Reduced Serum Uric Acid Research Articles

Wearable Hydrogel SERS Chip Utilizing Plasmonic Trimers for Uric Acid Analysis in Sweat.

Uric acid is typically measured through blood tests, which can be inconvenient and uncomfortable for patients. Herein, we propose a wearable surface-enhanced Raman scattering (SERS) chip, incorporating a hydrogel membrane with integrated plasmonic trimers, for noninvasive monitoring of uric acid in sweat. The plasmonic trimers feature sub 5 nm nanogaps, generating strong electromagnetic fields to boost the Raman signal of surrounding molecules. Simultaneously, the hydrogel membrane pumps sweat through these gaps, efficiently capturing sweat biomarkers for SERS detection. The chip can achieve saturation adsorption of sweat within 5 min, eliminating variations in individual sweat production rates. Dynamic SERS tracking of uric acid and lactic acid levels during anaerobic exercise reveals a temporary suppression of uric acid metabolism, likely due to metabolic competition with lactic acid. Furthermore, long-term monitoring correlates well with blood test results, confirming that regular exercise helps reduce serum uric acid levels and supporting its potential in managing hyperuricemia.

Omega-3 polyunsaturated fatty acids alleviate hyperuricemic nephropathy by inhibiting renal pyroptosis through GPR120

Hyperuricemic nephropathy (HN) is characterized by increased serum uric acid levels that incite renal inflammation. While omega-3 polyunsaturated fatty acids (PUFAs) are known for their anti-inflammatory properties, their impact on HN remains unclear. This study explored the effects of omega-3 PUFAs, specifically docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on HN. Using a mouse model induced by adenine and potassium oxonate, we treated HN mice with DHA, EPA, or both for four weeks. The results showed that omega-3 PUFAs significantly reduced serum uric acid levels and improved kidney function, with DHA, EPA, and their combination showing similar efficacy. Transcriptome sequencing and further analysis revealed that these fatty acids alleviate renal pyroptosis by reducing key markers such as NOD-like receptor pyrin containing 3 (NLRP3), cleaved gasdermin-D, caspase-1, and interleukin-1β. To further investigate the underlying mechanism, we focused on G-protein coupled receptor 120 (GPR120), a receptor activated by DHA. The use of a GPR120 antagonist (AH7614) partially blocked DHA’s effects, while the agonist (TUG891) mimicked its anti-pyroptotic actions. Co-immunoprecipitation assays showed that DHA activates GPR120, leading to its internalization and interaction with β-arrestin2, ultimately inhibiting NLRP3 inflammasome formation and reducing inflammation. Overall, omega-3 PUFAs, particularly through GPR120 activation, appear to protect against renal inflammation in HN by modulating the NLRP3/caspase-1/GSDMD pathway.

Clinical characteristics and management of adipsic arginine vasopressin deficiency in children and adolescents with sellar germ cell tumors.

Adipsic arginine vasopressin deficiency(aAVP-D) is a rare, high-risk syndrome, particularly difficult to recognize and manage in children and adolescents. This investigation examined the clinical features and management of aAVP-D in children and adolescents with sellar germ cell tumors (GCTs). A retrospective survey was performed on 260 patients with sellar GCTs, categorized into aAVP-D and non-aAVP-D groups based on thirst presence. General characteristics, hypothalamic syndrome, pituitary function, metabolic indicators, and complications were compared. Biochemical indicator changes in the aAVP-D group were analyzed after systematic management, and receiver operating characteristic (ROC) curve analysis established the optimum serum sodium cut-off for predicting the aAVP-D. 25 patients (9.6%) developed aAVP-D. The aAVP-D group had larger tumors with hypothalamic involvement and more surgical resections. They also demonstrated more hypothalamic syndrome, central adrenal insufficiency, central hypogonadism, and insulin-like growth factor-1 levels below norms. Furthermore, aAVP-D patients exhibited significantly higher rates of hypernatremia (100% vs 20.9%, p < 0.001), hyperuricemia (60.0% vs 23.4%, p < 0.001), renal impairment (32.0% vs 1.7%, p < 0.001), and venous thrombosis (4.0% vs 0%, p = 0.002). Following systematic management, aAVP-D patients experienced significant reductions in serum sodium, uric acid, and creatinine levels, although these remained higher than in the non-aAVP-D group. ROC analysis indicated that a serum sodium level above 149.5mmol/L predicted aAVP-D. Conclusion Patients with aAVP-D had more tumor involvement in the hypothalamic region, surgical resections, hypothalamic syndrome, hypopituitarism, and complications. Serum sodium levels above 149.5mmol/L necessitated heightened vigilance for aAVP-D. Early identification and systematic management reduced complications, though clinical management remained challenging. What is Known •Adipsic arginine vasopressin deficiency (aAVP-D) is a rare and high-risk syndrome that is difficult to recognize and manage. •There are few reports on aAVP-D, most of which focus on adult patients. •The characteristics and management of aAVP-D in children and adolescents remain unclear. What is New •Children and adolescents with aAVP-D experienced higher rates of hypothalamic region tumor involvement, surgical resections, hypothalamic syndrome, hypopituitarism, and associated complications. •Serum sodium levels above 149.5mmol/L necessitated heightened vigilance for aAVP-D. •Early recognition and structured management of ADI lowered the risk of complications.

