High Uric Acid Research Articles

A Population Based Study of Liver Function amongst Adults with Hyperuricemia and Gout in the United States.

To examine the association between uric acid levels and liver enzyme functions amongst adults with hyperuricemia and gout in the United States. The National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2016 was used to study the research objective. Data were analyzed for descriptive statistics and for differences using the t test, Chi-square test and ANOVA. A regression analysis was performed to determine association between demographics and liver enzymes. A p value of <0.05 or <0.001 was considered statistically significant. A total of 14,946 adults (≥20 yrs.) were included in this study. Sample mean age was 49 ± 0.15 yrs., and 54% were female. Overall, 15% adults had elevated uric acid levels (≥6.8 mg/dL), men had significantly higher uric acid levels than women (6 mg/dL vs. 4.8 mg/dL). High uric acid levels were associated with more than two times higher odds of elevated ALT, AST and GGT (p < 0.001). Similarly, gender-based target uric acid values were associated with two-fold increased odds of GGT, over one-and-a-half fold higher odds of ALT and AST (p < 0.001). Regression analysis showed significant association between age, gender, race/ethnicity, body mass index, and hypertension and ALT, AST, ALP, total bilirubin and GGT (p < 0.001). Adults with hyperuricemia and gout are most likely to develop liver dysfunctions and suffer associated morbidities. Such patients need to be appropriately monitored and managed for their liver functions and to prevent associated morbidities.

Hyperuricemia in patients with pulmonary hypertension: A study in a tertiary care center

Pulmonary Hypertension is one of a life-threatening disease with high rate of patient mortality. Decreased cardiac output and tissue hypoxia is measured using Uric acid as a marker for assessment of pulmonary hypertension. 75 patients who were diagnosed with a mean pulmonary arterial pressure of &amp;#62;22mmHg were categorized as group A and 75 healthy patients were considered to be Group B. Blood was collected for Uric acid, creatinine and total Bilirubin estimation. Pulmonary arterial systolic pressure as well as the ventricular function of the patients was evaluated using Colour Doppler ECG and a value of ≥50 mmHg, or a mean pulmonary arterial pressure (at rest) of ≥25 mmHg was taken and the right arterial pressure was calculated. Using the Simpson’s formula, the right and left ventricular ejaculation factors (RVEF, LVEF) were calculated. The serum uric acid levels among the patients were 8.3±1.4mg/dL, creatinine levels were 2.1 ± 0.5 mg/dL, and the total bilirubin levels were 1.9 ± 0.8 mg/dL all of which was significantly higher than the controls. The uric acid levels were also positively correlated to the NHYA class. The blood pressure and the pulmonary arterial pressure were also higher than that of the controls. The correlation was done between the elevated uric acid and ejection fractions and the correlation coefficients of MPAP, LVEF, RVEF and the NYHA class were all significantly associated and the values were 0.394, -0.513, -0.467 and 0.38 respectively. High serum uric acid levels is significantly associated with higher blood pressure, pulmonary arterial pressure and NYHA class. High serum uric acid levels can be a reliable prognostic marker for the detection of pulmonary hypertension. Early therapy may help in the reduction of mortality rate.

High Serum Uric Acid and High-Sensitivity C Reactive Protein Concentrations Predict Three-Year Cardiovascular Mortality in Patients Treated With Continuous Ambulatory Peritoneal Dialysis.

