Elevated Uric Acid Research Articles

Clinicopathologic predictors of renal response and survival in newly diagnosed multiple myeloma with renal injury: a retrospective study.

Renal impairment (RI) is a common complication of multiple myeloma (MM), which is associated with poor prognosis. Here, we revealed the association between regular examination data and RIincidence, RI response and survival in newly diagnosed multiple myeloma (NDMM) patients. A retrospective analysis was conducted on the initial clinical data of 647 NDMM patients, comprising 193 patients (29.83%, 193/647) with RI and 454 (70.17%, 454/647) without RI at diagnosis. Logistic regression analyses, both univariate and multivariate, were performed to identify the independent influencing factors of RI with bootstrap techniques and resampling. The model used to predict the RI response was established using the support vector machine-recursive feature elimination (SVM-RFE) machine learning algorithms. Six variables identified by multi-factorial logistic regression analysis were independently associated with the incidence of RI, including the secreted monoclonal immunoglobulin of IgG type (33.16% vs. 52.64%), deregulated serum free κ/λ light chain (58.12% vs. 33.93%), elevated serum calcium (> 2.65 mmol/L, 31.61% vs. 11.01%), elevated urea (≥ 8.3 mmol/L, 92.23% vs. 20.26%), elevated uric acid (≥ 340 μmol/L, 74.61% vs. 35.46%), and ISS (International Staging System) stage of III (90.16% vs. 31.50%). The lactate dehydrogenase (≥ 250 U/L; HR = 1.786, P = 0.005) and CKD (chronic kidney disease) stage (G4-G5; HR = 5.830, P = 0.016) were the independent adverse factors of the overall survival of NDMM patients with RI. In addition, this study provided a model to predict the response of RI using 5 clinical features, including calcium, Durie-Salmon (DS) stage, creatinine level before treatment, age and gender. The sensitivity, specificity, area under the curve (AUC) and accuracy were 86.75%, 51.15%, 78.30% and 72.99% in the training group, while 79.31%, 52.94%, 72.40% and 69.57% in the validation group. In conclusion, this study clarified the relationship between clinicopathologic characteristics and the incidence of renal injury, response and survival of NDMM patients, supporting clinical decision-making, and offering significant clinical application value.

Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria.

We investigated the role of uric acid in the pathogenesis of severe malaria (SM) in two independent cohorts of children with SM. Hyperuricemia (blood uric acid ≥ 7 mg dl-1) was present in 25% of children with SM and was associated with increased in-hospital mortality and postdischarge mortality in both cohorts. Increased blood uric acid levels were also associated with worse scores in overall cognition in children with SM < 5 years old in both cohorts. Hemolysis of infected red blood cells and impaired renal excretion of uric acid were the primary drivers of hyperuricemia in SM. Hyperuricemia was associated with multiple complications of SM, including acute kidney injury, acidosis, impaired perfusion, coma and intestinal injury with increases in the abundance of Gram-negative uricase-producing pathobionts (Escherichia and Shigella) in the stool. Clinical trials evaluating uric acid-lowering medications as adjunctive therapy for children with SM should be considered to improve survival and protect neurodevelopment.

P0416 Efficacy and safety of oral sulphate tablet for bowel preparation in patients with moderate to severe ulcerative colitis: a multicenter cohort study

