Changes In Serum Uric Acid Levels Research Articles

Uric acid, cognitive disorders, neurodegeneration

This article examines the role of uric acid (UA) in cognitive changes and neurodegeneration, focusing on its functions as an antioxidant and prooxidant. Research suggests that changes in serum UA levels may be associated with the development or delay of cognitive impairment, especially in the context of neurodegenerative diseases such as Alzheimer's disease. It was revealed that there is a relationship between the level of UA and the dynamics of cognitive functions, indicating the potential neuroprotective properties of UA. Particular attention is paid to the balance between the antioxidant and prooxidant properties of UA, which may play a key role in protecting neurons from damage. However, research results are not clear-cut, highlighting the need for further research to more fully understand the role of UA in cognitive processes. Determining the optimal serum UA level may be an important step in developing strategies for the prevention and treatment of cognitive impairment associated with neurodegeneration. Overall, these studies advance the understanding of the mechanisms underlying the interaction between uric acid metabolism and brain health.

Effect of Dapagliflozin on Serum Uric Acid Levels in Patients with Advanced Chronic Kidney Disease.

Objective Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which are hypoglycemic agents, have been shown to be cardioprotective through a variety of mechanisms, and the effect of lowering uric acid (UA) levels may be one of the mechanisms. In the present retrospective study, we investigated the changes in serum UA levels in patients with chronic kidney disease (CKD) treated with SGLT2 inhibitors. Methods We included 31 patients with CKD who were newly started on dapagliflozin for renal protection and evaluated trends in various parameters, including serum UA levels and UA excretion from urine. Results The patients' median age was 71 years old, 20 patients were men, 7 patients had diabetes, and the median estimated glomerular filtration rate was 33.9 mL/min/1.73 m2 (CKD stage 3: 21 cases, stage 4: 10 cases). The differences in UA and fractional excretion of UA after three weeks and three months of prescription showed significantly decreased UA values and an increased fractional excretion of UA. Conclusion Our findings suggest that dapagliflozin can lower serum UA levels via increased UA excretion, even in patients with advanced CKD.

Factors influencing the occurrence of hyperuricemia and poor cardiac and renal outcomes in chronic kidney disease.

The aim of our study was to analyze the factors influencing the occurrence of hyperuricemia and poor cardiac and renal outcomes in chronic kidney disease (CKD). One hundred and sixteen patients with CKD admitted to our hospital from January 2022 to September 2022 were picked as the subjects. Fasting venous blood of these subjects was collected to value the serum uric acid (SUA) levels on an automatic biochemical analyzer. Patients were then grouped as the CKD-only group (n=80) and hyperuricemia group (n=36), according to the SUA results, or the good prognosis group (n=88) and poor prognosis group (n=28), according to the presence of cardiovascular diseases. The changes in laboratory indexes and clinical data were analyzed and compared. Multivariate logistic regression analysis was used to analyze the risk factors for combined hyperuricemia and the risk factors for poor cardiac and renal outcomes in patients with CKD. The correlation between SUA level and cardiac and renal indexes was analyzed by Pearson analysis. Patients in the CKD hyperuricemia group had markedly higher content of systolic blood pressure (SBP), diastolic blood pressure (DBP), B-type natriuretic peptide (BNP), urinary retinol-binding protein (RBP), urinary N-acetyl-β-D glucosidase (NAG), much higher proportion of heart failure episodes history, and much lower content of total cholesterol (TC), albumin (Alb), hemoglobin (Hb), urinary α1-microglobulin (α1-MG), and glomerular filtration rate (eGFR) than the CKD-only group (p < 0.05). SUA, BNP, SBP, and history of heart failure episodes were independent risk factors for combined hyperuricemia in CKD patients (p < 0.05). Besides, eGFR, albumin, and hemoglobin were independent protective factors for combined hyperuricemia in CKD patients (p < 0.05). Compared with the good prognosis group, the content of BNP, SBP, DBP, urinary RBP, urinary NAG, and SUA was much higher, the proportion of heart failure episodes history was obviously higher, and the levels of Alb, Hb, TC, eGFR, and urinary α1-MG were sharply lower in the poor prognosis group (p < 0.05). SUA, BNP, SBP, and history of heart failure episodes were independent risk factors for poor cardiac and renal outcomes (p < 0.05), and eGFR was an independent protective factor for poor cardiac and renal outcomes in patients with CKD (p < 0.05). The SUA level in CKD patients was positively correlated with BNP and SBP (r=0.463, 0.215, p < 0.05), but negatively correlated with eGFR (r=0.463, 0.215, p < 0.05). The serum SUA level was elevated with the aggravation of the CKD stage. High serum SUA level is a risk factor for the development of hyperuricemia and poor cardio-renal outcomes in CKD patients, suggesting that early monitoring of changes in SUA levels may help assess the risk of cardio-renal outcomes in CKD patients.

