Empowering probiotics with high xanthine transport for effective hyperuricemia management.

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.

A systematic review of single nucleotide polymorphisms affecting allopurinol pharmacokinetics and serum uric acid level.

Aim: To summarize the effects of single nucleotide polymorphisms (SNPs) on the pharmacokinetics of allopurinol to control uric acid levels.Methods: A comprehensive search was conducted in PubMed, Web of Science and Scopus databases from inception to January 2024, includes 17 articles focusing on SNPs and pharmacokinetics of allopurinol and oxypurinol.Results: A total of 11 SNPs showed a significant association with pharmacokinetics of allopurinol and oxypurinol, as well as their potential clinical implications.Conclusion: SNPs in ATP-binding cassette super-family G member 2 (ABCG2), solute carrier family 2 member 9 (SLC2A9), solute carrier family 17 member 1 (SLC17A1), solute carrier family 22 member 12 (SLC22A12), solute carrier family 22 member 13 (SLC22A13) and PDZ domain containing 1 (PDZK1) genes were associated with allopurinol clearance, while SNPs in aldehyde oxidase 1 (AOX1) genes involved in metabolism of allopurinol. SNPs in gremlin 2, DAN family BMP antagonist (GREM2) gene impacted uric acid control, but the specific mechanism governing the expression of GREM2 remains unknown. Our study indicated that the identified SNPs show contradictory effects, reflecting inconsistencies and differences observed across various studies.

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Exercise and hyperuricemia: an opinion article.

Hyperuricaemia (HUA) is an abnormally high concentration of serum urate caused by either an excess of uric acid production or decreased excretion capacity in the body. Serum urate concentration forms sodium salts that deposit in the soft tissues of the joints, ultimately leading to gout. Additionally, HUA is strongly associated with several acute and chronic illnesses. In various clinical guidelines and practices, xanthine oxidase inhibitors, such as allopurinol and febuxostat, are commonly used as the initial medication for treating HUA. However, extended usage of urate-lowering drugs may have risks, including cardiovascular thrombotic events and hepatic impairment. Implementing a scientifically informed fitness diet in conjunction with appropriate exercise may decrease HUA. Unfortunately, there is currently a shortfall in exercise intervention trials for individuals suffering from HUA. Most of the previous evidence suggesting that exercise improves serum urate levels comes from intervention trials in other populations, and serum urate is only one of the outcomes observed. This opinion article analyses the causes of HUA, offers dietary and exercise guidance with the aim of furnishing a point of reference for individuals with HUA or fitness enthusiasts.

Allopurinol versus Trimetazidine for the Treatment of Angina: A Randomized Clinical Trial. / Alopurinol Versus Trimetazidina para o Tratamento da Angina: Ensaio Clínico Randomizado.

BACKGROUND: Recently, it was demonstrated that allopurinol, a xanthine oxidase inhibitor, has cardiovascular and anti-ischaemic properties and may be a metabolic antianginal agent option.Objective: The objective of this study was to evaluate the antianginal effect of allopurinol as a third drug for patients with stable coronary artery disease (CAD). METHODS: This was a randomized clinical trial between 2018 and 2020 including patients with CAD who maintained angina despite initial optimization with beta-blockers and calcium channel blockers. The individuals were randomized 1:1 to 300 mg of allopurinol twice daily or 35 mg of trimetazidine twice daily. The main outcome was the difference in the angina frequency domain of the Seattle Angina Questionnaire (SAQ-AF). A probability (p) value < 0.05 was considered statistically significant. RESULTS: A hundred and eight patients were included in the randomization phase, with 54 (50%) in the allopurinol group and 54 (50%) in the trimetazidine group. Six (5.6%) individuals, 3 from each group, were lost to follow-up for the primary outcome. In the allopurinol and trimetazidine groups, the median SAQ-AF scores were 50 (30.0 to 70.0) and 50 (21.3 to 78.3), respectively. In both groups, the SAQ-AF score improved, but the median of the difference compared to baseline was lower in the allopurinol group (10 [0 to 30] versus 20 [10 to 40]; p < 0.001), as was the mean of the difference in the total SAQ score (12.8 ± 17.8 versus 21.2 ± 15.9; p = 0.014). CONCLUSION: Both allopurinol and trimetazidine improved the control of angina symptoms; however, trimetazidine presented a greater gain compared to baseline. Brazilian Registry of Clinical Trials - Registration Number RBR-5kh98y.