Uric Acid and SGLT2 Inhibition With Empagliflozin in HeartFailure With Preserved Ejection Fraction: The EMPEROR-Preserved Trial.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve outcome in patients with heart failure (HF) and reduce serum uric acid (SUA). The relevance of this metabolic effect in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. The authors investigated the effect of empagliflozin on SUA levels in relation to the therapeutic efficacy in patients with HFpEF. This post hoc analysis of the EMPEROR-Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction; NCT03057951) trial assessed the clinical effect of SUA reduction in relation to the outcome endpoints of the trial (composite primary outcome of cardiovascular mortality or hospitalization for HF, its individual components, and all-cause mortality in patients with HFpEF). Hyperuricemia (SUA >5.7mg/dL for women, >7.0mg/dL for men) was prevalent in 49% of patients. Elevated SUA (highest tertile SUA 8.8 ± 1.4 g/dL) was associated with advanced HF severity and with higher risk of adverse outcome (primary endpoint HR: 1.23 [95%CI: 0.98-1.53]; P = 0.07; HF hospitalization HR: 1.42 [95%CI: 1.08-1.86]; P= 0.01). SUA was reduced early (after 4weeks vs placebo-0.99 ± 0.03mg/dL; P< 0.0001) and throughout follow-up, with reduction in all prespecified subgroups. Empagliflozin reduced clinical events of hyperuricemia (acute gout, gouty arthritis, or initiation of antigout therapy) by 38% (HR: 0.62 [95%CI: 0.51-0.76]; P< 0.0001). The treatment benefit on the primary endpoint was not influenced by baseline SUA (HR: 0.79 [95%CI: 0.69-0.90]; P = 0.0004). The change in SUA was an independent correlate of the treatment benefit on the primary endpoint (P = 0.07). Hyperuricemia is a common complication in HFpEF and is related to advanced disease severity and adverse outcome. Empagliflozin induced a rapid and sustained reduction of SUA levels and of clinical events related to hyperuricemia.

Pegloticase-Induced Rapid Uric Acid Lowering and Kidney and Cardiac Health Markers in Youth-Onset Type 2 Diabetes: A Pilot Clinical Trial

Rationale & ObjectiveElevated serum uric acid (SUA) is a risk factor for incident hypertension and diabetic kidney disease in young persons with type 2 diabetes (T2D), particularly men. The acute benefit of aggressively lowering SUA on kidney and cardiovascular function in this population remains underexplored. This study was conducted to investigate the impact of a single pegloticase infusion on kidney and cardiovascular function. Study DesignAn open-label pilot trial. Setting & ParticipantsThe study involved 10 young adult males with youth-onset T2D and SUA levels ≥5 mg/dL. Intervention(s)Participants received a single infusion of pegloticase (8 mg). Evaluations were conducted using iohexol-based measured glomerular filtration rate (mGFR) and cardiac/kidney MRI before and one week after infusion. OutcomesThe primary outcomes were changes in SUA and mGFR one week after pegloticase infusion. ResultsNine participants (mean [±SD] age 22±5 years, HbA1c 8.6±3.3%, BMI 40.1±11.0 kg/m2, SUA 6.7±1.1 mg/dL) completed the pegloticase infusion and were included in the analysis. One week after the infusion, median [p25,p75] SUA concentrations dropped from 6.4 [5.6,7.6] to 0.5 [0.5,4.6] mg/dL (p=0.01). Mean mGFR increased from 113±20 to 122±19 ml/min per 1.73 m2 (p=0.004). Among responders (SUA reduction ≥3 mg/dL), an increase in mGFR correlated with an increase in renal artery blood flow (r:0.60, p=0.24) and decrease in SUA (r:-0.79, p=0.05). Mean MRI peak longitudinal cardiac strain additionally decreased from 15.4±2.2 to 13.1±2.2 % (p=0.03) in these responders. LimitationsThe pilot nature of the study and the small sample size limit the generalizability of the findings. ConclusionsIn young adult males with T2D, a single pegloticase infusion decreased SUA levels, which increased mGFR and was strongly associated with increased renal blood flow and impaired cardiac global longitudinal strain. Further research is required to assess the long-term efficacy and safety of pegloticase in patients with T2D.