GLUT9 as a potential drug target for chronic kidney disease: Drug target validation by a Mendelian randomization study.

Although chronic kidney disease (CKD) is recognized as a major public health concern, effective treatment strategies have yet to be developed. Identification and validation of drug targets are key issues in the development of therapeutic agents for CKD. Uric acid (UA), a major risk factor for gout, has also been suggested to be a risk factor for CKD, but the efficacy of existing urate-lowering therapies for CKD is controversial. We focused on five uric acid transporters (ABCG2, SLC17A1, SLC22A11, SLC22A12, SLC2A9) as potential drug targets and evaluated the causal association between serum UA levels and estimated glomerular filtration rate (eGFR) using single-SNP Mendelian Randomization. The results showed a causal association between genetically predicted changes in serum UA levels and eGFR when genetic variants were selected from the SLC2A9 locus. Estimation based on a loss-of-function mutation (rs16890979) showed that the changes in eGFR per unit increase in serum UA level was -0.0082 ml/min/1.73 m2 (95% CI -0.014 to -0.0025, P = 0.0051). These results indicate that SLC2A9 may be a novel drug target for CKD that preserves renal function through its urate-lowering effect.

The effect of dapagliflozin on uric acid excretion and serum uric acid level in advanced CKD

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) exhibit renoprotective effect in patients with chronic kidney disease (CKD) and reduce serum uric acid (UA) in patients with diabetes mellitus. However, it is not clarified whether SGLT2i reduce serum UA levels in patients with advanced CKD. This study aimed to investigate the impact of SGLT2i on change in serum UA levels in patients with advanced CKD. Data of 121 Japanese patients with CKD who were newly administered 10 mg dapagliflozin in our department between August 2021 and August 2022 were analyzed. Changes in UA and fractional excretion of UA (FEUA) were analyzed using multiple regression analysis. Of 75 patients, 21 (28.0%) patients, 24 (32.0%) patients, 29 (38.7%) patients, and 1 (1.3%) patient were categorized as having CKD stage 3a, 3b, 4, and 5, respectively. The median age was 67 years, and 72.0% were male. 23 (30.7%) of patients had diabetes mellitus. The median estimated glomerular filtration rate, serum UA, and FEUA were 35.7 mL/min/1.73 m2, 6.4 mg/dL, and 6.76%, respectively, at the time of dapagliflozin administration. After administration, serum UA decreased to 5.6 mg/dL and FEUA increased to 9.22%. Dapagliflozin increases FEUA and reduces serum UA levels in patients with advanced CKD.

A study of the relationship between serum uric acid levels and pain in patients with migraine.

Serum uric acid (SUA), the end product of purine metabolism acts as an antioxidant and is related to oxidative stress. It has been reported that SUA may be involved in the pathogenesis of neurodegenerative diseases including Alzheimer disease, Huntington disease, Parkinson disease, and multiple sclerosis. However, studies evaluating SUA levels in migraine are scarce. This study aimed to explore the relationship between pain characteristics and SUA levels in patients with migraine and compare SUA levels in migraine patients during a headache attack and headache-free period with those control groups. This prospective, cross-sectional study included 78 patients with migraine and 78 healthy subjects who were randomly selected from hospital personnel as the control group. Headache characteristics (duration of attack, pain intensity, and headache frequency) and sociodemographic features were recorded. The SUA level was measured once in the control group and twice in the migraine patients, during the migraine attack and headache-free periods. Although the SUA levels of the migraine group in the headache-free period were higher than those of the control group, the difference was not statistically significant. Gender was not significantly related to the change in SUA levels between the attack and headache-free period. When the correlation between age, duration of migraine, frequency, duration, and intensity of pain was evaluated; the difference between SUA levels in female migraine patients was weakly correlated with headache intensity, whereas male patients had a moderate correlation. (P < .05; R > 0.250, and R > 0.516, respectively). The difference in SUA level in the migraine attack period compared to the headache-free period showing a positive correlation with pain intensity suggested that SUA may have a role in migraine due to its antioxidant role.