Aims: This study aims to access the predicting value of serum uric acid (UA) and high-sensitivity C reactive protein (hs-CRP) concentration on three-year cardiovascular-related mortality in patients performing continuous ambulatory peritoneal dialysis (CAPD).Methods: A total of267 CAPD patients [150 male (56.2%); mean age 48.93 ± 13.58 years] were included in our study. All patients had measured serum UA and hs-CRP concentration. A high-sensitivity particle-enhanced immunoturbidimetric assay determined serum hs-CRP; serum UA levels were determined using an enzymatic colorimetric assay. All patients were followed for three years to detect cardiovascular-related mortality by cardiologists and stroke specialists.Results: Mean serum UA level was 415.16 ± 84.28 µmol/L, 58.4% of patients had increased serum UA level. Median serum hs-CRP level was 2 (1-4) mg/L, 12.4% of patients had increased serum hs-CRP level. During 36 months of follow-up, 41 patients (15.4%) had cardiovascular-related mortality. The results of Cox proportional hazards regression showed that hypertension, diabetes, high serum UA and hs-CRP were risk factors that related to cardiovascular-related mortality (p<0.05). The receiver operating characteristic (ROC) curve and Kaplan-Meier analysis results showed that UA and hs-CRP level had predictive value for three-year cardiovascular-related mortality in CAPD patients [uric acid: area under the curve (AUC)=0.822; hs-CRP: AUC=0.834, p < 0.001].Conclusion: High serum UA and hs-CRP levels were predictive factors of cardiovascular-related mortality in CAPD patients.

Hyperuricemia is a risk factor for the progression to end-stage renal disease in minimal change disease.

BackgroundMinimal change disease (MCD) is one of the most common causes of nephrotic syndrome worldwide. Hyperuricemia increases the end-stage renal disease (ESRD) risk in glomerulonephritis. In this study, we aimed to determine the effect of high serum uric acid levels on the progression to ESRD in MCD.MethodsA total of 800 patients diagnosed with MCD by kidney biopsy were retrospectively analyzed. We determined the relationship of hyperuricemia with the progression to ESRD in MCD using the Cox proportional hazard model and Kaplan-Meier survival analysis. The primary outcome was defined as the initiation of dialysis or kidney transplantation.ResultsA total of 42 patients (5.3%) progressed to ESRD during the follow-up period. In the restricted cubic spline curve, serum uric acid levels exhibited a positive correlation with ESRD progression in patients with MCD. In the fully adjusted model, the risk of MCD progression increased by 29% for every 1 mg/dL increase in the baseline serum uric acid level (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.09–1.54; p = 0.004). Falling into the high uric acid group (serum uric acid level > 7 mg/dL in men and > 6 mg/dL in women) was also a risk factor for progression of MCD to ESRD (HR, 3.40; 95% CI, 1.59–7.31; p < 0.001).ConclusionOur study shows that hyperuricemia is an independent risk factor for the progression to ESRD in patients with MCD.

The Relationship between Serum Uric Acid and Ejection Fraction of the Left Ventricle

Study basis: As a byproduct of protein metabolism, serum uric acid is a controversial risk factor and is the focus of several recent studies in the field of cardiovascular disease. Whether serum uric acid is involved in the development of these pathologies alone or in conjunction with other factors is a matter of debate. Objective: The objective of this study is to assess the direct relationship between serum uric acid and the ejection fraction. Methods: A retrospective study of 303 patients with heart failure, classified according to the ESC guidelines, was conducted, and several parameters, along with the relationship between serum uric acid and ejection fraction, were characterized. Results: A direct relationship between the level of serum uric acid and the ejection fraction was established (p = 0.03); patients with higher uric acid had an increased risk of having a lower ejection fraction. Conclusions: Serum uric acid, even when asymptomatic, is linked with the level of the ejection fraction of the left ventricle.

Endogenous fructose is correlated with urinary albumin creatinine ratios and uric acid in type 2 diabetes mellitus

AimTo detect the expression levels of fasting serum fructose and ketohexokinase (KHK) in patients with type 2 diabetes mellitus (T2DM) at different stages of urinary albumin creatinine ratios (UACR) and serum uric acid (sUA). Methods339 T2DM patients and 107 normal volunteers were divided into the normal uric acid (275 cases) and high uric acid group (171 cases) according to uric acid levels. T2DM patients were divided into the normal albuminuria group (118 cases, UACR < 30 mg/g), microalbuminuria group (112 cases, UACR 30–300 mg/g) and large amount of albuminuria group (109 cases, UACR > 300 mg/g). Levels of fasting serum fructose and KHK were detected and statistical analysis was carried out. ResultsFasting serum fructose and KHK levels increased with the increase of UACR and sUA (P < 0.05). Correlation analysis showed that fasting serum fructose and KHK levels were positively correlated with UACR and sUA (P < 0.05). Ridge regression analysis showed that fasting serum fructose and KHK were also correlated with urinary albumin and uric acid (P < 0.05). ConclusionFasting serum fructose and KHK in endogenous fructose are associated with serum uric acid and urinary albumin levels in patients with T2DM.Trial number: ChiCTR2000039870.