Integrating metabolomics with network pharmacology to reveal the mechanism of Poria cocos in hyperuricemia treatment

Ethnopharmacological relevanceHyperuricemia is a chronic condition characterized by persistently elevated uric acid levels, often leading to gouty arthritis and renal insufficiency. Poria cocos F.A.Wolf, a traditional Chinese medicinal herb, possesses notable diuretic and anti-inflammatory properties and is widely used to treat edema, inflammation, viral infections, and tumors. Recent studies suggest that Poria cocos has the potential to lower uric acid levels and mitigate kidney damage, making it a promising candidate for hyperuricemia treatment. However, its pharmacological mechanisms require further exploration. Aim of the studyThis study aims to elucidate the mechanisms by which Poria cocos alleviates hyperuricemia, using metabolomics and network pharmacology approaches. Materials and methodsHyperuricemia was induced in rats via a high-yeast diet combined with potassium oxonate. The effects of Poria cocos were assessed by measuring serum uric acid, creatinine, urea nitrogen levels, hepatic xanthine oxidase activity, and renal tissue morphology. Non-targeted metabolomics was employed to identify differential metabolites and explore the metabolic pathways involved in its therapeutic effects. Network pharmacology was utilized to analyze potential targets and signaling pathways, which were validated through molecular docking and ELISA analysis. ResultsPoria cocos extract significantly reduced serum uric acid, creatinine, and urea nitrogen levels, inhibited xanthine oxidase activity, and attenuated kidney damage. Metabolomics combined with network pharmacology identified xanthine dehydrogenase and fatty acid synthase as key targets, while purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis were identified as critical pathways. ELISA confirmed that Poria cocos suppressed xanthine dehydrogenase and fatty acid synthase expression in hyperuricemic rats. Molecular docking further verified strong binding interactions between core compounds and key targets. ConclusionsPoria cocos alleviates hyperuricemia by modulating multiple compounds, targets, and pathways. Through network pharmacology and metabolomics, it reveals that Poria cocos selectively regulates xanthine dehydrogenase and fatty acid synthase, influencing purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis pathways. These findings provide insights into its therapeutic mechanisms, supporting the clinical application of Poria cocos in treating metabolic disorders and kidney damage associated with hyperuricemia.

Discovery of 4-(isopentyloxy)-3-nitrobenzamide derivatives as xanthine oxidase inhibitors through a non-anthraquinone exploration.

In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 μM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC50, along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration.

Serum uric acid-lowering effect of sacubitril/valsartan in hypertensive patients: evaluation by switching from angiotensin II receptor blockers.

Since hyperuricemia is a risk factor for cardiovascular disease and chronic kidney disease, it is necessary to pay attention to trends in uric acid levels when treating hypertensive patients with drugs. The present study investigated the effect of switching from angiotensin II receptor blocker (ARB) to sacubitril/valsartan on serum uric acid levels in treated hypertensive patients and further examined what factors could be associated with its effect. In 75 hypertensive patients under treatment with at least one antihypertensive agent including ARB, clinic blood pressure and biochemical parameters were assessed before and after drug switching to sacubitril/valsartan (200 mg/day). Clinic SBP and DBP significantly decreased after drug switching to sacubitril/valsartan (P < 0.0001, respectively). Serum creatinine, estimated glomerular filtration rate (eGFR), and urinary protein did not change after switching to sacubitril/valsartan, but serum uric acid significantly decreased (5.70 ± 1.44 to 5.40 ± 1.43 mg/dl, P = 0.0017). The degree of uric acid lowering was greater in patients switching from ARB plus diuretic than in those switching from ARB, but switching to sacubitril/valsartan from ARB only (except losartan) also significantly decreased uric acid levels. In all subjects, the change in serum uric acid after drug switching to sacubitril/valsartan was closely correlated with the change in eGFR (r = -0.5264, P < 0.0001). Our findings indicate that switching from ARB to sacubitril/valsartan reduces serum uric acid levels in hypertensive patients and suggest that this uric acid-lowering effect may be associated with an increase in eGFR.