Abstract Background Proper bowel preparation is essential factor for accurate, high-level colonoscopy. Poor bowel preparation has been reported in up to 30% of patients due to intolerance to high doses of preparation agent. Orafang [Pharmbiop Korea] is a novel sulphate tablet launched in Korea and is being used safely and effectively. According to a previous study, this oral sulphate tablet(OST) has shown effective bowel cleansing results and safety in patients with inactive IBD. However, data on efficacy and safety in patient with active UC are insufficient. We evaluated the efficacy and safety of OSTs in patients with moderate to severe UC. Methods Between January 2022 and July 2024, patients with UC who underwent bowel preparation with OST spilt-dose regimen were enrolled at the Inha university hospital, Samsung Changwon Hospital, and Konkuk University Medical Center. A total 63 patients were retrospectively reviewed. Patients were allocated by disease activity to inactive UC (n=39, 61.9%) or active UC (n=24, 38.1%). We reviewed clinical characteristics, bowel cleansing success rate defined as Boston bowel preparation scale (BBPS) ≥ 8 and safety as assessed by laboratory abnormalities and UC associated complications. Results Both the active and inactive inflammation groups showed high cleansing success rates as measured by the BBPS (87.5% vs. 89.7%, p=0.784), with no statistical difference. No clinically significant laboratory abnormalities were found in either group, except for elevations of uric acid above the upper limit observed in two inactive group patients. No endoscopy related complication or UC related hospitalizations occurred in either group. Conclusion OST was a low-volume agent for colonoscopy that demonstrated a safe and success bowel cleansing rate regardless of UC activity. Our study results suggest that the OST split-dose regimen is effective and safe even in patients with active UC. References Kim, Kyeong Ok, et al. "Efficacy, safety and tolerability of oral sulphate tablet for bowel preparation in patients with inflammatory bowel disease: A multicentre randomized controlled study." Journal of Crohn’s and Colitis 16.11 (2022): 1706-1713. Manes, Gianpiero, et al. "Appropriateness and diagnostic yield of colonoscopy in the management of patients with ulcerative colitis: a prospective study in an open access endoscopy service." Inflammatory bowel diseases 14.8 (2008): 1133-1138. Yang, Hyo-Joon, et al. "Novel sulfate tablet PBK-1701TC versus oral sulfate solution for colon cleansing: A randomized phase 3 trial." Journal of Gastroenterology and Hepatology 35.1 (2020): 29-36. Calderwood, Audrey H., et al. "Boston Bowel Preparation Scale scores provide a standardized definition of adequate for describing bowel cleanliness." Gastrointestinal endoscopy 80.2 (2014): 269-276.

Therapeutic potential and pharmacological mechanisms of Traditional Chinese Medicine in gout treatment.

Gout is a systemic metabolic disorder caused by elevated uric acid (UA) levels, affecting over 1% of the population. The most common complication of gout is gouty arthritis (GA), characterized by swelling, pain or tenderness in peripheral joints or bursae, which can lead to the formation of tophi. At present, western medicines like colchicine, febuxostat and allopurinol are the primary treatment strategy to alleviate pain and prevent flare-ups in patients with GA, but they have significant side effects and increased mortality risks. Traditional Chinese medicine (TCM) has been utilized for thousands of years for the prevention and treatment of GA, demonstrating effective control over serum UA (SUA) levels with fewer side effects. Herein we summarized a total of 541 studies published from 2000 to 2023 in sources including PubMed, Web of Science, the Cochrane Library and Embase, highlighting the therapeutic potential of TCM in treating gout and GA, particularly in combination with modern medical strategies. This review focuses on TCM formulas, Chinese herbal extracts, and active compounds derived from TCM, providing an overview of recent clinical application and the pharmacological research based on animal models and cellular systems. Particularly, the current review categorized the clinical and experimental evidence into the strategies for improving hyperuricemia, decreasing the sudden onset of acute GA and retarding chronic GA progression, supplied further coherent reference and enlightenment for clinicians, investigators of natural product chemistry, researchers in TCM and pharmacology. We hope this article will inspire the development of novel formulas and molecular entities for the treatment of gout and GA.

Association of homocysteine and uric acid with type 2 diabetes mellitus: a case-control study

The aim of this study was to examine the association between homocysteine (Hcy), uric acid (UA) and type 2 diabetes mellitus (T2DM), and to explore whether there was an interaction between Hcy and UA in the development of T2DM. A total of 1250 diabetic patients and 1250 non-diabetic controls were included in this case-control study. Binary logistic regression and interaction analysis were used to evaluate the association between Hcy, UA, and T2DM, and the combined effects of Hcy and UA on T2DM, respectively. Plasma Hcy and UA levels were significantly higher in diabetic patients compared to non-diabetic controls (p < 0.001, p = 0.002). Elevated Hcy and UA were risk factors for T2DM. Binary logistic regression analysis showed that compared with the lowest quartile of Hcy and UA, the highest quartile had a significantly increased risk of T2DM (OR = 1.629, 95% CI: 1.303, 2.035 for Hcy; OR = 1.596, 95% CI: 1.277, 1.995 for UA). Stratified analysis suggested a significant association between Hcy and T2DM for those aged < 65 years and males. A significant association between UA and T2DM was found in those aged ≥ 65 years, males, and BMI ≥ 24 kg/m2. No significant interaction was observed between Hcy and UA (p > 0.05). Hcy and UA were risk factors for T2DM. However, there was no interaction between Hcy and UA in the risk of T2DM.