300Association between rs2231142 of ABCG2 and gout, hyperuricemia and uric acid: Systematic review and meta-analysis

Abstract Background Genome-wide association studies showed that rs2231142 (C421A) of ABCG2 gene has strong effects on gout and uric acid (UA). However, replication studies showed conflicting results. We aimed to pool effects of rs2231142 on gout, hyperuricemia, and UA across studies. Methods Studies were located from MEDLINE and Scopus until 17th June 2018. Data extractions were performed by two independent reviewers. Hardy-Weinberg equilibrium was checked. Genotype effects were pooled by ethnicity using mixed-effect logistic model for gout and hyperuricemia and multivariate meta-analysis for UA. Publication bias was assessed using funnel plots and Egger’s tests. Results Thirty studies were eligible; 21, 5, and 8 studies assessed association between rs2231142 and gout, hyperuricemia, and UA, respectively. Carrying AA and CA genotypes were 3.2 (2.4, 4.4) and 1.6 (1.5, 1.8) higher odds to develop gout in Caucasians. Likewise, in Asians, the ORs for corresponding genotypes were 4.5 (4.1, 5.0) and 2.1 (2.0, 2.3) for gout; 2.3 (1.8, 2.8) and 1.6 (1.4, 1.8) for hyperuricemia. Mean differences of UA in Caucasians carrying AA and CA were 50.4 (32.7, 68.2) and 19.5 (14.2, 24.7) µmol/l compared with those carrying CC genotype while in Asians, they were 18.4 (8.7, 28.1) and 11.5 (4.1, 18.9) µmol/l, respectively. Additive gene effects were suggested. Conclusions Significant effects of rs2231142 on gout, hyperuricemia, and elevated UA were confirmed. Our findings should be useful in personalized risk scores for prediction of gout and diseases related to high UA. Key messages rs2231142 increased the risk of gout and UA in Asians and Caucasians

Retraction Statement.

Retraction Statement.

Serum Uric Acid Level in Oral Cancer Patients -Original Study

Background Uric acid is a result of the metabolic breakdown of purine digestion. Serum uricacid ensures against carcinogenesis by means of its cell reinforcement properties and forestalls thedevelopment of oxygen extremists. High blood groupings of uric acid can prompt gout and are relatedwith diabetes and development of kidney stones. Serum uric acid fixation mirror the harmony betweenuric acid combination and discharge. Studies have indicated that high uric acid is a danger factorfor hypertension, diabetes and Cardio Vascular illness.Squamous cell carcinoma is characterized asthreatening epithelial neoplasm showing squamous separation as described by the development of keratinor the bury cell spans. It also includestheinitialpresenceofaprecancerous lesion.Moreover,specificmedicalconditionscancontributetotheoral potentially malignant disordersprevalenceOral squamous cellcarcinoma is the most well-known neoplasm speaking to over 80% of all oral malignancy cases. Serum uricacid has been proposed to be related with the danger of malignant growth and it was seen that raised degreesof serum uric acid was related with an expanded disease frequency contrasted with typical qualities.Aim and Objectives : The aim of this study is to evaluate the serum uric acid level in oral cancer patients,to find out the association between low serum uric acid level and risk of squamous cell carcinoma and tocompare the serum uric acid levels in oral cancer patients with normal individuals.Materials and Methods : This is a hospital based study to find out the uric acid level in oral cancer patients.The participants were selected from the out patients, Department of Oral Pathology and Microbiology. Thestudy included a total numbe of 28 persons. Out of the 28 persons 15 oral cancer patients were selected forthe experimental group. The remaining 13 subjects were in the normal group.Results : In this study, mean uric acid level in this stroke population with CAD is 6.37 mgs/dl and in thosewithout CAD is 5.00 mgs/dl and thus establishes a statistically significant relationship (‘p’0.0004). Whenmales and females are considered, males have a significant association with a ‘p’ value of 0.0003. The buccalmucosa of the oral cavity was the most common involved site followed by the vestibule.Conclusion : The studies showed that serum uric acid level was significantly lower in oral cancer patientscompared to the control group. Uric acid may prevent the formation of oxygen radicals and there by protectagainst carcinogenesis. In human’s uric acid is the most abundant antioxidant and is an important intracellular free radical scavenger. Early detection of oral cancer and Habit should be controlled to reducemortality rates and help to provide successful cancer treatment.