EVALUATION OF SERUM URIC ACID, GLUCOSE AND OTHER GLYCEMIC PARAMETER IN TYPE II DIABETIC INDIVIDUALS

Background: In spite of antioxidant property serum uric acid (SUA) has a positive association with blood glucose. SUA is considered as a strong and an independent risk factor for diabetes but low serum level of uric acid has been reported in the hyperglycemic state. Diabetes mellitus is a metabolic disorder of multiple etiologies resulting from defect in insulin action. So, aim of this study is to assess whether there is any change in SUA level and to establish whether there is any association with type II diabetes mellitus (DM) or not. Methods: A cross sectional study was conducted in 264 cases of DM. SUA, fasting blood glucose (FBG), post-prandial blood glucose (PPBG) and glycated hemoglobin (HbA1c) level were measured. Pearson’s correlation was employed to calculate the ‘r’ value by using SPSS version 15. Results: In our study prevalence of hyperuricemia was 18.5%. Mean SUA in male and female was 5.95 mg/dl and 5.54 mg/dl respectively in DM. HbA1c has positive correlation with FBG and PPBG (r value = 0.720 and 0.775, respectively p=&lt;0.001), while SUA has negative correlation with HbA1c, FBG and PPBG (r value= -0.179, p =0.004, -0.070, p=0.257 and -0.078, p=-0.204 respectively.). Conclusions: SUA level is increased in DM. SUA was high among male and SUA initially increased when FBS and HbA1c increases then decreases as FBG and HbA1c level were further increased. SUA has negative correlation with FBG, PPBG and HbA1c, while HbA1c has a positive correlation with FBG and PPBG.

Washed microbiota transplantation reduces serum uric acid levels in patients with hyperuricaemia.

BACKGROUNDPrevious studies have found that hyperuricaemia (HUA) is closely related to intestinal flora imbalance.AIMThe current study investigated the effects and safety of washed microbiota transplantation (WMT) on serum uric acid (SUA) levels in different populations.METHODSA total of 144 patients who received WMT from July 2016 to April 2020 in the First Affiliated Hospital of Guangdong Pharmaceutical University and had SUA data before treatment were selected. Changes in SUA levels before and after treatment were retrospectively reviewed based on short-term and mid-term effects of WMT regimens. SUA levels measured in the last test within 3 mo after the first WMT represented the short-term effect, and SUA levels measured in the last test within 3-6 mo after the first WMT represented the mid-term effect. The patients were divided into an HUA group (SUA > 416 μM) and a normal uric acid (NUA) group (SUA ≥ 202 μM to ≤ 416 μM) based on pretreatment SUA levels.RESULTSAverage short-term SUA levels in the HUA group decreased after WMT (481.00 ± 99.85 vs 546.81 ± 109.64 μM, n = 32, P < 0.05) in 25/32 patients and returned to normal in 10/32 patients. The short-term level of SUA reduction after treatment moderately correlated with SUA levels before treatment (r = 0.549, R² = 0.300, P < 0.05). Average SUA levels decreased after the first and second courses of WMT (469.74 ± 97.68 vs 540.00 ± 107.16 μM, n = 35, and 465.57 ± 88.88 vs 513.19 ± 78.14 μM, n = 21, P < 0.05). Short-term and mid-term SUA levels after WMT and SUA levels after the first, second and third courses of WMT were similar to the levels before WMT in the NUA group (P > 0.05). Only 1/144 patients developed mild diarrhea after WMT.CONCLUSIONWMT reduces short-term SUA levels in patients with HUA with mild side effects but has no obvious effect on SUA levels in patients with NUA.

