Management Of Hyperuricemia Research Articles

Asymptomatic hyperuricemia: to treat or not a threat? A clinical and evidence-based approach to the management of hyperuricemia in the context of cardiovascular diseases.

Asymptomatic hyperuricemia is defined by serum uric acid levels above 6.2 mg/dl in women and 7 mg/dl in men. In the presence of monosodium urate crystal formation and articular inflammation, hyperuricemia may become symptomatic (namely nephrolithiasis and gout). Uric acid results from purine catabolism and is at the centre of a complex metabolic interplay that involves oxidative stress, inflammation, renin-angiotensin-aldosterone system (RAAS) activation and insulin resistance. Uric acid levels present a continuous relation with conditions like hypertension and chronic kidney disease (CKD) and are reported to have an impact on risk of cardiovascular events. However, whether elevated uric acid is a causal agent and thus a possible therapeutic target is still uncertain and matter of further investigation. Treating symptomatic hyperuricemia involves lowering uric acid drugs and controlling inflammation. Urate-lowering agents are well tolerated but show minimal impact on cardiovascular events in patients with gout. Use of direct-acting urate-lowering agents in asymptomatic hyperuricemia associated with cardiovascular diseases does not warrant a clear benefit, whereas addressing cardiovascular issues with guideline-recommended therapies lowers uric acid and reduces the occurrence of cardiovascular events. Regular assessment of uric acid and clinical symptoms is advised before starting and renewing a urate-lowering treatment.

Unconjugated bilirubin promotes uric acid restoration by activating hepatic AMPK pathway

Hyperuricemia and its development to gout have reached epidemic proportions. Systemic hyperuricemia is facilitated by elevated activity of xanthine oxidase (XO), the sole source of uric acid in mammals. Here, we aim to investigate the role of bilirubin in maintaining circulating uric acid homeostasis. We observed serum bilirubin concentrations were inversely correlated with uric acid levels in humans with new-onset hyperuricemia and advanced gout in a clinical cohort consisting of 891 participants. We confirmed that bilirubin biosynthesis impairment recapitulated traits of hyperuricemia symptoms, exemplified by raised circulating uric acid levels and accumulated hepatic XO, and exacerbated mouse hyperuricemia development. Bilirubin administration significantly decreased circulating uric acid levels in hyperuricemia-inducing (HUA) mice receiving potassium oxonate (a uricase inhibitor) or fed with a high fructose diet. Finally, we proved that bilirubin ameliorated mouse hyperuricemia by increasing hepatic autophagy, restoring antioxidant defense and normalizing mitochondrial function in a manner dependent on AMPK pathway. Hepatocyte-specific AMPKα knockdown via adeno-associated virus (AAV) 8-TBG-mediated gene delivery compromised the efficacy of bilirubin in HUA mice. Our study demonstrates the deficiency of bilirubin in hyperuricemia progression, and the protective effects exerted by bilirubin against mouse hyperuricemia development, which may potentiate clinical management of hyperuricemia.

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.

Analysis of Blood Lipids, Blood Glucose, Blood Uric Acid, and Blood Routine Test Results in Retired Employees of a Unit in the Civil Aviation System

Objective: To investigate and analyze the annual physical examination results of retired employees from a unit in the civil aviation system, focusing on blood lipids, blood glucose, blood uric acid, and blood routine results. The study aims to provide relevant references for formulating reasonable disease management measures for preventing and controlling hyperlipidemia, hyperuricemia, and other conditions in retired employees. Methods: The examination results of 231 participants were collected and analyzed. The participants were divided into four groups based on age: middle-aged group, young-old group, middle-old group, and old-old group. The blood test results were compared across these groups, and an assessment of atherosclerotic cardiovascular disease (ASCVD) risk levels was completed in conjunction with medical history. Blood test results were also compared by gender. Results: There were no significant statistical differences in blood test results when grouped by age. However, the prevalence of hyperuricemia was higher in males than in females, while the prevalence of hypercholesterolemia was higher in females than in males. The LDL-C target achievement rate was lower in the moderate-and-high-risk group as well as the very high-risk group as defined by ASCVD risk levels. Conclusion: Management of hyperuricemia and hyperlipidemia in retired employees (elderly patients) should be strengthened to reduce the risk of ASCVD events and alleviate the potential medical burden associated with disease progression.