Empowering probiotics with high xanthine transport for effective hyperuricemia management

ABSTRACT Hyperuricemia, a prevalent metabolic disorder, poses a susceptibility to various complications. The conventional pharmacotherapeutic approaches for hyperuricemia often entail notable adverse effects, posing substantial clinical challenges. Hence, the imperative lies in the development of novel, safe and effective strategies for preventing and treating hyperuricemia. Here, we developed a probiotic Escherichia coli Nissle 1917 strain, designated as YES301, which contains a rationally designed xanthine importer XanQ, enabling efficient uptake of xanthine and hypoxanthine, consequently leading to reduced serum uric acid concentrations and amelioration of renal impairments in a murine model of hyperuricemia. Importantly, YES301 exhibited a therapeutic efficacy comparable to allopurinol, a conventional uric acid-lowering agent, and manifesting fewer adverse effects and enhanced biosafety. These findings highlight the promising potential of engineered probiotics in the management of hyperuricemia through reducing intestinal purine levels.

Mechanism of Biqi capsules in the treatment of gout based on network pharmacology and experimental verification

Ethnopharmacological relevanceGout is a crystal-related arthropathy caused by monosodium urate (MSU) deposition, resulting from purine metabolism disorders and hyperuricemia (HUA). Gout belongs to the traditional medicine category of Bi syndrome. Biqi capsules (BQ) is a traditional Chinese medicine formula used to treat Bi syndrome. The BQ prescription is derived from the ancient prescription of Hua Tuo, a famous physician in the Han Dynasty. Aim of the studyTo study the effect and mechanism of BQ in treating acute gouty arthritis (AGA) and HUA. Materials and methodsAnalyzing BQ's signaling pathways for gout treatment via network pharmacology. The HUA model was induced orally with adenine and potassium oxonate. The rat AGA model was established by MSU injection. In vitro, MH7A and RAW 246.7 cells were treated with LPS and MSU. Serum uric acid, creatinine, and urea nitrogen levels were evaluated. Kidney and ankle joint pathology was observed via HE staining. Inflammatory signaling pathway proteins, epithelial-mesenchymal transition (EMT) pathway proteins, and uric acid metabolism-related proteins were detected by Western blot. Results1780 potential targets for gout treatment were identified, and 1039 target proteins corresponding to BQ's active ingredients were obtained. Pathway enrichment analysis revealed BQ improved gout mainly through inflammatory pathways. Experimental results showed BQ could reduce serum uric acid level and increase uric acid clearance rate by regulating the expression of adenosine deaminase (ADA), and organic anion transporter 1 (OAT1) and glucose transporter 9 (GLUT9) in HUA mice. BQ could improve renal function and injury by inhibiting the NLRP3 pathway in HUA mice' kidneys. Additionally, BQ could alleviate ankle joint swelling and synovial injury, inhibit the TLR4/NLRP3 pathway, and reduce levels of inflammatory factors including interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) in AGA rats. The main component of BQ, brucine, could inhibit the activation of NLRP3/NF-κB pathway induced by MSU and reduce the expression level of inflammatory factors (IL-6, IL-1β, and TNF-α) in macrophages. Brucine could inhibit the activation of the EMT pathway and reduce the expression level of inflammatory factors (IL-6, TNF-α) in human fibroblast-like synoviocytes (MH7A cells) induced by MSU. ConclusionsBQ effectively reduced serum uric acid levels, improved kidney and joint damage, and ameliorated the inflammatory response caused by MSU. Its main component, brucine, effectively improved the inflammatory response and reduced the invasive ability of synoviocytes induced by MSU.