The Association between Baseline, Changes in Uric Acid, and Renal Failure in the Elderly Chinese Individuals: A Prospective Study with a 3-Year Follow-Up.

Objective The objective is to find whether serum uric acid (SUA) levels are associated with the progression of chronic kidney disease (CKD) remains uncertain, and follow-up data among the elderly population are relatively lacking, especially in China. The aim of the present study was to reveal the association between baseline SUA levels, changes in SUA levels, and renal failure in Chinese elderly adults. Methods In this retrospective cohort study, 425 subjects (age range 71–100 years) were analyzed and divided into quartiles based on baseline SUA levels (Q1: <4.8; Q2: <5.7; Q3: <6.5; and Q4: ≥6.5 mg/dl). CKD was defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. We used multiple linear and logistic regressions to compare the risk of renal dysfunction among the different SUA level groups. Results The prevalence of hyperuricemia was 24.24% in the elderly subjects. In the multivariable analysis, the odds ratio (OR) for the development of CKD increased with the increase in SUA quartiles at baseline (1.00 vs. 1.79 (95% CI, 1.00–3.22), 3.4 (95% CI, 1.79–6.47), and 6.79 (95% CI, 3.45–13.75), respectively; P for linear trend <0.001), and a per unit increase in baseline SUA levels gave an OR of 1.76 (95% CI, 1.45–2.14) for renal failure. At the same time, a change in SUA levels had a stronger inverse correlation with a change in eGFR in females (r = −0.318, P < 0.001) than in males (r = −0.187, P < 0.01). In a linear regression analysis, a 1 mg/dl increase in SUA levels was associated with an additional 1.25 (95% CI, −1.83 to −0.67) ml/min/1.73 m2 decrease in eGFR over a 3-year period. Conclusion Elevated baseline SUA levels and changes in SUA levels were associated with a decline in eGFR and an increased risk of CKD in an elderly Chinese population.

Changes of serum uric acid and its clinical correlation in children with dilated cardiomyopathy.

BackgroundDilated cardiomyopathy (DCM) is the most common type of childhood cardiomyopathy and uric acid (UA) is considered closely associated with cardiovascular disease. There are few reports about the relationship between serum UA level and DCM in children, and the present study aimed to analyze the changes and clinical correlation of the two.MethodsThe clinical data of 49 children under 16 years old and who were hospitalized with DCM, and 44 healthy children who underwent physical examination in the same period at Tianjin Children’s Hospital from June 2015 to November 2019 were analyzed retrospectively.ResultsThe 49 children in the case group included 17 males and 32 females, aged from 2 to 172 months. The case group were divided into New York Heart Association (NYHA) functional class I (n=2), class II (n=17), class III (n=11), and class IV (n=19). The 44 healthy children selected as the control group included 20 males and 24 females aged from 2 to 161 months. The serum UA level was detected, and an ultrasonic cardiogram was conducted in each child. The serum UA level, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and left atrial diameter (LAD) of the case group were higher than that of the control group, while the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower than that of the control group, and significant statistical differences were seen between the two groups (P<0.01). The serum UA level, LVEDD, LVESD, and LAD of NYHAIII–IV class patients were higher than that of the NYHAI–II class, but LVEF and LVFS were lower than that of the NYHA I–II class, and there were significant statistical differences between the two groups (P<0.01). Statistical correlations were seen between the serum UA level and NYHA functional class, LVEDD, LVESD, LAD, LVEF, and LVFS (rs=0.599, 0.567, 0.579, 0.475, −0.333, −0.341, respectively, P<0.05).ConclusionsElevated serum UA levels exist in children with DCM and correlate with NYHA functional class and ultrasonic values. Change in serum UA levels may be used as a biomarker reflecting the severity of DCM in children.

Effect of orlistat on serum uric acid level in adults: A systematic review and meta-analysis of randomised controlled trials.