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.

Harnessing Protein Hydrolysates and Peptides for Hyperuricemia Management: Insights into Sources, Mechanisms, Techniques, and Future Directions.

Hyperuricemia (HUA) is a metabolic disorder characterized by an imbalance in uric acid production and excretion, frequently leading to gout and various chronic conditions. Novel bioactive compounds offer effective alternatives for managing HUA, reducing side effects of traditional medications. Recent studies have highlighted the therapeutic potential of protein hydrolysates and peptides in managing HUA. This review focuses on preparing and applying protein hydrolysates to treat HUA and explores peptides for xanthine oxidase inhibition. Particularly, we discuss their origins, enzymatic approaches, and mechanisms of action in detail. The review provides an updated understanding of HUA pathogenesis, current pharmacological interventions, and methodologies for the preparation, purification, identification, and assessment of these compounds. Furthermore, to explore the application of protein hydrolysates and peptides in the food industry, we also address challenges and propose solutions related to the safety, bitterness, oral delivery, and the integration of artificial intelligence in peptide discovery. Bridging traditional pharmacological approaches and innovative dietary interventions, this study paves the way for future research and development in HUA management, contributing to the utilization of proteins from different food sources. In conclusion, protein hydrolysates and peptides show significant promise as safe agents and dietary interventions for preventing and treating HUA.

Effects of hydrogen-rich water on blood uric acid in patients with hyperuricemia: A randomized placebo-controlled trial

BackgroundConsumption of hydrogen-rich water (HRW) has been shown to have anti-inflammatory and metabolic-modulatory benefits. ObjectiveA randomized, placebo-controlled trial was conducted to assess the potential blood uric acid-lowering effects of HRW consumption with different doses (low and high doses) and duration (4 and 8 weeks) in patients with hyperuricemia. MethodsThe Placebo group consumed three bottles of ordinary drinking water (330 mL per bottle), the Low-HRW group consumed two bottles of HRW (330 mL per bottle, H2 ≥ 4.66 mg/L) and a bottle of ordinary water, and the High-HRW group consumed three bottles of HRW daily for 8 weeks. The primary outcome was the blood uric acid levels following different time points (4 and 8 weeks) compared to baseline. ResultsA total of 100 participants completed the entire trial (32 in Placebo, 35 in Low-HRW, and 33 in High-HRW groups). The high-dose of HRW was more effective than low-dose HRW in controlling blood uric acid. Following an 8-week period, the High-HRW group exhibited a significant reduction in blood uric acid levels compared to the baseline (488.2 ± 54.1 μmol/L to 446.8 ± 57.1 μmol/L, P < 0.05). ConclusionAs a rather safe agent, the prolonged consumption of HRW may be feasible in the management of hyperuricemia. Clinical trial registrationchictr.org.cn, identifier ChiCTR2200066369.

Immunogenicity-masking delivery of uricase against hyperuricemia and gout

Improving the activity of uricase and lowering its immunogenicity remain significant challenges in the enzyme replacement management of hyperuricemia and related inflammatory diseases. Herein, an immunogenicity-masking strategy based on engineered red blood cells (RBCs) was developed for effective uricase delivery against both hyperuricemia and gout. The dynamic membrane of RBCs enabled high resistance to protease inactivation and hydrogen peroxide accumulation. Benefiting from these advantages, a single infusion of RBC-loaded uricase (Uri@RBC) performed prolonged blood circulation and sustained hyperuricemia management. Importantly, RBCs masked the immunogenicity of uricase, leading to the maintenance of UA-lowering performance after repeated infusion through reduced antibody-mediated macrophage clearance. In an acute gout model, Uri@RBC profoundly alleviated joint edema and inflammation with minimal systemic toxicity. This study supports the employment of immunogenicity-masking tools for efficient and safe enzyme delivery, and this strategy may be leveraged to improve the usefulness of enzyme replacement therapies for managing a wide range of inflammatory diseases.