Serum uric acid levels and intracerebral hemorrhage: A two-sample Mendelian randomization study.

Previous observational studies have generated controversy regarding the correlation between serum uric acid (UA) levels and intracerebral hemorrhage (ICH), with the causal relationship remaining uncertain. To assess the potential causal relationship between serum UA levels and ICH, two-sample Mendelian randomization analysis was applied. Single-nucleotide polymorphisms (SNPs) closely associated with serum UA were retrieved from the genome-wide association study (GWAS) database, including 580,505 individuals of European descent. A total of 27 and 251 SNPs were chosen as instrumental variables. Summary data for ICH included 1935 cases and 471,578 controls. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode methods, were employed to assess the potential causal relationship between serum UA levels and ICH, with odds ratios (ORs) as effect estimates. Heterogeneity was evaluated using Cochran's Q test, and sensitivity analyses were conducted using the leave-one-out method. The IVW analysis revealed that a 1 mg/dL increase in serum UA was associated with a 16.5 % higher risk of ICH (OR 1.165, 95 % CI 1.01-1.34, P = 0.034), while a 1 quantile increase in serum UA was associated with a 25.9 % higher risk (OR 1.259, 95 % CI 1.091-1.46, P = 0.002). Cochran's Q test showed no evidence of heterogeneity. No horizontal pleiotropy was detected. The sensitivity analysis using the leave-one-out method supported the robustness and reliability of our results. The study reveals that elevated serum UA levels are causally linked to ICH, suggesting the potential applicability of serum UA as a biomarker for the occurrence of ICH.

Elevated uric acid predicts increased coronary artery calcification risk in advanced chronic kidney disease: a cross-sectional study

Background Cardiovascular disease is the primary cause of morbidity and mortality in chronic kidney disease (CKD) patients, with vascular calcifications being a key predictor. Elevated serum uric acid (UA) has been implicated in vascular health, but its link with coronary artery calcification (CAC) in CKD is underexplored. This study evaluates the association between serum UA levels and CAC in predialysis CKD patients. Patients and methods This cross-sectional study at Mansoura University, Egypt, included 100 predialysis CKD patients aged over 40 years with more than 1 year of disease. Exclusion criteria included significant cardiovascular disease, pregnancy, heavy smoking, or high parathyroid hormone levels. Serum UA and other biomarkers were measured, and CAC was assessed using multislice spiral coronary computed tomography to calculate Agatston scores. Results The median age was significantly higher in the CAC&gt;0 group (62 years) compared to the CAC=0 group (55 years; P=0.017). Serum UA levels showed a borderline significant association with CAC in patients with an estimated glomerular filtration rate (eGFR) less than 30 ml/min/1.73 m2 (odds ratio: 1.26, 95% confidence interval: 1.01–1.61, P=0.051), but no significant association was found in those with moderate kidney impairment (eGFR 30–59 ml/min/1.73 m2). Conclusion Elevated serum UA levels are associated with an increased risk of CAC in CKD patients, particularly in those with severe renal impairment (eGFR&lt;30 ml/min/1.73 m2). This suggests that serum UA may contribute to this population’s pathogenesis of vascular calcification.

Application Value of STOP-Bang Questionnaire in Predicting Abnormal Metabolites.