FUNDAMENTO: Recentemente, foi demonstrado que o alopurinol, um inibidor da xantina oxidase, possui propriedades cardiovasculares e anti-isquêmicas e pode ser uma opção de agente antianginoso metabólico. OBJETIVO: O objetivo do presente estudo foi avaliar o efeito antianginoso do alopurinol como terceiro medicamento para pacientes com doença arterial coronariana (DAC) estável. MÉTODOS: Trata-se de um ensaio clínico randomizado entre 2018 e 2020 incluindo pacientes com DAC que mantiveram angina apesar da otimização inicial com betabloqueadores e bloqueadores dos canais de cálcio. Os indivíduos foram randomizados 1:1 para 300 mg de alopurinol 2 vezes ao dia ou 35 mg de trimetazidina 2 vezes ao dia. O desfecho principal foi a diferença no domínio da frequência da angina do Questionário de Angina de Seattle (QAS-FA). Foram considerados estatisticamente significativos valores de probabilidade (p) < 0,05. RESULTADOS: Foram incluídos 108 pacientes na fase de randomização, com 54 (50%) no grupo alopurinol e 54 (50%) no grupo trimetazidina. Seis (5,6%) indivíduos, 3 de cada grupo, foram perdidos no seguimento para o desfecho primário. Nos grupos de alopurinol e trimetazidina, as pontuações medianas do QAS-FA foram 50 (30,0 a 70,0) e 50 (21,3 a 78,3), respectivamente. Em ambos os grupos, a pontuação do QAS-FA melhorou, mas a mediana da diferença em relação à linha de base foi menor no grupo alopurinol (10 [0 a 30] versus 20 [10 a 40]; p < 0,001), assim como a média da diferença na pontuação total do QAS (12,8 ± 17,8 versus 21,2 ± 15,9; p = 0,014). CONCLUSÃO: Tanto o alopurinol quanto a trimetazidina melhoraram o controle dos sintomas de angina; no entanto, a trimetazidina apresentou um ganho maior em relação à linha de base. Registro Brasileiro de Ensaios Clínicos ­ Número de Registro RBR-5kh98y.

Tumour lysis syndrome.

Tumour lysis syndrome (TLS) represents a critical oncological emergency characterized by extensive tumour cell breakdown, leading to the swift release of intracellular contents into the systemic circulation, outpacing homeostatic mechanisms. This process results in hyperuricaemia (a by-product of intracellular DNA release), hyperkalaemia, hyperphosphataemia, hypocalcaemia and the accumulation of xanthine. These electrolyte and metabolic imbalances pose a significant risk of acute kidney injury, cardiac arrhythmias, seizures, multiorgan failure and, rarely, death. While TLS can occur spontaneously, it usually arises shortly after the initiation of effective treatment, particularly in patients with a large cancer cell mass (defined as ≥500 g or ≥300 g/m2 of body surface area in children). To prevent TLS, close monitoring and hydration to improve renal perfusion and urine output and to minimize uric acid or calcium phosphate precipitation in renal tubules are essential. Intervention is based on the risk of a patient of having TLS and can include rasburicase and allopurinol. Xanthine, typically enzymatically converted to uric acid, can accumulate when xanthine oxidases, such as allopurinol, are administered during TLS management. Whether measurement of xanthine is clinically useful to optimize the use of allopurinol or rasburicase remains to be determined.

Urate lowering therapy in patients starting hemodialysis limit gout flares occurrence: ten years retrospective study.