Uric acid and alterations of purine recycling disorders in Parkinson’s disease: a cross-sectional study

The relationship between reduced serum uric acid (UA) levels and Parkinson’s disease (PD), particularly purine metabolic pathways, is not fully understood. Our study compared serum and cerebrospinal fluid (CSF) levels of inosine, hypoxanthine, xanthine, and UA in PD patients and healthy controls. We analyzed 132 samples (serum, 45 PD, and 29 age- and sex-matched healthy controls; CSF, 39 PD, and 19 age- and sex-matched healthy controls) using liquid chromatography-tandem mass spectrometry. Results showed significantly lower serum and CSF UA levels in PD patients than in controls (p < 0.0001; effect size r = 0.5007 in serum, p = 0.0046; r = 0.3720 in CSF). Decreased serum hypoxanthine levels were observed (p = 0.0002; r = 0.4338) in PD patients compared to controls with decreased CSF inosine and hypoxanthine levels (p < 0.0001, r = 0.5396: p = 0.0276, r = 0.2893). A general linear model analysis indicated that the reduced UA levels were mainly due to external factors such as sex and weight in serum and age and weight in CSF unrelated to the purine metabolic pathway. Our findings highlight that decreased UA levels in PD are influenced by factors beyond purine metabolism, including external factors such as sex, weight, and age, emphasizing the need for further research into the underlying mechanisms and potential therapeutic approaches.

Effectiveness of a Single Fixed Dose of 3 mg Rasburicase for the Prevention and Management of Hyperuricemia in Tumor Lysis Syndrome in Adults With Cancer.

Tumor lysis syndrome (TLS) is a critical and potentially fatal complication linked to specific types of cancer. Rasburicase stands as a crucial medication necessary for the prevention and treatment of hyperuricemia, a condition commonly associated with TLS. Due to a shortage of rasburicase during the COVID-19 pandemic, a fixed-dose strategy of 3 mg rasburicase was used in many adult cancer patients in our center. The objective of this study was to assess the effectiveness of a fixed dose of 3 mg rasburicase in preventing and managing hyperuricemia associated with TLS in adult cancer patients. We conducted a retrospective, observational cohort study between March 2020 and February 2022. The study included adult patients who received a fixed dose of 3 mg rasburicase. The primary outcome measure was the reduction in serum uric acid (UA) levels at 24 and 48 hours after treatment, with the aim of achieving and maintaining normal UA levels. Seventeen patients in the treatment group and 20 patients in the prevention group were included. In the treatment group, 15 (88%) patients had normalization of serum UA, which is considered to be <7 mg/dL (median: 4.48 mg/dL) at 24 hours, and 16 (94%) patients had achieved normal UA at 48 hours (median: 2.78 mg/dL) after receiving the rasburicase dose. In the prevention group, all 20 (100%) patients achieved normal UA at 24 hours after receiving the rasburicase dose. Based on these findings, a single fixed dose of 3 mg rasburicase is effective for preventing and managing hyperuricemia associated with TLS in high-risk patients.

Uric Acid as a Biomarker for Mood Disorders: A Comparative Study of Blood Uric Acid Levels Correlating With the Symptom Severity and Treatment Response.

Background Bipolar affective disorder (BPAD) and major depressive disorder (MDD) are two mood disorders whose pathophysiology may involve the purinergic system. Elevated uric acid levels, associated with this system, can impact various behaviors in individuals affected by these conditions. In addition to genetic predisposition, blood uric acid levels can be impacted by various factors, including metabolic syndrome, the consumption of psychoactive medications, and other underlying kidney conditions such as gout. Objective The study aims to investigate the relationship between blood uric acid levels and mental health conditions, specifically BPAD subtypes (manic and depressive) and MDD. The study also examines changes in blood uric acid levels following treatment and evaluates the effectiveness of different treatment approaches in reducing uric acid levels. Methodology To be eligible to participate, individuals must have a confirmed diagnosis of BPAD (manic or depressive type) or MDD, according to the International Classification of Diseases (ICD-10). Blood uric acid levels were measured at both baseline and follow-up assessments. Symptoms were assessed weekly using standardized rating scales (Young Mania Rating Scale (YMRS) and Hamilton Rating Scale for Depression (HAM-D)) until treatment response was achieved, which was defined as a 50% reduction in initial scores on both scales. We used ANOVA to examine the differences among the three patient groups and paired sample t-tests to examine the changes in means before and after treatment conditions. Results A significant positive correlation was found between the severity of illness and serum uric acid levels across all three patient groups: those with BPAD-mania, BPAD-depression, and MDD. Notably, patients with BPAD-mania patients had significantly higher serum uric acid levels (5.2±0.9 mg/dL) compared to those with BPAD-depression (4.8±1.0 mg/dL) and MDD (4.0±1.1 mg/dL). After treatment, all patient groups exhibited a decrease in serum uric acid levels. The reduction in serum uric acid levels was pronounced in all patient groups, with decreases of 3.1±0.8 mg/dL in patients with BPAD-mania, 3.1±0.9 mg/dL in those with BPAD-depression, and 3.5±1.1 mg/dL in those with MDD. The study showed that the reduction in serum uric acid levels was significantly correlated with the severity of illness in patients with BPAD-mania, but not in those with BPAD-depression or MDD. Furthermore, the study found that treatment with lithium carbonate, sodium valproate, or carbamazepine was equally effective in reducing serum uric acid levels, regardless of the mood stabilizer used. Conclusion The study supports that dysfunction in the purine system might play a significant role in the development and progression of BPAD, suggesting that this phenomenon is not solely due to chronicity or medication exposure. This study also introduces a fresh perspective on the underlying biological processes that contribute to the development of BPAD and also sheds light on new treatment regimens targeting uric acid reduction in treating patients with bipolar disorder.