To evaluate the application value of STOP-Bang questionnaire (SBQ) in predicting abnormal metabolites. Totally 121 patients were included into the study and filled the questionnaires, and their clinical data were collected at the same time. These patients were grouped according to the questionnaire scores. The clinical data of patients in various groups were compared using R4.3.1 statistical software. Based on the SBQ score, the patients were divided into the following groups: low-risk group (0-2 scores), mid-risk group (3-4 scores), and high-risk group (5-8 scores). SBQ score was related to several abnormal metabolites. A higher SBQ score indicated elevated uric acid (UA), waist circumference (WC), fasting blood glucose (FBG), hemoglobin A1c (HbA1c) and triacylglycerol (TG), but notably lower high density lipoprotein-cholesterol (HDL-C). In respect of liver function, alanine aminotransferase (ALT) and aspartate transaminase (AST) were both in low/mid-risk group than in high-risk group. With respect to renal function, there was a statistically significant difference in serum creatinine (SCr) (lowest in the low-risk group and highest in the high-risk group) but no such difference in estimated glomerular filtration rate (eGFR) among the three groups. The diagnosability analysis showed that the AUROC proved the good performance of SBQ in predicting metabolic syndrome (MetS) and hyperuricemia (HUA). OSA frequently co-occurs with various metabolic disorders. SBQ, a widely used tool for assessing the risk of OSA, may also be a potential tool for predicting the presence of metabolic diseases. A higher SBQ score indicates a heightened susceptibility to more abnormal metabolites, but SBQ is poor in predicting liver and renal functions. The patients with SBQ score ≥3 are suggested to pay a visit to the Endocrine Department and Sleep Disorders Center for a comprehensive evaluation of comorbid Obstructive sleep apnea (OSA) and the management of systematic metabolism.

Serum Albumin and Uric Acid Levels in Hypertensive Patients: A Cross-Sectional Analysis From Central Tamil Nadu, South India.

Introduction Hypertension represents a significant global health challenge, with an increasing incidence among adults. Despite the prominence of infectious diseases, non-communicable conditions like hypertension remain a silent yet critical health concern. Liver and kidney functions play crucial roles in blood pressure maintenance, with serum albumin and uric acid serving as key metabolic indicators. Objective The primary objective of this study is to analyze the association between serum albumin and uric acid levels in hypertensive patients aged 30-50 years. The secondary objective is to determine whether deranged serum albumin and uric acid levels are associated with other variables like body mass index and blood pressure values. Methods An analytical cross-sectional study was conducted between September and October 2021 at a hospital in Perambalur, Tamil Nadu, India. The study employed non-probability convenient sampling to recruit hypertensive patients aged 30-50 years. Participants with coronary artery disease, stroke, liver disease, renal failure, hyperuricemia, gout, diabetes mellitus, or taking medications that affect albumin or uric acid levels were excluded. Blood pressure measurements were taken after ensuring adequate rest, and 4 ml of venous blood was collected from each participant for biochemical analysis. Serum albumin and uric acid levels were determined using the analyzer. The data analysis was performed using Microsoft Excel and statistical software. The statistical significance of the findings was evaluated using appropriate statistical tests, providing a robust framework for understanding the metabolic associations in hypertension. Results The study population of 150 hypertensive patients demonstrated a majority of 88 (58.67%) aged over 40 years and 62 (41.33%) under 40 years. The gender distribution revealed 87 (58%) males and 63 (42% females). The mean systolic blood pressure was 158.2 mmHg, with a mean diastolic blood pressure of 94.73 mmHg, indicating moderate to severe hypertension. Biochemical analysis showed an average serum uric acid level of 6.41 mg/dL and a mean serum albumin level of 3.54 mg/dL. Statistical analysis revealed a significant association between elevated uric acid levels and decreased serum albumin levels (p < 0.05), suggesting a potential interrelationship between these metabolic markers in hypertensive patients. Conclusion The study establishes hyperuricemia and hypoalbuminemia as significant risk factors for hypertension development or pathogenesis. Early detection of these metabolic derangements may provide opportunities for preventive interventions and potential disease management strategies. The findings emphasize the importance of comprehensive biochemical assessment in understanding and mitigating hypertension risk.