Hyperuricemia, Elevated Body Mass Index, Female Sex, and Albuminuria Increase the Probability of Elevated High-Sensitivity C-Reactive Protein: Results From the National Health and Nutrition Examination Survey 2015-2018.

Importance: High uric acid (UA) is hypothesized to worsen kidney and cardiovascular disease morbidity via activation of systemic inflammation. Clinical trials of UA modification report reduction of the inflammatory marker high sensitivity C-reactive protein (hs-CRP) as an outcome measure, but studies have not demonstrated that hyperuricemia independently increases hs-CRP when adjusted for important confounders such as body mass index (BMI), sex, and age.Objective: To identify clinical risk factors for elevated hs-CRP, including but not limited to hyperuricemia, through a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) 2015–2018.Results: In the final multivariate logistic regression model, the exposure with the strongest effect on the odds of elevated hs-CRP was BMI in the fourth quartile, OR = 13.1 (95% CI 6.25–27.42), followed by female sex (OR = 4.9, 95% CI 2.92–8.34), hyperuricemia (OR = 2.2, 95% CI 1.36–3.45), urine albumin creatinine ratio (ACR; OR = 1.5, 95% CI 1.09–2.18), poor overall health (OR = 1.4, 95% CI 1.18–1.58), and interactions between hyperuricemia and sex (OR = 1.4, 95% CI 1.05–1.83), and between BMI and sex (OR = 1.2, 95% CI 1.03–1.47). Notably, chronic kidney disease (CKD) and CKD surrogates were not associated with hs-CRP despite urine ACR maintaining a significant independent effect.Conclusions: In this national population-based study, we demonstrated that hyperuricemia significantly increases the odds of elevated hs-CRP, independent from BMI, female sex, urine ACR, and overall health status. Further study is recommended to better understand the sex difference in this association and the role of albuminuria, but not CKD, in systemic inflammation.

Comparative analysis of clinical and imaging data between patients with myelin oligodendrocyte glycoprotein antibody disease and patients with aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder

We aimed to compare the clinical data, laboratory findings, and imaging characteristics of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and aquaporin 4 antibody (AQP4)-positive neuromyelitis optica spectrum disorder (NMOSD), as detailed comparative analyses of laboratory data for both diseases are rare. Our retrospective study compared the clinical data, laboratory findings, and imaging characteristics of 118 AQP4-positive patients with first-episode NMOSD and 25 patients with first-episode MOGAD. Logistic regression was used to determine the factors that differentiated MOGAD and AQP4-positive NMOSD. There were significant differences in age, symptoms, recurrence rate, laboratory indicators, and imaging examinations between patients with MOGAD and patients with AQP4-positive NMOSD. Patients with MOGAD were younger and had higher levels of uric acid than those with AQP4-positive NMOSD. The proportion of cortical gray matter/juxtacortical white matter lesions was significantly higher in the MOGAD group than in the NMOSD group. Logistic regression revealed that young age [odds ratio (OR) = 0.947, 95% confidence interval (CI) = 0.905-0.99], high uric acid level (OR = 1.016, 95% CI = 1.006-1.027), and cortical gray matter/juxtacortical white matter involvement (OR = 3.889, 95% CI = 1.048-14.442) were significantly related to MOGAD. The multivariate analysis of the present study demonstrated that age, uric acid level, and the presence of lesions in the cortical gray matter/juxtacortical white matter can aid in distinguishing patients with AQP4-positive NMOSD from those with MOGAD. These factors may also aid in determining which patients should be tested for antibodies.

