-target toxicity, respectively. Here, we define the mechanism of action of lesinurad (Zurampic®; RDEA594), a novel URAT1 inhibitor, recently approved in the USA and Europe for treatment of chronic gout.MethodssUA levels, fractional excretion of uric acid (FEUA), lesinurad plasma levels, and urinary excretion of lesinurad were measured in healthy volunteers treated with lesinurad. In addition, lesinurad, probenecid, and benzbromarone were compared in vitro for effects on urate transporters and the organic anion transporters (OAT)1 and OAT3, changes in mitochondrial membrane potential, and human peroxisome proliferator-activated receptor gamma (PPARγ) activity.ResultsAfter 6 hours, a single 200-mg dose of lesinurad elevated FEUA 3.6-fold (p < 0.001) and reduced sUA levels by 33 % (p < 0.001). At concentrations achieved in the clinic, lesinurad inhibited activity of URAT1 and OAT4 in vitro, did not inhibit GLUT9, and had no effect on ABCG2. Lesinurad also showed a low risk for mitochondrial toxicity and PPARγ induction compared to benzbromarone. Unlike probenecid, lesinurad did not inhibit OAT1 or OAT3 in the clinical setting.ConclusionThe pharmacodynamic effects and in vitro activity of lesinurad are consistent with inhibition of URAT1 and OAT4, major apical transporters for uric acid. Lesinurad also has a favorable selectivity and safety profile, consistent with an important role in sUA-lowering therapy for patients with gout

Allopurinol use yields potentially beneficial effects on inflammatory indices in those with recent ischemic stroke: a randomized, double-blind, placebo-controlled trial

<p><b>Background and Purpose</b>: Elevated serum uric acid level is associated with poor outcome and increased risk of recurrent events after stroke. The xanthine oxidase inhibitor allopurinol lowers uric acid but also attenuates expression of inflammatory adhesion molecules in murine models, reduces oxidative stress in the vasculature, and improves endothelial function. We sought to investigate whether allopurinol alters expression of inflammatory markers after acute ischemic stroke.</p> <p><b>Methods</b>: We performed a randomized, double-blind, placebo-controlled trial to investigate the safety, tolerability, and effect of 6 weeks’ treatment with high- (300 mg once a day) or low- (100 mg once a day) dose allopurinol on levels of uric acid and circulating inflammatory markers after ischemic stroke.</p> <p><b>Results</b>: We enrolled 50 patients with acute ischemic stroke (17, 17, and 16 in the high, low, and placebo groups, respectively). Mean (±SD) age was 70 (±13) years. Groups had similar characteristics at baseline. There were no serious adverse events. Uric acid levels were significantly reduced at both 7 days and 6 weeks in the high-dose group (by 0.14 mmol/L at 6 weeks, P=0.002). Intercellular adhesion molecule-1 concentration (ng/mL) rose by 51.2 in the placebo group, rose slightly (by 10.6) in the low-dose allopurinol group, but fell in the high-dose group (by 2.6; difference between groups P=0.012, Kruskal-Wallis test).</p> <p><b>Conclusion</b>: Allopurinol treatment is well tolerated and attenuates the rise in intercellular adhesion molecule-1 levels seen after stroke. Uric acid levels were lowered with high doses. These findings support further evaluation of allopurinol as a preventive measure after stroke.</p&gt

Hubungan Indeks Massa Tubuh Dengan Kadar Asam Urat Darah Pada Penduduk Desa Banjaranyar Kecamatan Sokaraja Kabupaten Banyumas

Uric acid is a weak acid that distributed throughout the extracellular fluid as a sodium urate . The amount of uric acid on the blood is influenced by dietary intake of purines, uric acid biosynthesis of the body and rate of uric acid excretion. Indonesian had nutrient problems on the globalization, where human lifestyle and meal pattern have canged. The result of body mass index of survey on the 1995-1997 at the 27 of province show that prevalence of obessity is 6,8% on man and 13,5% on woman.The aim this study was to know the correlation between body mass index with blood uric acid levels of the society Banjaranyar Sokaraja of Banyumas. The cross sectional study used to assess body mass index, and blood uric acid in 52 respondent that fulfill in inclution criteria. Sample research taken by simple random sampling.The average of body mass index and blood uric acid were normal cathegory, it was 27 respondent (51,92%), and normal blood uric acid levels cathegory was 41 respondent (78,85%). The correlation between body mass index with blood uric acid levels on man was r=-0,09 with p=0,70>?=0,05 and on woman was r=0,05 with p=0,80>?=0,05. There was no correlation between body mass index with blood uric acid levels of the society Banjaranyar Sokaraja Banyumas

Establishment of sex difference in circulating uric acid is associated with higher testosterone and lower sex hormone-binding globulin in adolescent boys

Men have higher circulating levels of uric acid than women. This sex difference is suspected to be a result of suppressive effects of estradiol on uric acid. If so, estradiol would be inversely associated with circulating uric acid. This study aimed to test this hypothesis. This cross-sectional study included 9472 participants (weighted sample size of 184,342,210) aged 12–80 years from the 2013 to 2016 US National Health and Nutrition Examination Survey. Associations of sex hormones with uric acid were analyzed using weighted least squares regression, adjusting for demographic characteristics, lifestyle risk factors, and comorbidities. Neither free nor bioavailable estradiol was inversely associated with circulating uric acid in adolescent boys or girls, or adult men or women, or perimenopausal women after full adjustment. The sex difference in uric acid was established during adolescence as a result of a dramatic increase in uric acid in adolescent boys. During adolescence, the increase in estradiol in girls over time was accompanied by a relatively unchanged level of uric acid. All three fractions of estradiol (free, bioavailable, and total) were positively associated with uric acid in adolescent boys and girls after full adjustment. In adolescent boys, all three fractions of testosterone were positively associated with serum uric acid, and sex hormone-binding globulin was inversely associated with uric acid after full adjustment. These results suggest that estradiol is not inversely associated with circulating uric acid in adolescents and the establishment of sex difference in circulating uric acid during adolescence is associated with higher testosterone and lower sex hormone-binding globulin in adolescent boys. © 2021, The Author(s)