BACKGROUND: Uncontrolled gout can cause articular impairment but is also associated with a global and cardiovascular excess mortality, especially in dialysis population. Data documented within existing research is not conclusive regarding gout flares evolution during hemodialysis and their control by urate lowering therapy (ULT). Without clear guidelines concerning hemodialysis patients management with chronic gout, this study proposes to investigate whether gout flare incidence reduction could be observed on this population treated by urate lowering therapy versus patients without treatment. METHODS: We performed a retrospective cohort study in two hemodialysis centers in France. Were selected patients over 18 years old with a gout history who started hemodialysis between January 2005 and September 2015. Demographics and clinicals data were recorded at hemodialysis start and throughout 5 years of follow up. Gout flare was defined as presence of uric acid crystal in joint punction or clinically diagnosed as such with a colchicine prescription. All statistical analysis were performed in SAS® version 9.4 (SAS Institute Inc., Cary, NC). RESULTS: One hundred eighty-one patients have been included, mean age at dialysis initiation was 68.6 years (± 12.4) with 72% of men, 54% were treated by ULT: 89.7% by allopurinol and 9.3% by febuxostat. One patient received both treatments successively. After hemodialysis initiation, 35.36% patients had experienced at least one gout flare. The appearance of at least one gout flare concerned 50% of patients in no ULT group and 22.68% patients in ULT group (p = 0.0002). Dialysis efficiency was measured at regular interval during follow-up and was similar in both groups. To study the association strength between clinical factors and gout flares occurrences, a Cox model was performed; ULT is a protector factor of gout flare (HR:0,42, CI 95: 0,25-0,71). The proportion of serum urate values within the target (median 53% vs 29.3%, p < 0.0001) was significantly higher in ULT group versus no ULT group (median 53% vs 29.3%, p < 0.0001). CONCLUSION: Urate lowering therapy limit new gout flares occurrence in hemodialysis patients with gout historyCollaboration between rheumatologists and nephrologists may help to update guidelines for urate-lowering therapies in patients on dialysis.

Easing the way to achieving target serum urate in people with gout: protocol for a non-inferiority randomised strategy trial using an allopurinol dosing model in Aotearoa/New Zealand (the Easy-Allo Study).

INTRODUCTION: Gout is one of the most common forms of arthritis worldwide. Gout is particularly prevalent in Aotearoa/New Zealand and is estimated to affect 13.1% of Maori men, 22.9% of Pacific men and 7.4% of New Zealand European men. Effective long-term treatment requires lowering serum urate to <0.36 mmol/L. Allopurinol is the most commonly used urate-lowering medication worldwide. Despite its efficacy and safety, the allopurinol dose escalation treat-to-target serum urate strategy is difficult to implement and there are important inequities in allopurinol prescribing in Aotearoa. The escalation strategy is labour intensive, time consuming and costly for people with gout and the healthcare system. An easy and effective way to dose-escalate allopurinol is required, especially as gout disproportionately affects working-age Maori men and Pacific men, who frequently do not receive optimal care. METHODS AND ANALYSIS: A 12-month non-inferiority randomised controlled trial in people with gout who have a serum urate ≥ 0.36 mmol/l will be undertaken. 380 participants recruited from primary and secondary care will be randomised to one of the two allopurinol dosing strategies: intensive nurse-led treat-to-target serum urate dosing (intensive treat-to-target) or protocol-driven dose escalation based on dose predicted by an allopurinol dosing model (Easy-Allo). The primary endpoint will be the proportion of participants who achieve target serum urate (<0.36 mmol/L) at 12 months. ETHICS AND DISSEMINATION: The New Zealand Northern B Health and Disability Ethics Committee approved the study (2022 FULL 13478). Results will be disseminated in peer-reviewed journals and to participants. TRIAL REGISTRATION NUMBER: ACTRN12622001279718p.

Verinurad Plus Allopurinol for Heart Failure With Preserved Ejection Fraction: The AMETHYST Randomized Clinical Trial.