Elevated uric acid levels are associated with an increased risk of fibrosis in MASLD

Elevated uric acid levels are associated with an increased risk of fibrosis in MASLD

Establishment and optimization of a novel mouse model of hyperuricemic nephropathy

Hyperuricemia is a metabolic disorder characterized by elevated serum uric acid levels. Soluble urate can activate immune responses, and the excessive accumulation of urate in the kidneys results in hyperuricemic nephropathy (HN). However, the lack of an established HN model is a major obstacle to advancing research into the pathogenesis of HN and the development of novel drugs. In this study, we generated and evaluated an optimized mouse model of HN by the combined administration of potassium oxonate and hypoxanthine at various dosages. Our results demonstrated that intraperitoneal injection of 200 mg/kg potassium oxonate with gavage of 500 mg/kg hypoxanthine caused renal injury in mice, as evidenced by the elevation in serum uric acid, serum creatinine, and 24 h albuminuria levels, as well as pathological changes in renal histology. Intraperitoneal injection of 200 mg/kg potassium oxonate with gavage of 500 mg/kg hypoxanthine markedly increased the production of uric acid, inhibited uricase activity, and disrupted uric acid transporters. This led to supersaturated urate deposition in the kidneys, triggering renal inflammation and fibrosis, thereby promoting HN progression. In conclusion, we successfully established a stable and efficient mouse model that can mimic the pathogenesis of HN. This novel model may facilitate the discovery of therapeutic targets and the development of new drugs for the treatment of HN.

Risk factors for metabolic syndrome in the premetabolic state assessed using hierarchical clustering study in a health screening group

Early detection of a premetabolic status that is at risk for metabolic syndrome (MetS) but not meeting the criteria is crucial. This study examined 27,623 participants aged 20–50 (mean: 40.7) years who underwent initial health screening at Kangbuk Samsung Hospital (2011–2019), focusing on individuals with one or two MetS components. Hierarchical agglomerative clustering was used to form MetS risk clusters based on initial and follow-up data, including age, resting heart rate (rHR), serum uric acid (UA), C-reactive protein (CRP), gamma-glutamyl transpeptidase, and ferritin levels, and nonalcoholic fatty liver disease (NAFLD), periodontal disease, and Helicobacter pylori infection duration. Kaplan–Meier and generalized additive models were used to present the restricted mean survival time (RMST) and identify onset contributors. Clusters with NAFLD and elevated UA levels had the highest MetS risk, whereas those with uniformly low biomarker levels revealed the lowest risk. During follow-up, a cluster initially comprising 60.2% moderate-risk patients exhibited high biomarker levels and had the worst MetS prognosis (RMST: 211 days). UA, CRP levels, and rHR contributed to the incidence of MetS in the fitted model. Machine learning can predict the premetabolic state at MetS risk in a population-based cohort.

Gouty arthritis patients’ diagnostic, biochemical, and hematological characteristics study: a single-center retrospective study

ObjectiveThis study aims to investigate the diagnostic, biochemical, and hematological characteristics of patients with gouty arthritis and analyze their correlations with baseline characteristics to guide clinical practice, develop personalized treatment strategies, and improve patient outcomes.MethodsA single-center retrospective analysis was conducted on 8,344 patients with acute gouty arthritis admitted to our hospital between January 2014 and December 2023. Baseline characteristics and laboratory data, including uric acid, blood glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), C-reactive protein (CRP), white blood cell count, neutrophil count, lymphocyte count, monocyte count, fibrinogen, and serum albumin, were collected. General linear and Pearson correlation analyses were performed to identify significant relationships.ResultsSignificant correlations were observed between baseline characteristics (age, body mass index (BMI), smoking, and drinking status) and uric acid levels. High uric acid levels were positively correlated with inflammatory markers (hs-CRP, white blood cell count, and neutrophil count) and metabolic indicators (triglycerides, LDL-C, and creatinine) but negatively correlated with HDL-C. Notable differences in blood and biochemical indicators were identified across age, gender, and BMI groups.ConclusionThis study highlights key laboratory characteristics of gouty arthritis, emphasizing the need for individualized treatment strategies. Comprehensive interventions focusing on managing inflammation and metabolic disturbances in patients with elevated uric acid levels are critical for optimizing prognosis and improving quality of life.