Prevalence of hyperuricemia in cerebrovascular accidents and its correlation with their outcome

Introduction: Cerebrovascular accident or stroke is a disease of the vascular system of the brain.According to ICD 11, stroke is classified as a neurological disease and not under the circulatorysystem. It is the second leading cause of death worldwide. It cannot be said that high Serum UricAcid [SUA] amongst patients with cerebrovascular accidents is directly correlated with theiroutcome. The present study planned to estimate uric acid levels and their association in acute strokepatients, both ischemic and hemorrhagic. Method: A total of 100 stroke patients admitted under theneurology department were included in the study. Brain imaging (CT/MRI) was performed. Theserum uric acid was estimated. Results: Out of a total of 100 patients, 74 were males, and 26 werefemales. Nine patients were less than 45 years old and 91 patients were 45 and above. Thirty-ninepatients had ischemic, and 61 patients had a hemorrhagic stroke, respectively. Out of 100 patients,23 patients had normal uric acid levels (&lt;7mg/dl). Seventy-seven patients were with high uric acidlevels. The mean serum uric acid concentration in male patients was 8.48±2.7and 9.20±2.7 infemales. Among the total 100 cases, 69 survived, and the remaining 31 were among the non-survivor group at the time of discharge. Mean serum uric acid in stroke survivors was 8.5±2.6mg/dl, while in non-survivors, it was 8.6±2.2 mg/dl. There was no significant difference between thelevels of uric acid among survivors and non-survivors. Conclusions: The prevalence ofhyperuricemia (&gt;9mg/dl) amongst stroke patients was 77% in the present study. The values ofserum uric acid were significantly elevated in the patients aged &gt; 45 years. The serum uric acidvalues were high among the group of hyperglycemic and hypertensive patients at the time ofadmission. There was no significant difference between the levels of uric acid among survivors andnon-survivors.

Evaluation of predictors of severe-moderate COVID-19 infections at children: A review of 292 children.

Although the underlying disease is associated with a severe course in adults and laboratory abnormalities have been widely reported, there are not sufficient data on the clinical course of coronavirus disease 2019 (COVID‐19) in children with pre‐existing comorbid conditions and on laboratory findings. We aimed to describe the independent risk factors for estimating the severity of the COVID‐19 in children. All children between 1 month and 18 years old who were hospitalized during the period of March 11–December 31, 2020, resulting from COVID‐19 were included in the study. Patients were categorized into mild (group 1) and moderate + severe/critically (group 2) severity based on the criteria. Demographic characteristics, comorbidities, and laboratory variables between the two groups were compared. A total of 292 children confirmed to have COVID‐19 infection were included in the study. The most common associated diseases were obesity (5.1%) and asthma bronchiale (4.1%). We observed that disease progressed more severely in patients with underlying diseases, especially obesity and asthma bronchiale (for patients with obesity odds ratio [OR] 9.1, 95% confidence interval [CI] 1.92–43.28, p = 0.005 and for patients with asthma bronchiale OR 4.1, 95% CI 1.04–16.80, p = 0.044). In group 2 patients, presence of lymphopenia and hypoalbuminemia, and also an elevation in serum levels of C‐reactive protein, procalcitonin, and uric acid were detected and these results were statistically significant (p values; p < 0.001, p = 0.046, p = 0.006, p = 0.045, p < 0.001, respectively). The strongest predictor of moderate‐severe COVID‐19 infections in the children was uric acid, with an odds ratio of 1.6 (95% CI 1.14–2.13, p = 0.005) and lymphocytes with an odds ratio of 0.7 (95% CI 0.55–0.88, p = 0.003). Although children are less susceptible to COVID‐19, the pre‐existing comorbid condition can predispose to severe disease. In addition, lymphopenia and high uric acid are indicators that COVID‐19 infection may progress more severely.