The SGLT2 inhibitor dapagliflozin ameliorates renal fibrosis in hyperuricemic nephropathy

Hyperuricemic nephropathy (HN) is a global metabolic disorder characterized by uric acid (UA) metabolism dysfunction, resulting in hyperuricemia (HUA) and tubulointerstitial fibrosis (TIF). Sodium-dependent glucose transporter 2 inhibitor, dapagliflozin, has shown potential in reducing serum UA levels in patients with chronic kidney disease (CKD), though its protective effects against HN remain uncertain. This study investigates the functional, pathological, and molecular changes in HN through histological, biochemical, and transcriptomic analyses in patients, HN mice, and UA-stimulated HK-2 cells. Findings indicate UA-induced tubular dysfunction and fibrotic activation, which dapagliflozin significantly mitigates. Transcriptomic analysis identifies estrogen-related receptor α (ERRα), a downregulated transcription factor in HN. ERRα knockin mice and ERRα-overexpressed HK-2 cells demonstrate UA resistance, while ERRα inhibition exacerbates UA effects. Dapagliflozin targets ERRα, activating the ERRα-organic anion transporter 1 (OAT1) axis to enhance UA excretion and reduce TIF. Furthermore, dapagliflozin ameliorates renal fibrosis in non-HN CKD models, underscoring the therapeutic significance of the ERRα-OAT1 axis in HN and CKD.

Research on cognitive impairment and potential risk factors in peritoneal dialysis patients: An observational study.

The objective of this study is to investigate the associated risk factors and their effects on cognitive impairment (CI) in patients undergoing peritoneal dialysis. A retrospective analysis was conducted on the basic information of 268 patients who underwent continuous ambulatory peritoneal dialysis (CAPD) at our hospital from January 2020 to September 2023. Cognitive function was assessed using the Montreal Cognitive Assessment Scale during their subsequent dialysis visits. Participants were categorized into a CI group and a cognitively normal group. Blood and other biological samples were collected for relevant biomarker analysis. Subsequently, we analyzed and compared the factors influencing CI between the 2 groups. The prevalence of CI among CAPD patients was 58.2%. Compared to the cognitively normal group, the CI group had a higher prevalence of alcohol consumption, lower levels of education, and reduced serum uric acid levels (P < .05). There was also a higher incidence of autoimmune diseases such as systemic lupus erythematosus in the CI group (P < .05). In terms of dialysis efficacy, the residual kidney Kt/V and residual kidney Ccr were significantly lower in the CI group compared to the cognitively normal group. In blood parameters, the CI group showed elevated total cholesterol levels and lower serum calcium concentrations (P < .05). Logistic regression analysis identified male gender, older age, lower educational attainment, hypercholesterolemia, and elevated high-sensitivity C-reactive protein levels as independent risk factors for CI in CAPD patients (P < .05). Additionally, in this patient cohort, dialysis duration and residual renal function were protective factors against CI (P < .05). CI is prevalent among PD patients. Elevated high-sensitivity C-reactive protein levels, male gender, older age, lower educational attainment, and hypercholesterolemia constitute an independent risk factor for CI in CAPD patients, whereas residual renal function acts as a protective element.