Dynamics of uric acid concentration against the background of early dapagliflozin use in patients with acute decompensation of heart failure

Background. Acute decompensation of heart failure (ADHF) is an urgent problem of modern cardiology due to unfavourable prognosis and high frequency of repeated hospitalizations. The risk of acute kidney injury in patients with ADHF, which significantly worsens clinical outcomes, is high, including due to elevated uric acid levels. Aim. To evaluate the effect of sodium-glucose cotransporter type 2 inhibitor dapagliflozin in patients with ADHF with reduced left ventricular ejection fraction (LVEF) on uric acid levels. Materials and methods. The study included 122 patients with ADHF and reduced LVEF (28±6%), III FC 97 (79.5%) patients and II FC 25 (20.5%). All patients received therapy for ADHF according to available guidelines. Patients were divided into two groups: the first group standard therapy, patients in the second group were added dapagliflozin at a dose of 10 mg to standard therapy. Dapagliflozin was administered on average on the 2nd day (1–3) from admission to the hospital on condition of stable haemodynamics. The duration of follow-up was 6 months. The level of uric acid, creatinine, glomerular filtration rate, NT-proBNP, CRP and ST2 at the time of inclusion in the study and 6 months after hospital discharge were analysed. Results. In patients with ADHF and reduced LVEF, a uric acid level equal to or greater than 667.9 μmol/L during hospitalisation predicted a high risk of death during the 6-month follow-up period. Decrease of uric acid level was observed only on the background of dapagliflozin therapy 472 (366–594) μmol/L initially, 326 (275–419) μmol/L when ADHF compensation was achieved (p0.001), after 6 months the significant changes remained – 359 (263–410) μmol/L (p0.001). Against the background of dapagliflozin therapy there was a significant decrease in NT-proBNP level after 6 months from 2059 pg/ml (1456–4204.5) to 1101 pg/ml (415.8–3371.5); p0.006; decrease in ST2 concentration after 6 months from 24. 4 ng/ml (15.1–35) to 19.4 ng/ml (13.3–30.1); p0.041; decrease in SRP after six months from 2.9 mg/L (1.2–7.1) to 2.1 mg/L (0.9–2.8); p0.015; no worsening of renal function was noted. Conclusion. It can be concluded that dapagliflozin has a favourable safety and efficacy profile when used in patients with ADHF and hyperuricemia.

Elevated uric acid level and metabolic syndrome in Non-Hispanic Black American adults.

To ascertain the direct and indirect link between elevated uric acid (eUA) and metabolic syndrome (MetSyn) in Non-Hispanic Black (NHB) American adults. Structural equation modeling (SEM) was used to disentangle the U.S. National Health and Nutritional Examination Survey (2015-2018 NHANES) dataset and investigate the connection between eUA and components of MetSyn as per the criteria from the National Cholesterol Education Program (NCEP) Adult Treatment Panel III. The association between eUA and MetSyn was determined using odds ratios from sex-specific multivariable logistic regression analysis. The analysis was adjusted for age, physical activity, alcohol use, and smoking. SEM coefficients were used to measure the strength of the link between eUA and MetSyn components. NHB American men with eUA had 1.41-fold greater odds of MetSyn, and NHB American women with eUA had 2.70-fold greater odds of MetSyn after adjusting for confounding factors. Elevated uric acid was more strongly and directly linked to abdominal obesity (β = 0.320, p < 0.01) in NHB American men, and with abdominal obesity (β = 0.423, p < 0.01), dyslipidemia (β = 0.151, p < 0.01) and hypertension (β = 0.121, p < 0.01) in NHB American women than between eUA and other components of MetSyn. This study's finding linking eUA to MetSyn components in NHB American adults needs reaffirmation through a robust prospective study design. If validated, eUA could help predict and prevent MetSyn in NHB American adults.

Assessment of Subacute Toxicity of Ulexite in Rats: Behavioral, Hematological, and Biochemical Insights.