Mesenchymal stem cells transplantation attenuates hyperuricemic nephropathy in rats

Mesenchymal stem cells (MSCs), due to their multi-directional differentiation, paracrine and immunomodulation potentials, and the capacity of homing to target organ, have been reported to facilitate regeneration and repair of kidney and improve kidney function in acute or chronic kidney injury. The present study was aimed to evaluate whether MSCs could have a protective effect in hyperuricemic nephropathy (HN) and the underlying mechanisms. A rat HN model was established by oral administration of a mixture of potassium oxonate (PO, 1.5 g/kg) and adenine (Ad, 50 mg/kg) daily for 4 weeks. For MSCs treatment, MSCs (3 × 106 cells/kg per week) were injected via tail vein from the 2nd week for 3 times. The results showed that along with the elevated uric acid (UA) in HN rats, creatinine (CREA), blood urea nitrogen (BUN), microalbuminuria (MAU) and 24-hour urinary protein levels were significantly increased comparing with the normal control rats, while decreased after MSCs treatment. Moreover, the mRNA levels of inflammation and fibrosis-related gene were reduced in UA + MSCs group. Consistently, hematoxylin-eosin (HE) staining results showed the destruction of kidney structure and fibrosis were significantly alleviated after MSCs administration. Similarly, in vitro, NRK-52Es cells were treated with high concentration UA (10 mg/dL) in the presence of MSCs, and we found that MSCs co-culture could inhibited UA-induced cell injury, characterized as improvement of cell viability and proliferation, inhibition of apoptosis, inflammation, and fibrosis. Collectively, MSCs treatment could effectively attenuate UA-induced renal injury, and thus it might be a potential therapy to hyperuricemia-related renal diseases.

High Uric Acid Level Predicts Early Neurological Deterioration in Intracerebral Hemorrhage.

ObjectiveIncreased level of serum uric acid (UA) is often considered a risk factor for ischemic stroke. However, there are limited data on the association between UA and intracerebral hemorrhage (ICH). This study aimed to examine the connection between UA and early neurological deterioration (END) in patients with ICH.MethodsThis is a prospective observational study. Patients with ICH were enrolled from January 2017 to December 2020. END was diagnosed as the Canadian Stroke Scale (CSS) score decreased ≥1 points between admission and 48 hours. UA was measured at admission. Multivariable logistic regression analysis was performed to explore the relationship between serum UA and END.ResultsOf the 498 enrolled patients, 132 (26.5%) were developed with END. Patients with END had a significantly higher level of serum UA (332 vs 270 µmol/L, P < 0.001). Univariate logistic regression analysis indicated that patients with the highest quartile of UA level had an OR of 3.256 (95% CI: 1.849–5.734, P < 0.001) for END compared with those with the lowest quartile of UA level. After adjusting for major confounders, the highest UA quartile remained as an independent predictor for END (OR = 2.282, 95% CI: 1.112–4.685, P = 0.013).ConclusionHigher serum UA level was independently associated with END in patients with ICH; therefore, intervention to lower UA level may be worth considering.

High uric acid levels in overweight and obese children and their relationship with cardiometabolic risk factors: what is missing in this puzzle?