Hyperuricemia increases the risk of gout and cardiovascular diseases. Obesity increases the risk of hyperuricemia while weight loss (>5kg) has been reported to decrease urate. The effects of orlistat on serum uric acid (SUA) are still controversial. The aim of this meta-analysis was to evaluate the influence of orlistat on SUA levels in adults. Relevant studies, published up to May 2020, were searched systematically through PubMed/Medline, Scopus and Google Scholar. All relevant randomised controlled clinical trials were included. Meta-analysis was performed using random-effect model. Subgroup analysis, sensitivity analysis and meta-regression were also carried out. Overall 7 trials (9 datasets) that enrolled 1786 subjects were included. Orlistat showed in a significant change in SUA level (Difference in means: -17.661 μmol, 95% CI: -31.615 to -3.707, P=.01). A low heterogeneity observed across the studies (I2 = 25.119%). After categorising studies on the basis of duration and sample size, the effect of orlistat on SUA was significant. The results of meta-regression were showed that significant relationships were not found between orlistat and SUA in the duration of intervention. We found a significant reduction in SUA following orlistat therapy in adults.

Sodium-Glucose Cotransporter-2 (SGLT-2) Attenuates Serum Uric Acid (SUA) Level in Patients with Type 2 Diabetes.

Background Hyperuricemia has a strong association with diabetes mellitus. Hyperuricemia can lead to cardiovascular and renal complications in patients with diabetes. The goal of this study was to compare the effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors dapagliflozin and empagliflozin on serum uric acid (SUA) levels in patients with type 2 diabetes against traditional oral antihyperglycemic drugs (OADs). Methods In this double-blind randomized controlled trial, 70 patients with type 2 diabetes and elevated SUA levels were assigned to two treatment groups. Patients in group A received SGLT-2 inhibitors tablet dapagliflozin 5 mg to 10 mg and empagliflozin 10 mg to 25 mg. Group B patients received OADs such as glimepiride, metformin, sitagliptin, gliclazide, and glibenclamide as monotherapy or combination therapy. The changes in SUA level were primary end points while changes in body weight and body mass index (BMI) from baseline to end point were secondary end points. Results After four weeks of treatment, we noted a significant reduction of mean SUA levels in the SGLT-2 inhibitor group from 7.5 ± 2.5 to 6.3 ± 0.8 mg/dl versus comparator group from 7.1 ± 1.8 to 6.8 ± 2.2 mg/dl (p = 0.001). Mean body weight was significantly reduced in the SGLT-2 group from 82 ± 10.4 to 78 ± 12.5 kg versus comparator group from 78 ± 13.2 to 79.2 ± 9.7 kg (p = 0.001). Similarly, the mean BMI of patients in the SGLT-2 group was significantly reduced from 25.7 ± 3.2 to 24.2 ± 3.2 kg/m2 versus comparator group from 27.5 ± 4.2 to 28 ± 3.6 kg/m2 (p = 0.002). Conclusion SGLT-2 inhibitors have a strong potential to decrease SUA levels in patients with type 2 diabetes.

The Complex Relationship Between Serum Uric Acid, Endothelial Function and Small Vessel Remodeling in Humans.

Aims: The relationship between serum uric acid (SUA) and microvascular remodeling in humans remains largely unexplored. We assessed whether SUA provides additional information on the severity of microvascular remodeling than that obtained from the European Heart Score (HS), the patterns of microvascular remodeling associated with changes in SUA levels and the mediation by endothelial function and nitric oxide (NO) availability on this relationship. Methods: A total of 162 patients included in the microvascular dataset of the Italian Society of Hypertension with available information on SUA, media-to-lumen (M/L) ratio, media cross-sectional area (MCSA), endothelial function, NO availability and HS were included in the analysis. The top tertile of M/L ratio and MCSA were used to define severe microvascular remodeling. Results: A U-shaped association was observed between SUA and both M/L ratio and MCSA. Adjustment for HS did not affect these associations. SUA was able to reclassify a significant number of subjects without, and with, severe M/L ratio and MCSA remodeling over the HS alone. The microvascular remodeling associated with SUA levels presented a predominant hypertrophic pattern. SUA was inversely associated with endothelial function and NO availability. Structural equation modeling analysis controlling for the HS suggested that the association of SUA with M/L ratio and MCSA was mediated through changes in endothelial function and NO availability. Conclusions: The addition of SUA to the HS improves the identification of subjects with greater microvascular remodeling. The relationship between SUA and microvascular remodeling is mediated by endothelial function and NO availability.