Ulexite (UX), a naturally occurring borate mineral, has gained interest for its diverse industrial applications, yet its toxicological profile remains inadequately characterized. This study aimed to evaluate the subacute toxicity of UX in rats, focusing on behavioral, hematological, and biochemical parameters. Rats were administered UX via gavage at doses of 10, 30, and 300mg/kg for 7days. No mortality or significant signs of toxicity were observed, although body weight measurements indicated a notable reduction in the UX-treated groups compared to controls. Behavioral assessments demonstrated increased exploratory activity in the 10 and 300mg/kg UX treated groups, suggesting low anxiety levels. Likewise, hematological analysis revealed that 30 and 300mg/kg UX led a significant (P < 0.001) increase in hematocrit and a decrease in mean corpuscular hemoglobin concentration (P < 0.001), indicating potential changes in erythropoiesis. Additionally, serum biochemistry showed elevated aspartate aminotransferase (P < 0.05), lactate dehydrogenase (P < 0.001), and uric acid levels (P < 0.01), suggesting liver stress. Histopathological examinations indicated dose-dependent alterations, with mild hepatocellular degeneration and neuronal changes observed at the highest dose. Also, MN levels in the blood of rats exposed to 10 and 30mg/kg UX showed no significant differences. These results suggest that UX is relatively safe at lower doses, though higher exposures may pose health risks. Further research is warranted to elucidate the mechanisms underlying UX-induced effects and to evaluate its safety for therapeutic and occupational applications.

Associations of systemic inflammation and systemic immune inflammation with serum uric acid concentration and hyperuricemia risk: the mediating effect of body mass index

BackgroundWith the development of lifestyle, elevated uric acid and hyperuricemia have become important factors affecting human health, but the biological mechanism and risk factors are still unclear.MethodsA multi-stage, cross-sectional study of 41,136 adults from the NHANES 2003-2018 was conducted. Serum uric acid concentrations, platelet, neutrophil, lymphocyte, and monocyte counts were measured. The systemic inflammation response (SIRI) index and systemic immune-inflammatory (SII) index were calculated to reflect systemic inflammation and systemic immune inflammation. The height and weight data were obtained to assess body mass index (BMI). Generalized linear models were used to examine the relationships of SIRI and SII with uric acid and hyperuricemia risk, as well as the associations of SIRI and SII with BMI, and BMI with uric acid and hyperuricemia risk. Causal mediation effect model was used to assess the mediating effect of BMI in the relationships of SIRI, and SII with uric acid concentration and hyperuricemia risk.ResultsThe prevalence of hyperuricemia in US adults is 19.78%. Positive associations were found in the relationships of SIRI and SII with uric acid level, hyperuricemia risk, and BMI, as well as the relationships of BMI with uric acid and hyperuricemia risk. Causal mediation effect model showed that BMI played an important mediating role in the relationships of SIRI, and SII with uric acid concentration and hyperuricemia risk, with the proportion of mediating effect ranging from 23.0% to 35.9%.ConclusionExposure to higher SIRI and SII is associated with increased uric acid concentration and hyperuricemia risk in adults, and BMI plays an important mediating effect. Reducing systemic inflammation and systemic immune inflammation and proper weight control could be effective ways to reduce hyperuricemia prevalence and related health problems.

Hyperuricemia Is Associated With Higher Mortality in Non-diabetic Heart Failure Patients.