The prevalence of hyperuricemia, a common disorder, has been increasing. Moreover, the association between obesity, serum uric acid levels, and cardiometabolic markers in children is unclear. Therefore, this study aimed to analyze the inter-relationships between these factors in a sample of children aged 6-12years. We evaluated 764 children and stratified them according to their body mass index (BMI). Blood pressure and uric acid, creatinine, lipid, and glycemic profiles were evaluated, and the estimated glomerular filtration rate (eGFR) and the homeostatic model assessment for insulin resistance (HOMA-IR) index were calculated. There was a significant linear trend of increasing systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), total cholesterol, low-density lipoprotein cholesterol (LDLc), uric acid, insulin levels, and HOMA-IR index values corresponding with overweight and obese groups; however, high-density lipoprotein cholesterol (HDLc) levels decreased with increasing obesity. Themean creatinine level and eGFR were similar across all BMI groups. Uric acid levels were significantly correlated withBMI (r=0.527), waist circumference (r=0.580), SBP (r=0.497), DBP (r=0.362), TG (r=0.534), total cholesterol (r=0.416), LDLc (r=0.286), HDLc (r=-0.248), insulin (r=0.613), and HOMA-IR index (r=0.607). Multiple regression analyses showed that BMI (B=0.071; SE=0.012; p<0.001), TG (B=0.004; SE=0.001; p<0.001), LDLc (B=0.003; SE=0.001; p=0.006), and insulin (B=0.066; SE=0.007; p<0.001) (R2=0.460) were significant predictors of increased uric acid levels and explained 46% of the variability in uric acid in these children. Our findings suggest that overweight or obese children are more likely to have higher uric acid levels. Moreover, several cardiometabolic risk factors were strongly associated with high uric acid levels.

Hyperuricemia-induced endothelial insulin resistance: the nitric oxide connection.

Hyperuricemia, defined as elevated serum concentrations of uric acid (UA) above 416µmol L-1, is related to the development of cardiometabolic disorders, probably via induction of endothelial dysfunction. Hyperuricemia causes endothelial dysfunction via induction of cell apoptosis, oxidative stress, and inflammation; however, it's interfering with insulin signaling and decreased endothelial nitric oxide (NO) availability, resulting in the development of endothelial insulin resistance, which seems to be a major underlying mechanism for hyperuricemia-induced endothelial dysfunction. Here, we elaborate on how hyperuricemia induces endothelial insulin resistance through the disruption of insulin-stimulated endothelial NO synthesis. High UA concentrations decrease insulin-induced NO synthesis within the endothelial cells by interfering with insulin signaling at either the receptor or post-receptor levels (i.e., proximal and distal steps). At the proximal post-receptor level, UA impairs the function of the insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) in the insulin signaling pathway. At the distal level, high UA concentrations impair endothelial NO synthase (eNOS)-NO system by decreasing eNOS expression and activity as well as by direct inactivation of NO. Clinically, UA-induced endothelial insulin resistance is translated into impaired endothelial function, impaired NO-dependent vasodilation, and the development of systemic insulin resistance. UA-lowering drugs may improve endothelial function in subjects with hyperuricemia.

Clinical features in pulmonary tuberculosis patients combined with diabetes mellitus in China: An observational study.

BackgroundConsideration of the huge burden both of tuberculosis (TB) and diabetes mellitus (DM) in China as a major public health issue, research focused on the relationship between DM and TB was needed.MethodsAn observational study was conducted (2015‐2018) in regional representative TB and lung disease hospitals in China. All the adult patients newly diagnosed of pulmonary TB were consecutively recruited in this study.ResultsA total of 1417 patients newly diagnosed pulmonary TB was recruited in this research, 312 (22.02%) of them had the history of type 2 DM. Majority of patients were with fatigue, loss of weight and mild anaemia in TB‐DM group compared with TB‐NDM group (58.3% vs 47.5%, p = .001; 8.21 ± 6.2 vs 5.74 ± 4.0 kg, p < .001, 88.9% vs 77.6% p = .021). TB‐DM patients were with higher the proportion of TB severity score ≥3, compared with TB‐NDM patients, but the distributions of drug susceptibility testing (DST) analysis were not significantly different between the two groups of patients. Remarkably, the sign of central shadow of pulmonary lobe distribution and cavity in TB‐DM group presented significantly higher rate than it in TB‐NDM group. Multivariable logistic regression showed that high uric acid level was an independent risk factor for thick wall cavity in TB‐DM patients (OR 2.81, 95% CI 1.24‐6.40), haemoptysis (OR 2.43, 95% CI 1.10‐5.38) and chest pain (OR 5.22, 95% CI 1.38‐19.70) were significantly associated with thick wall cavity.ConclusionsThe clinical features of TB‐DM patients are associated with cavities in CT scan, rather than DST results. It can help us recognition confounding variables, also may influence the treatment strategy and outcomes in TB‐DM patients.