Quercetin as the primary xanthine oxidase inhibitor compound in Maclura tricuspidata leaf

Maclura tricuspidata (MT) leaf demonstrated various health benefits, notably the inhibition of xanthine oxidase (XOD) activity, which is crucial in the management of hyperuricaemia and many diseases related to oxidative stress. This study aimed to identify the primary compound responsible for this inhibitory effect. Through a systematic investigation, MT leaf extracts were subjected to solvent-solvent partitioning using ethyl acetate, n-hexane, n-butanol, and dichloromethane. Further purification involved adsorption and desorption using Amberlite XAD-2 resin, followed by column chromatography on Silica Gel and Sephadex LH-20. The purified compounds were analysed using UPLC-QTOF-MS coupled with NMR spectroscopy. Our findings identified quercetin, a phenolic compound, as the most significant inhibitor of XOD activity in MT leaf, with an IC50 value of 212.92 μg/ml. This is the first report of purifying and identifying a single compound responsible for XOD inhibition in MT.

Hyperuricemia - consequences of not initiating therapy. Benefits and drawbacks of treatment.

Hyperuricemia, characterized by elevated levels of uric acid in the body, is associated with several health risks, including gout, urolithiasis and cardiovascular disease. Although treatment options are available, they can lead to hypersensitivity reactions, particularly with allopurinol therapy. This paper provides a comprehensive review of the consequences of hyperuricemia, the need for treatment and the potential adverse effects of allopurinol, illustrated by a case study. The study highlights the importance of careful consideration before initiating therapy, particularly in patients with comorbidities and concomitant medication. It emphasizes the need for vigilant monitoring and individualized treatment approaches to reduce adverse effects. In addition, genetic factors, particularly HLA-B*5801, play an important role in determining susceptibility to allopurinol hypersensitivity reactions. This paper highlights the importance of informed decision making in the management of hyperuricemia to optimize patient outcomes while minimizing the risks associated with treatment.

Identification of aurones and chalcones as the main contributors to xanthine oxidase inhibitory activity of snow chrysanthemum

Snow chrysanthemum, the capitulum of Coreopsis tinctoria Nutt., was found to possess inhibitory activity on xanthine oxidase (XO), one of the key enzymes in the pathogenesis of gout. Assisted by bioactivity-oriented isolation, a total of 16 compounds containing a new compound were obtained from the active fractions of snow chrysanthemum extract, including two aurones (1, 2), four chalcones (3–6), a flavone (7), four flavonols (8-11), a flavanonol (12), three phenylpropanoids (13–15), and a new polyacetylene glycoside (16). All the isolated compounds were assayed for their inhibitory activity on XO, among which eight polyphenols (1–8) exhibited potent or moderate inhibitory activities with IC50 values from 0.65 to 29.11 μM. The structure-activity relationship was interpreted for polyphenols (1-12). Besides, the inhibition properties of compounds 1–4 against XO were comprehensively investigated through enzyme kinetics, fluorescence quenching, and docking simulation. Maritimetin (1) and sulfurein (2) reversibly inhibited XO by mixed type mechanism. Okanin-4′-O-(6″-acetyl)-β-d-glucopyranoside (3) and coreopsin (4) competitively inhibited XO in reversible and irreversible manners, respectively. In addition, fluorescence quenching studies suggested that all four compounds interacted with XO through a static quenching mechanism. Molecular docking inferred that hydrogen bonds and hydrophobic interaction played key roles in the binding process. This study revealed the XO-inhibitory activity of snow chrysanthemum and the contribution of containing aurones and chalcones to XO inhibition, making it a potential functional food ingredient for management of hyperuricemia.