Associations between changes in serum uric acid and the risk of myocardial infarction

BackgroundThe role of serum uric acid (SUA) in development of myocardial infarction (MI) is controversial. The current study aimed to investigate the association between both baseline SUA and changes in SUA and the risk of MI. MethodsThe current study included 71,449 Chinese participants (mean age, 50.9 years) free of MI during the time of follow-up. Participants were divided into 4 categories according to the SUA levels between baseline and the second follow-up: stable low, elevated, reduced and stable high. Multivariate Cox proportion models were used to calculated hazard ratios (HRs) and their 95% confidence intervals (CIs) for MI. ResultsDuring a median follow-up of 8.96 years, 837 MI cases were identified. After adjustment for potential confounders, MI risk was only associated with stable high SUA, the HR was 1.42 (95%CI: 1.02–1.92, p = 0.03), compared with those with stable low SUA. However, there was no association between hyperuricemia at baseline and MI, the HR was 1.14 (95%CI: 0.91–1.42, p = 0.19) compared with those with normal SUA. Subgroup analyses stratified by age, sex, hypertension, diabetes and estimated glomerular filtration rate were also confirmed no significant difference (p-interaction >0.05 for all). Furthermore, mediation analyses revealed 14.14% of association was mediated by hypertension. ConclusionsOnly stable high SUA was associated with increased higher risk of MI. Changes in SUA levels in any other direction or high SUA levels at baseline were not associated with risk of MI.

P5413Effect of empagliflozin as add-on therapy on serum uric acid level in patients with type 2 diabetes hospitalized for acute decompensated heart failure: a prospective randomized controlled study

Abstract Background Elevated serum uric acid (UA) level has been shown to be associated with reduced survival among patients (pts) with heart failure. Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower serum uric acid level in pts with type 2 diabetes mellitus (T2D). Empagliflozin, one of the SGLT2 inhibitors, has been shown to reduce the risk of cardiovascular mortality in T2D pts with cardiovascular disease, and involvement of UA lowering effect by empagliflozin in the reduction of cardiovascular mortality has been suggested. However, little is known about the effect of empagliflozin as add-on therapy on serum UA level in T2D pts with acute decompensated heart failure (ADHF). Purpose We sought to elucidate the effect of empagliflozin as add-on therapy on serum UA level in T2D pts with ADHF. Methods We enrolled 38 consecutive T2D pts admitted for ADHF. On admission, enrolled pts were randomly assigned in a 1:1 ratio to either empagliflozin add-on therapy (EMPA(+)) or conventional glucose-lowering therapy (EMPA(−)). All pts in EMPA(+) group received empagliflozin (10 mg/day) throughout the study period. Left ventricular ejection fraction (LVEF) was measured at baseline using echocardiography. Body weight and vital signs, such as blood pressure and heart rate, were measured, and blood and urine samples were collected at baseline and 1, 2, 3 and 7 days after randomization. Renal handling of UA was evaluated by fractional excretion of UA (FEUA). Results Twenty pts were assigned to the EMPA(+) group, and 18 pts were assigned to the EMPA(−) group. There were no significant baseline differences in LVEF, plasma brain natriuretic peptide level, body mass index, or serum creatinine level between the EMPA(+) and EMPA(−) groups. In addition, prevalence rate of hyperuricemia, serum UA level, and FEUA did not significantly differ between the two groups at baseline. However, there was significant difference in the change in serum UA level from baseline at 2, 3 and 7 days after randomization between the two groups (Figure A). As a result, serum UA level was significantly lower in the EMPA(+) group than in the EMPA(−) group at 7 days after randomization (6.2±1.8 mg/dL vs 7.8±1.8 mg/dL, p=0.0127). Moreover, FEUN of the EMPA(+) group was significantly higher at 1, 2 and 7 days after randomization (Figure B), which suggested that serum UA level was lowered in the EMPA(+) group by increased urinary excretion of UA. Figure 1 Conclusions This study demonstrated that empagliflozin as add-on therapy can lower serum UA level in T2D pts with ADHF through the effect on the urinary excretion rate of UA.

Longitudinal association between serum uric acid levels and multiterritorial atherosclerosis.