Importance: Elevated serum uric acid (SUA) level may contribute to endothelial dysfunction; therefore, SUA is an attractive target for heart failure with preserved ejection fraction (HFpEF). However, to the authors' knowledge, no prior randomized clinical trials have evaluated SUA lowering in HFpEF. Objective: To investigate the efficacy and safety of the novel urate transporter-1 inhibitor, verinurad, in patients with HFpEF and elevated SUA level. Design, Setting, and Participants: This was a phase 2, double-blind, randomized clinical trial (32-week duration) conducted from May 2020 to April 2022. The study took place at 59 centers in 12 countries and included patients 40 years and older with HFpEF and SUA level greater than 6 mg/dL. Data were analyzed from August 2022 to May 2024. Interventions: Eligible patients were randomized 1:1:1 to once-daily, oral verinurad, 12 mg, plus allopurinol, 300 mg; allopurinol, 300 mg, monotherapy; or placebo for 24 weeks after an 8-week titration period. Allopurinol was combined with verinurad to prevent verinurad-induced urate nephropathy, and the allopurinol monotherapy group was included to account for allopurinol effects in the combination therapy group. All patients received oral colchicine, 0.5 to 0.6 mg, daily for the first 12 weeks after randomization. Main Outcomes and Measures: Key end points included changes from baseline to week 32 in peak oxygen uptake (VO2), Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS), and SUA level; and safety/tolerability (including adjudicated cardiovascular events). Results: Among 159 randomized patients (53 per treatment group; median [IQR] age, 71 [40-86] years; 103 male [65%]) with median (IQR) N-terminal pro-brain natriuretic peptide level of 527 (239-1044) pg/mL and SUA level of 7.5 (6.6-8.4) mg/dL, verinurad plus allopurinol (mean change, -59.6%; 95% CI, -64.4% to -54.2%) lowered SUA level to a greater extent than allopurinol (mean change, -37.6%; 95% CI, -45.3% to -28.9%) or placebo (mean change, 0.8%; 95% CI, -11.8% to 15.2%; P < .001). Changes in peak VO2 (verinurad plus allopurinol, 0.27 mL/kg/min; 95% CI, -0.56 to 1.10 mL/kg/min; allopurinol, -0.17 mL/kg/min; 95% CI, -1.03 to 0.69 mL/kg/min; placebo, 0.37 mL/kg/min; 95% CI, -0.45 to 1.19 mL/kg/min) and KCCQ-TSS (verinurad plus allopurinol, 4.3; 95% CI, 0.3-8.3; allopurinol, 4.5; 95% CI, 0.3-8.6; placebo, 1.2; 95% CI, -3.0 to 5.3) were similar across groups. There were no adverse safety signals. Deaths or cardiovascular events occurred in 3 patients (5.7%) in the verinurad plus allopurinol group, 8 patients (15.1%) in the allopurinol monotherapy group, and 6 patients (11.3%) in the placebo group. Conclusions and Relevance: Results of this randomized clinical trial show that despite substantial SUA lowering, verinurad plus allopurinol did not result in a significant improvement in peak VO2 or symptoms compared with allopurinol monotherapy or placebo in HFpEF. Trial Registration: ClinicalTrials.gov Identifier: NCT04327024.

Use of allopurinol to manage skewed 6-mercaptopurine metabolism in pediatric maintenance acute lymphoblastic leukemia treatment.

BACKGROUND: 6-mercaptopurine is a cornerstone of maintenance therapy for pediatric ALL. Response to 6MP is typically determined by the ANC. Therapeutic ANC range while receiving 6MP is between 500 and 1500/µL. In addition to desired myelosuppression, 6MP is associated with multiple adverse drug effects. Increased doses of 6MP can lead to therapeutic ANC values; however, patients may experience adverse effects before obtaining therapeutic myelosuppression, often deemed "skewed metabolism." Allopurinol may potentially correct skewed 6MP metabolism. PROCEDURE: Pediatric patients with ALL with 6MMP and 6TGN metabolites drawn during maintenance therapy were analyzed for allopurinol use. The primary outcome evaluated the percentage of time spent in therapeutic ANC range before and after allopurinol initiation. In addition, the difference in 6MMP:6TGN ratios before and after allopurinol initiation, incidence of hepatotoxicity, and rates of relapse, were analyzed. RESULTS: Ninety-five patients were included for analysis. Thirty-two (34%) patients received allopurinol. There were no significant differences in baseline demographics between the patients who received allopurinol and those who did not. When comparing ANC values pre- and post-allopurinol initiation, a statistically significant increase in the percentage of time spent in therapeutic range was observed (27% vs. 43%; p = .03). In addition, when comparing metabolite ratios pre- and post-allopurinol initiation, a statistically significant decrease in 6MMP:6TGN metabolite ratio values was observed (86.7 vs. 3.6; p < .0001). CONCLUSIONS: Allopurinol significantly increased the percent time in therapeutic ANC range and can be safely utilized to significantly lower the ratio of 6MMP:6TGN metabolites, alleviating the undesirable side effects of 6MMP, and optimizing the anti-leukemic effects associated with 6TGN.

Randomised, double-blind, placebo-controlled study evaluating the effect of allopurinol on the risk of cardiovascular events in patients with high and very high cardiovascular risk, including the presence of long-COVID-19 syndrome: the ALL-VASCOR study protocol.