Assessment of oral toxicity of Moringa oleifera Lam aqueous extract and its effect on gout induced in a murine model.

Although widely employed in traditional remedies globally, the safety and efficacy of Moringa oleifera remain inadequately documented through scientific research. This study evaluated the oral toxicity of M. oleifera leaf aqueous extract (MoAE) and its impact on gout-induced rats. 2000 mg/kg was given in a single dose during the acute oral toxicity test, while 100 mg/kg, 250 mg/kg, and 500 mg/kg were given daily for 28 days in the repeated dose toxicity test. 100 mg/kg, 250 mg/kg, and 500 mg/kg MoAE doses were administered during the assessment of its impact on gout caused by monosodium urate. In the hyperuricemia model induced by oxonic acid, serum uric acid levels were assessed and pain response was measured through acetic acid-induced writhing. In acute oral and 28-day repeated dose tests, no indications of toxicity were detected, while MoAE alleviated ankle joint swelling and reduced serum uric acid concentrations in arthritic rats, causing a significant reduction in acetic acid-induced contortions. No acute oral toxicity or toxicity in 28-day repeated doses was found for MoAE, while it exhibited antiarthritic, antihyperuricemic, and pain-relieving effects in the murine model.

Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia

BACKGROUND Patients with chronic heart failure (CHF) frequently develop hyperuricemia, an elevated serum uric acid level, associated with adverse outcomes. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction (HFrEF), irrespective of diabetes. However, dapagliflozin’s effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear. AIM To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia. METHODS We conducted a randomized, double-blind, placebo-controlled trial in 200 patients with CHF and hyperuricemia, with HFrEF and serum uric acid levels ≥ 7 mg/dL (≥ 416 μmol/L). The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months. The primary endpoint was the change in serum uric acid level from baseline to 24 months. Secondary endpoints included changes in left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and quality of life (QoL) scores, as well as the incidence of cardiovascular death and hospitalization for heart failure. RESULTS At 24 months, dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL (71 μmol/L) compared with placebo (95%CI: -1.5 to -0.9; P &lt; 0.001). Dapagliflozin also significantly improved LVEF by 3.5% (95%CI: 2.1-4.9; P &lt; 0.001), NT-proBNP by 25% (95%CI: 18-32; P &lt; 0.001), and QoL scores by 10 points (95%CI: 7-13; P &lt; 0.001) and reduced the risk of cardiovascular death and hospitalization for heart failure by 35% (95%CI: 15–50; P = 0.002) compared with the placebo. Adverse events were similar between the two groups, except for a higher rate of genital infections in the dapagliflozin group (10% vs 2%, P = 0.01). CONCLUSION Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia. Therefore, dapagliflozin may be a useful therapeutic option for this high-risk population.

Simiao pills alleviates renal injury associated with hyperuricemia: A multi-omics analysis

Ethnopharmacological relevanceSimiao Pills, a classical traditional Chinese medicine prescription recorded in Cheng Fang Bian Du, has been traditionally used to treat hyperuricemia due to its heat-clearing and diuretic properties. Studies have shown that Simiao Pills effectively reduce uric acid levels. However, further research is needed to elucidate the precise composition of Simiao Pills for treating hyperuricemia and their potential pharmacological mechanism. Aim of the studyThis study aimed to investigate the therapeutic effects of Simiao Pills on hyperuricemia, with a particular focus on evaluating their protective role against hyperuricemia-induced renal injury and elucidating the underlying mechanism of action. Materials and methodsUPLC-MS/MS was used to identify the components of Simiao Pills. The hyperuricemia model mice were established by intraperitoneal injecting potassium oxonate (PO) and oral administrating hypoxanthine (HX). Network pharmacology, transcriptome, and metabolomics analyses were integrated to explore the mechanism of Simiao Pills in reducing uric acid and protecting the kidney. Mechanistic and functional studies were conducted to validate the potential mechanisms. ResultsSimiao Pills were found to contain 12 characteristic components. Treatment with Simiao Pills significantly reduced serum uric acid levels and ameliorated hyperuricemia-induced renal injury. Simiao Pills inhibited the enzymatic activities of XOD and XDH, and regulated the uric acid transporters in the kidney and ileum. Transcriptome and network pharmacology analyses highlighted quercetin, berberine, kaempferol, and baicalein as the principal active components of Simiao Pills acting on the kidney during hyperuricemia treatment, primarily impacting fibrosis, apoptosis, and inflammation-related signaling pathways. Metabolomic analysis unveiled 21 differential metabolites and 5 metabolic pathways associated with Simiao Pills against renal injury associated with hyperuricemia. Further experimental results validated that Simiao Pills reduced renal fibrosis, apoptotic renal cells, serum inflammation levels, and inhibited the NF-κB/NLRP3/IL-1β signaling pathway. ConclusionThis study demonstrated that Simiao Pills significantly reduced serum uric acid levels and improved renal injury by regulating inflammation, apoptosis, and renal fibrosis. These findings have provided a robust scientific pharmacological basis for the use of Simiao Pills in treating hyperuricemia patients.