Hyperuricemia (HU) is associated with an increased risk of incident heart failure (HF) and adverse HF outcomes. Patients with diabetes mellitus (DM) have a greater prevalence of HU. We evaluated the prognostic impact of HU in patients with HF according to the coexistence of DM. A retrospective cohort study of ambulatory patients with HF with left ventricular systolic dysfunction (LVSD) was conducted from January 2012 to May 2018. The end point was all-cause mortality; follow-up was until January 2021. A Cox regression analysis was used to assess the prognostic impact of elevated uric acid (UA) levels. The cut-off for HU was 8.2 mg/dL. A multivariate model was built accounting for confounders. The analysis was stratified according to DM, and interaction between DM and UA levels was tested. We studied 538 patients, of whom 66% were males. Of the patients, 45% had ischemic HF, 41% had DM, and11% were receiving urate-lowering therapies. The median (interquartile range (IQR)) admission UA was 5.5 (5.8-9.2) mg/dL, and 40% had UA > 8.2 mg/dL. During a median 46-month follow-up, 48.5% of patients died. Patients with UA > 8.2 mg/dL had a multivariate-adjusted hazard ratio (HR) (95% confidence interval (CI)) of all-cause mortality of 1.75 (1.20-2.55; p=0.003). The interaction between DM and UA levels was significant (p=0.04). The independent association of hyperuricemia with mortality persisted only in non-DM patients (HR: 1.70, 95% CI: 1.16-2.51; p=0.007). In those with DM, hyperuricemia portended no survival disadvantage. DM appears to influence the prognostic impact of HU in chronic HF. The risk of all-cause mortality in hyperuricemic HF patients without DM increases by 70% when compared with those with normal UA levels.

The Role of Beta-Hydroxybutyrate in Mitigating the Inflammatory and Metabolic Consequences of Uric Acid.

Background: Uric acid (UA), a metabolite of purine and fructose metabolism, is linked to inflammation and metabolic disorders, including gout and cardiovascular disease. Its pro-inflammatory effects are largely driven by the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, leading to increased cytokine production. Beta-hydroxybutyrate (BHB), a ketone produced during fasting or carbohydrate restriction, has been shown to reduce inflammation. This study explores the role of BHB in mitigating the inflammatory and metabolic effects of elevated uric acid levels. Methods: We utilized a murine muscle cell culture treated with UA and BHB. Results: Muscle cells treated with UA had increased production of pro-inflammatory cytokines and reduced cell viability. Co-treatment with BHB reversed these effects, improving cell survival and reducing cytokine levels. Additionally, uric acid impaired mitochondrial function and increased oxidative stress, which were mitigated by BHB. Furthermore, uric acid disrupted insulin signaling, but BHB co-treatment restored insulin sensitivity. Conclusions: These findings suggest that BHB holds therapeutic potential by counteracting the inflammatory and metabolic disruptions caused by elevated uric acid, making it a promising target for conditions such as hyperuricemia and metabolic syndrome.

Soy Protein and Safflower-Seed Oil Attenuate Inflammation and Immune Dysfunction in Rats with Hyperuricemia.

A plant-based diet is considered a promising approach for managing hyperuricemia (HUA). This study examined the effects of soy protein and plant-based oils on HUA-induced inflammation and immune dysfunction. Male Wistar rats, induced with HUA using oxonic acid and uric acid (UA), were fed casein or soy protein with palm or safflower oil (2 × 2 factorial design) for 8 weeks. HUA rats had lower serum albumin and T cell percentages in peripheral blood leukocytes (PBLs) and splenocytes, along with increased leukocyte counts and spleen weights, compared to healthy rats (p < 0.05). Soy protein improved HUA-induced reductions in albumin, while safflower-seed oil ameliorated reductions in albumin, plasma interleukin (IL)-4, and T-suppressor splenocytes, and mitigated elevated serum UA, plasma IL-6, and B leukocytes (two-way ANOVA, p < 0.05). In PBL, soy protein alleviated HUA-induced decreases in TNF-α, casein and palm oil increased IL-6, and casein further reduced IFN-γ production. Under Con A stimulation, casein and safflower-seed oil alleviated decreases in IL-6 and IL-10, respectively, while under LPS stimulation, casein further increased TNF-α production. In splenocytes, soy protein and safflower-seed oil reduced HUA-induced increases in TNF-α and increased IL-10, and safflower-seed oil increased IL-6 production. Under Con A stimulation, soy protein and safflower-seed oil reduced TNF-α and increased IL-10 production in splenocytes. The findings suggest that soy protein and safflower-seed oil may counteract HUA-related inflammation, alleviate monocyte activation, and enhance Th2 immune response in HUA. A plant-based diet rich in soy protein and safflower-seed oil may help manage HUA and associated inflammation and immune dysfunction.