Multiterritorial atherosclerosis has dramatically increased annual risk of adverse cardiovascular events than atherosclerotic disease with single‐artery affected. Serum uric acid (SUA) is an important predictor of stroke and atherosclerosis; however, which is supported by few direct evidence based on cohort studies. A prospective cohort study including 2644 North Chinese adults aged ≥40 years was performed in 2010‐2012 to investigate the association between SUA and multiterritorial vascular stenosis. Hyperuricaemia was defined as SUA levels >6 and >7 mg/dL for males and females, respectively. All participants underwent twice transcranial Doppler (TCD) and bilateral carotid duplex ultrasound to evaluate intracranial artery stenosis (ICAS) and extracranial arterial stenosis (ECAS) and peripheral arterial disease (PAD) was determined by ankle‐brachial index (ABI) on January 2010 and January 2012 based on regular health check‐ups. The cumulative incidence of vascular stenosis was significantly higher in subjects with hyperuricaemia than in those without hyperuricaemia (54.1% vs. 34.7%, P < 0.001). The adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for new on‐set vascular stenosis due to hyperuricaemia and a 1‐mg/dL change in SUA level were 1.75 (1.32‐2.31) and 1.29 (1.21‐1.38), respectively. Furthermore, in the gender‐stratified analysis, the association between SUA levels and ICAS was statistically significant in males (OR: 2.02; 95% CI: 1.18‐3.46), but not females (OR: 0.85, 95% CI: 0.41‐1.76, P for interaction: 0.026).

The Protective Effects of Increasing Serum Uric Acid Level on Development of Metabolic Syndrome

BackgroundIt has not been determined whether changes in serum uric acid (SUA) level are associated with incident metabolic syndrome (MetS). The aim of the current study was to investigate the relationship between changes in SUA level and development of MetS in a large number of subjects.MethodsIn total, 13,057 subjects participating in a medical health check-up program without a diagnosis of MetS at baseline were enrolled. Cox proportional hazards models were used to test the independent association of percent changes in SUA level with development of MetS.ResultsAfter adjustment for age, systolic blood pressure, body mass index, fat-free mass (%), estimated glomerular filtration rate, smoking status, fasting glucose, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and baseline SUA levels, the hazard ratios (HRs) (95% confidence intervals [CIs]) for incident MetS in the second, third, and fourth quartiles compared to the first quartile of percent change in SUA level were 1.055 (0.936 to 1.190), 0.927 (0.818 to 1.050), and 0.807 (0.707 to 0.922) in male (P for trend <0.001) and 1.000 (0.843 to 1.186), 0.744 (0.615 to 0.900), and 0.684 (0.557 to 0.840) in female (P for trend <0.001), respectively. As a continuous variable in the fully-adjusted model, each one-standard deviation increase in percent change in SUA level was associated with an HR (95% CI) for incident MetS of 0.944 (0.906 to 0.982) in male (P=0.005) and 0.851 (0.801 to 0.905) in female (P<0.001).ConclusionThe current study demonstrated that increasing SUA level independently protected against the development of MetS, suggesting a possible role of SUA as an antioxidant in the pathogenesis of incident MetS.

Effects of dapagliflozin on serum uric acid levels in hospitalized type 2 diabetic patients with inadequate glycemic control: a randomized controlled trial.

BackgroundRaised serum uric acid (SUA) level is commonly observed in patients with type 2 diabetes mellitus (T2DM) and is associated with increased morbidity and mortality. Sodium-glucose cotransporter 2 inhibitor, a novel oral diabetic drug, might exert a potential hypouricemic effect. We evaluated the effects of dapagliflozin on SUA levels in hospitalized T2DM patients with inadequate glycemic control.MethodsIn this randomized controlled trial, 59 T2DM hospitalized patients with inadequate glycemic control were assigned to the dapagliflozin 10 mg group (n=29) or the control group (n=30). The primary outcome was changes in SUA levels from the baseline to good glycemic control. Additional outcomes included correlations between baseline SUA levels, urinary parameters, and the changes in SUA levels. This trial is registered in the Chinese Clinical Trial Registry (number ChiCTR1800015830).ResultsCompared to baseline level, SUA levels had significantly decreased in both groups (P<0.001 for the dapagliflozin group and P=0.013 for the control group). Mean changes from baseline in SUA levels for dapagliflozin vs the control group were 68.03 vs 25.90 μmol/L (P=0.0406). Adjusted mean SUA levels were lower in the dapagliflozin group (273.28 vs 307.57 μmol/L; P=0.0089). In T2DM patients treated with dapagliflozin, the decrease in SUA levels was positively correlated with baseline SUA levels (P<0.0001) but not correlated with changes in 24-hour urine volume, 24-hour urine glucose, or 24-hour urinary uric acid.ConclusionDapagliflozin could improve glycemic control and lower SUA levels in hospitalized patients with uncontrolled T2DM. Longer-time trials are required to further demonstrate the hypouricemic effect of dapagliflozin and explore the potential underlying mechanisms.