Antigout effects and mechanisms of total flavonoids from prunus tomentosa.

In recent years, hyperuricemia and acute gouty arthritis have become increasingly common, posing a serious threat to public health. Current treatments primarily involve Western medicines with associated toxic side effects. This study aims to investigate the therapeutic effects of total flavones from Prunus tomentosa (PTTF) on a rat model of gout and explore the mechanism of PTTF's anti-gout action through the TLR4/NF-κB signaling pathway. We measured serum uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) levels using an enzyme-linked immunosorbent assay (ELISA). Histopathological changes were observed using HE staining, and the expression levels of relevant proteins were detected through Western blotting. After PTTF treatment, all indicators improved significantly. PTTF reduced blood levels of UA, Cr, BUN, IL-1β, IL-6, and TNF-α, and decreased ankle swelling. PTTF may have a therapeutic effect on animal models of hyperuricemia and acute gouty arthritis by reducing serum UA levels, improving ankle swelling, and inhibiting inflammation. The primary mechanism involves the regulation of the TLR4/NF-κB signaling pathway to alleviate inflammation. Further research is needed to explore deeper mechanisms.

#1116 Hyperuricemia worsens bacterial sepsis by suppressing neutrophil functions in CKD

Abstract Background and Aims Patients with kidney disease, especially those on dialysis, are more susceptible to infections such as peritonitis, sepsis, pneumonia, and are at a higher risk for infection-related mortality. Pathogenic mechanisms underlying the secondary immunodeficiency in kidney disease include gut dysbiosis and barrier dysfunction, persistent inflammation, immune paralysis due to increased levels of immunoregulatory metabolites (e.g. uric acid) and proteins (e.g. FGF23) [1]. Currently, it is unknown whether CKD-related hyperuricemia may contribute to the immune paralysis in this context. We hypothesized that hyperuricemia (HU) may aggravate the innate immune response to infection in CKD in mice. Method Mono- and polybacterial sepsis was induced by LPS injection or cecal ligation and puncture in Alb-creERT2;Glut9lox/lox mice with HU and/or CKD, and in Glut9lox/lox (healthy) control mice. After 24 hours, systemic inflammation was evaluated by measuring serum cytokine levels, immune cell activation and recruitment, and neutrophil extracellular trap release. Tissue injury in liver, heart, and kidney was assessed by performing RT-qPCR and immunohistochemistry. In addition, kidney function was determined by measuring the glomerular filtration rate (GFR). Additionally, mice were treated with urate-lowering therapy to reduce serum uric acid levels and the immune response and functional outcomes after sepsis is quantified. Results We found that both mono- and polybacterial sepsis caused systemic inflammation as indicated by an increased number of blood neutrophils (see Figure), neutrophil activation and pro-inflammatory cytokine levels as compared to the PBS-treated or sham-operated control groups in Glut9lox/lox healthy mice, respectively. Mice with sepsis also displayed a slightly worsened kidney function. Interestingly, HU significantly increased neutrophil numbers but decreased their activation status and the ability of neutrophils to form neutrophil extracellular traps in Alb-creERT2;Glut9lox/lox mice with sepsis as compared to the control groups, which was further aggravated in mice with CKD-related HU (CKD+HU). This impaired inflammatory response was partially reversible by lowering serum uric acid with febuxostat. Conclusion Our results identify hyperuricemia related or unrelated to kidney disease as immune regulator in bacterial infection by suppressing neutrophil functions in mice. Specifically targeting uric acid may help to overcome the secondary immunodeficiency related to kidney disease during infection but enhances sterile inflammation [2].