Antihyperuricemic Effect of Dendropanax morbifera Leaf Extract in Rodent Models.

Dendropanax morbifera is a well-known traditional medicine used in China and Korea to treat intestinal disorders, urosis, diuresis, and chronic glomerulonephritis. Hyperuricemia is a metabolic disorder characterized by a high uric acid level in serum due to an imbalance between uric acid production and excretion and causes gout. Recently, the prevalence of hyperuricemia worldwide has been continuously increasing. Xanthine oxidase (XOD) inhibitors (allopurinol (ALP) and febuxostat) and uricosuric agents (benzbromarone and probenecid) are used to treat hyperuricemia clinically. However, because these drugs are poorly tolerated and cause side effects, such as kidney diseases, hepatotoxicity, gastrointestinal symptoms, and hypersensitivity syndrome, only a limited number of drugs are available. We investigated the antihyperuricemic effects of Dendropanax morbifera leaf ethanol extract (DMLE) and its underlying mechanisms of action through in vitro and in vivo studies. We evaluated uric acid levels in serum and urine, and xanthine oxidase (XOD) inhibition activity in the serum and liver tissue of a hyperuricemic rat model of potassium oxonate (PO)-induced hyperuricemic rats. In vitro study, XOD-inhibitory activity was the lowest among the test substances at the IC50 of ALP. However, the IC50 of DMLE-70 was significantly low compared with that of other DMLEs (p < 0.05). In PO-induced hyperuricemic rats, uric acid (UA) levels in serum and urine were significantly reduced in all DMLE-70 and allopurinol-treated (ALT) groups than in the PC group (p < 0.05). UA levels in urine were lower than those in serum in all DME groups. In PO-induced hyperuricemic rats, DMEE-200 reduced UA concentration in serum and increased UA excretion in the urine. These findings suggest that DMLE exerts antihyperuricemic and uricosuric effects on promoting UA excretion by enhanced secretion and inhibition of UA reabsorption in the kidneys. Thus, DMLE may be a potential treatment for hyperuricemia and gout.

Serum Uric Acid and Coronary Arterial Disease in Predialysis Chronic Kidney Disease Patients

Background–Aim: Uric acid is considered a marker of high cardiovascular risk. We investigated the association between serum uric acid and coronary arterial disease (CAD) in pre-dialysis chronic kidney disease (CKD) patients. Methods: We enrolled 110 subjects on mean age 69.02 ± 14.3 years old. The participants were categorized for both estimated glomerular filtration rate (eGFR) and albuminuria according to criteria 2012 of the Kidney Disease Improving Global Outcomes. Estimated pulse wave velocity (ePWV) was calculated using an equation including the age and mean blood pressure. The CAD prevalence rate was recorded. Results: The patients were divided in two groups according to uric acid cutoff point value related to high ePWV. The patients with higher uric acid were older and they had significantly higher systolic blood pressure, pulse pressure, and parathyroid hormone, but significantly lower eGFR and 1,25(OH)2 Vit D3 levels. The association between high uric acid and both high ePWV and CAD occurrence was found to be significant ( x2 = 6.7, P = .008 and x2 = 4.1, P = .03, respectively), although the relationship with albuminuria was found to be nonsignificant. In a built multifactorial model, the low serum uric acid rather than the high was found to be an independent predictor for CAD demonstration entering traditional and specific confounders. Conclusion: The low serum uric acid levels were proved to be a significant predictor for CAD accounting potential covariates, even though the high uric acid per se was found to be connected with cardiovascular disease characteristics including arterial stiffness in predialysis CKD patients.