Herbal remedies in the management of hyperuricemia and gout: A review of in vitro, in vivo and clinical evidences.

Gout, or hyperuricemia is a multifactorial and multi-faceted metabolic disease that is quite difficult to manage and/or treat. Conventional therapies such as non-steroidal anti-inflammatory drugs (NSAIDs) such as allopurinol, corticosteroids and colchicine amongst others, have helped in its management and treatment to some extent. This study aimed to compile and analyze the different herbal remedies used in the management of hyperuricemia and gout. A literature search was conducted from key databases (PubMed, ScienceDirect, Cochrane Library, Google Scholar) using relevant keywords via the PRISMA model. Smilax riparia A.DC. from Traditional Chinese Medicine is used in many countries for its therapeutic effect on lowering serum urate levels. No single study was able to establish the efficacy of a specific traditionally used herb via in vitro, in vivo, and clinical studies. Patients were found to use a panoply of natural remedies, mainly plants to treat hyperuricemia and gout, which have been validated to some extent by in vitro, in vivo, and clinical studies. Nonetheless, further research is needed to better understand the ethnopharmacological relationship of such herbal remedies.

Discovery of digallic acid as XOD/URAT1 dual target inhibitor for the treatment of hyperuricemia

The development of XOD/URAT1 dual target inhibitors has emerged as a promising therapeutic strategy for the management of hyperuricemia. Here, through virtual screening, we have identified digallic acid as a novel dual target inhibitor of XOD/URAT1 and subsequently evaluated its pharmacological properties, pharmacokinetics, and toxicities. Digallic acid inhibited URAT1 with an IC50 of 5.34 ± 0.65 μM, which is less potent than benzbromarone (2.01 ± 0.36 μM) but more potent than lesinurad (10.36 ± 1.23 μM). Docking and mutation analysis indicated that residues S35, F241 and R477 of URAT1 confer a high affinity for digallic acid. Digallic acid inhibited XOD with an IC50 of 1.04 ± 0.23 μM. Its metabolic product, gallic acid, inhibited XOD with an IC50 of 0.91 ± 0.14 μM. Enzyme kinetic studies indicated that both digallic acid and gallic acid act as mixed-type XOD inhibitors. It shares the same binding mode as digallic acid, and residues E802, R880, F914, T1010, N768 and F1009 contribute to their high affinity. The anion group (carboxyl) of digallic acid contribute significantly to its inhibition activity on both XOD and URAT1 as indicated by docking analysis. Remarkably, at a dosage of 10 mg/kg in vivo, digallic acid exhibited a stronger urate-lowering and uricosuric effect compared to the positive drug benzbromarone and lesinurad. Pharmacokinetic study indicated that digallic acid can be hydrolyzed into gallic acid in vivo and has a t1/2 of 0.77 ± 0.10 h. Further toxicity evaluation indicated that digallic acid exhibited no obvious renal toxicity, as reflected by CCK-8, biochemical analysis (CR and BUN) and HE examination. The findings of our study can provide valuable insights for the development of XOD/URAT1 dual target inhibitors, and digallic acid deserves further investigation as a potential anti-hyperuricemic drug.