Effects of a Dietary Approach to Stop Hypertension (DASH) Diet Intervention on Serum Uric Acid in African Americans With Hypertension.

To examine whether partial replacement of a diet typical of the average American diet with Dietary Approaches to Stop Hypertension (DASH)-related foods in the home environment lowers the serum uric acid (UA) level in individuals with hypertension. We conducted an ancillary study of a randomized trial of African American adults with controlled hypertension from an urban clinic. Participants were assigned to either a control group or an intervention (DASH-Plus) group. DASH-Plus participants received coach-directed dietary advice, assistance with purchasing DASH-related foods ($30/week), and home delivery of food via a community supermarket. Participants in the control group received a DASH diet brochure and a debit card account ($30/week) to purchase foods. Serum UA levels were measured at baseline and after 8 weeks. Of the original 123 randomized participants, 117 had available serum UA measurements. Seventy percent of the participants were women, the mean ± SD age was 59 ± 9.5 years, and the mean ± SD serum UA level was 6.4 ± 1.7 mg/dl. The DASH-Plus diet did not reduce serum UA levels compared with the control diet (difference in difference -0.01 mg/dl [95% confidence interval -0.39, 0.38]). However, there was a significant trend toward a greater reduction in the serum UA level in participants with higher baseline serum UA levels (P for trend = 0.008). Baseline changes in the serum UA level were inversely associated with changes in systolic blood pressure (P = 0.002), diastolic blood pressure (P = 0.001), and urinary sodium excretion (P = 0.05). Overall, in African American individuals, partial replacement of a typical diet with DASH foods did not lower serum UA levels compared with a control diet. However, there was a significant trend toward a greater reduction in serum UA levels in subjects with higher baseline serum UA levels. Furthermore, changes in serum UA levels were associated with known correlates, suggesting heterogeneity of effects in the treatment and control arms. Future pragmatic studies of consumption of the DASH diet to lower serum UA levels should optimize replacement strategies and enroll individuals with hyperuricemia or gout.

Hypouricaemic effects of yoghurt containing Lactobacillus gasseri PA-3 in patients with hyperuricaemia and/or gout: A randomised, double-blind, placebo-controlled study

Purpose: Lactobacillus gasseri PA-3 (PA-3) has been previously shown to decrease serum uric acid (SUA) levels in subjects with increased SUA. In this study, we investigated whether PA-3 is also capable of decreasing SUA levels in patients with hyperuricaemia and/or gout.Methods: Twenty-five patients with hyperuricaemia and/or gout completed this study. Urate-lowering drugs were discontinued for 12 weeks (week −4 to week 8). After flushing of urate-lowering drugs for 4 weeks (week 0), patients were randomised equally to receive diets containing yoghurt beverages with PA-3 or without PA-3 for a duration of 8 weeks (week 8). The intention to treat (ITT) population included all subjects who were randomised, and the per-protocol (PP) population included subjects who completed the experiment with compliance. We evaluated SUA levels at the end of the study as well as changes in SUA levels in comparison to week 0.Results: In both ITT and PP analyses, there were no significant differences in SUA levels or in the changes in SUA levels compared to week 0 between the two groups. However, in a sub-population whose SUA levels at week 0 were within one SD of the mean of the whole PP population, changes in SUA levels in the group consuming PA-3-containing yoghurt were significantly lower than those of the control group (p = .0378).Conclusion: PA-3-containing yoghurt improves SUA levels, even in patients with hyperuricaemia and/or gout.