Investigating the underlying mechanisms of Wuling powder in the management of hyperuricemia based on network pharmacology and molecular docking

Investigating the underlying mechanisms of Wuling powder in the management of hyperuricemia based on network pharmacology and molecular docking

THE MULTIFUNCTIONAL ROLE OF HERBAL PRODUCTS IN THE MANAGEMENT OF GOUT (VATARAKTA): A COMPREHENSIVE REVIEW

Introduction: Vatarakta is a Vata Vyadhi that occurs due to exacerbated Vata and Rakta Dosha by their causa-tive factors. It can occur in the whole body but since joints of the hand and foot are more affected it resembles gouty arthritis as described in allopathic science. Gout is a disease described in conventional medicine that has similarities to the Vatarakta. It is a type of inflammatory arthritis that is triggered by the crystallization of uric acid within the joints and is often associated with hyperuricemia. Hyperuricemia can be caused by overproduc-tion of uric acid, or, more commonly by inefficient excretion by the kidneys. The clinical presentation of gout ranges from the typical episodic acute inflammation of the joint to chronic tophaceous gout, chronic polyarticular arthritis, urate nephrolithiasis, and interstitial nephropathies. Several herbal drugs are well known for their thera-peutic effects and lower toxicity and are important substances for new drug development. Objective: The objective of this systematic review was to explore and validate the efficacy of herbal medicines in the management of gout. This review aims to update some research findings regarding the biological activities of the herbal ingredients of Ayurvedic medicines used in gout and also to collect an adequate basis for the opti-mal integration of Ayurvedic medicines into the conventional health system (Allopath). Materials &amp; Methods: Systematic literature searches were carried out and the available information on Vatarak-ta and gout was collected via electronic search and a library search for articles published in peer-reviewed jour-nals and locally available books. Literature searches were also carried out to find the biochemical effects of vari-ous herbs mentioned in the management of hyperuricemia and gout. Conclusion: It has been demonstrated that plant-derived biochemicals have a potential effect on gout. These ef-fects comprise XOD inhibitory action, uricosuric, anti-inflammatory, anti-oxidant effects, etc. During the analy-sis of the literature available in Ayurveda, Allopathy, and related other branches of health science it was found that integrative medicine would be the optimal strategy to develop more effective agents in the treatment of gout (Vatarakta) and a combination of therapies may be very effective in reducing both the effect and frequency of disease.

Estimation of the spatial pattern of gout prevalence across China by wastewater-based epidemiology

Gout is a metabolic arthritis caused by hyperuricemia. In recent years, the prevalence of gout has been increased significantly in China due to the improvement of the living standards, and gout has become another common metabolic disease following diabetes mellitus. Gout severely affects the health status and life quality of human. In order to monitor the near real-time prevalence of gout, a wastewater-based epidemiology (WBE) approach was carried out in 257 Chinese cities using febuxostat as the biomarker. Febuxostat in wastewater was measured by a LC-MS/MS method with satisfactory results of method validation. The average concentration of febuxostat in wastewater was 53.05 ± 31.76 ng/L, with the estimated per capita consumption of 124.40 ± 73.37 mg/day/1000 inhabitant. The calculated prevalence of febuxostat was 0.41 % ± 0.24 %, and the prevalence of gout was finally estimated to be 1.30 % ± 0.77 % (0.60 % to 2.11 %), which was nearly consistent with value of 1.10 % obtained from the Guideline for the diagnosis and management of hyperuricemia and gout in China (2019). The results indicated that the febuxostat-based WBE approach might be reasonable to assess the near real-time gout prevalence in China.

Evaluation of purine-nucleoside degrading ability and in vivo uric acid lowering of Streptococcus thermophilus IDCC 2201, a novel antiuricemia strain.

This study evaluated 15 lactic acid bacteria with a focus on their ability to degrade inosine and hypo-xanthine-which are the intermediates in purine metabolism-for the management of hyperuricemia and gout. After a preliminary screening based on HPLC, Lactiplantibacillus plantarum CR1 and Lactiplantibacillus pentosus GZ1 were found to have the highest nucleoside degrading rates, and they were therefore selected for further characterization. S. thermophilus IDCC 2201, which possessed the hpt gene encoding hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and exhibited purine degradation, was also selected for further characterization. These three selected strains were examined in terms of their probiotic effect on lowering serum uric acid in a Sprague-Dawley (SD) rat model of potassium oxonate (PO)-induced hyperuricemia. Among these three strains, the level of serum uric acid was most reduced by S. thermophilus IDCC 2201 (p < 0.05). Further, analysis of the microbiome showed that administration of S. thermophlilus IDCC 2201 led to a significant difference in gut microbiota composition compared to that in the group administered with PO-induced hyperuricemia. Moreover, intestinal short-chain fatty acids (SCFAs) were found to be significantly increased. Altogether, the results of this work indicate that S. thermophilus IDCC 2201 lowers uric acid levels by degrading purine-nucleosides and also restores intestinal flora and SCFAs, ultimately suggesting that S. thermophilus IDCC 2201 is a promising candidate for use as an adjuvant treatment in patients with hyperuricemia.

Heterocyclic compounds as xanthine oxidase inhibitors for the management of hyperuricemia: synthetic strategies, structure-activity relationship and molecular docking studies (2018-2024).

Hyperuricemia is characterized by higher-than-normal levels of uric acid in the bloodstream. This condition can increase the likelihood of developing gout, a form of arthritis triggered by the deposition of urate crystals in the joints, leading to inflammation and pain. An essential part of purine metabolism is played by the enzyme xanthine oxidase (XO), which transforms xanthine and hypoxanthine into uric acid. Despite its vital role, diseases such as gout have been associated with elevated uric acid levels, which are linked to increased XO activity. To manage hyperuricemia, this study focuses on potential nitrogen based heterocyclic compounds that may serve as XO inhibitors which may lower uric acid levels and prevent hyperuricemia. Xanthine oxidase inhibitors are a class of medications used to treat conditions like gout by reducing the production of uric acid. The present study demonstrates numerous compounds, particularly nitrogen containing heterocyclic compounds including their synthesis, structure-activity relationship, and molecular docking studies. This paper also contains drugs undergoing clinical studies and the xanthine oxidase inhibitors that have been approved by the FDA.

Core-shell structured microneedles with programmed drug release functions for prolonged hyperuricemia management.

An appropriate non-oral platform via transdermal delivery of drugs is highly recommended for the treatment of hyperuricemia. Herein, a core-shell structured microneedle patch with programmed drug release functions was designed to regulate serum uric acid (SUA) levels for prolonged hyperuricemia management. The patch was fabricated using a three-step casting method. Allopurinol (AP), an anti-hyperuricemic drug, was encapsulated within the carboxymethyl cellulose (CMC) layer, forming the "shell" of the MNs. The MN's inner core was composed of polyvinylpyrrolidone (PVP) loaded with urate oxidase-calcium peroxide nanoparticles (UOx-CaO2 NPs). When the as-fabricated core-shell structured microneedles were inserted into the skin, the loaded AP was first released immediately to effectively inhibit the production of SUA due to the water solubility of CMC. Subsequently, the internal SUA was further metabolized by UOx, leading to exposure of CaO2 NPs. The sustained release of UOx accompanied by the decomposition of CaO2 NPs contributed to maintaining a state of normal uric acid levels over an extended period. More attractively, uric acid could be oxidized due to the strong oxidant of CaO2, which was beneficial to the continuous consumption of uric acid. In vivo results showed that the as-fabricated MNs exhibited an excellent anti-hyperuricemia effect to reduce SUA levels to the normal state within 3 h and maintain the normouricemia state for 12 h. In addition, the levels of creatinine (Cr) and blood urea nitrogen (BUN) in the serum remained within the normal range, and the activities of adenosine deaminase (ADA) and xanthine oxidase (XOD) in the liver were effectively inhabited, mitigating the risk of liver and kidney damage for clinical anti-hyperuricemia management.

Navigating the choice between topiroxostat and febuxostat for hyperuricemia management: A prospective comparative study

Navigating the choice between topiroxostat and febuxostat for hyperuricemia management: A prospective comparative study