INTRODUCTION: Numerous studies, but not all, have suggested a positive effect of allopurinol on the cardiovascular system. The randomised, double-blind, placebo-controlled study evaluating the effect of allopurinol on the risk of cardiovascular events in patients with high and very high cardiovascular risk, including the presence of long-COVID-19 syndrome (ALL-VASCOR) study aims to evaluate the efficacy of allopurinol therapy for improving cardiovascular outcomes in patients at high and very high cardiovascular risk excluding ischaemic heart disease. This is particularly important due to the high cost of cardiovascular disease treatment and its status as one of the leading causes of mortality. METHODS AND ANALYSIS: The ALL-VASCOR study is a randomised, double-blind, placebo-controlled, multicentre trial that examines the effect of allopurinol therapy (200-500 mg of allopurinol daily) versus an equivalent dose of placebo on the risk of cardiovascular events in 1116 patients aged 40-70 with serum uric acid levels above 5 mg/dL at high and very high risk of cardiovascular disease. The ALL-VASCOR study will also assess the occurrence of long-COVID-19 syndrome. The study will measure primary and secondary as well as additional endpoints and the planned intervention will end on 31 July 2028 unless advised otherwise by the Safe Monitoring Board or other applicable authorities. Participant recruitment is planned to begin in March 2024 in Poland. ETHICS AND DISSEMINATION: The study was ethically approved by the Bioethics Committee of Poznan University of Medical Sciences (No 03/23, 12 January 2023). The results are expected after 2028 and will be disseminated in peer-reviewed journals and at international conferences. PROTOCOL VERSION NUMBER: 01-15 November 2022. TRIAL REGISTRATION NUMBER: EudraCT: 2022-003573-32, 27 October 2022, ClinicalTrials: NCT05943821, 13 July 2023.

ALLOPURINOL TREATMENT IMPROVES INSULIN RESISTANCE IN NON-DIABETIC PATIENTS WITH RENAL STONE.

Hyperuricemia is an objective risk factor of derangement of fasting serum glucose and type 2 diabetes (T2D), yet whether hyperuricemia has a causative influence on insulin resistance is still debatable. In this study, we tested the hypothesis that lowering uric acid in hyperuricemic nondiabetic subjects might improve insulin resistance. Patients with renal stone and hyperuricemia (n=15) were recruited from the private clinic of Ib-Sina Local Teaching Hospital in Mosul city and prospectively placed on allopurinol (300mg/day) for 6 months. Serum uric acid (SUA), fasting serum glucose (FSG), fasting insulin, and C-peptide were measured using commercial kits. Results confirmed that allopurinol has significantly (P<0.05) reduced c-peptide and insulin together with a non-significant (p>0.05) reduction of serum glucose levels. In conclusion, allopurinol has improved insulin level and glycemic control in a healthy individual, these findings could be used as a template for using allopurinol in diabetic patients to improve glycemic control or future studies could be directed toward structural modification of allopurinol which hopefully might lead to innovation of new antidiabetic drugs.

Association between urate-lowering therapy initiation and all-cause mortality in patients with type 2 diabetes and asymptomatic hyperuricemia.

AIMS: To assess the relationships between urate-lowering therapy (ULT) initiation with all-cause mortality in patients with asymptomatic hyperuricemia and Type 2 Diabetes (T2D). METHODS: This nationwide retrospective cohort study involved patients with T2D and asymptomatic hyperuricemia from 19 academic hospitals across China between 2000 and 2021. The primary exposure was ULT initiation, including allopurinol, febuxostat, or benzbromarone. The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular (CV) and non-CV mortality. Propensity score matching was employed to create a 1:2 matched cohort with balanced likelihood of ULT initiation. Associations between ULT initiation with all-cause and CV mortality were assessed in the matched cohort. RESULTS: Among 42 507 patients, 5028 initiated ULT and 37 479 did not. In the matched cohort, comprising 4871 ULT initiators and 9047 noninitiators, ULT initiation was significantly associated with reduced risk of all-cause mortality (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.71-0.84), CV mortality (HR 0.86; 95% CI, 0.76-0.97), and non-CV mortality (HR 0.72; 95% CI, 0.64-0.80) over an average 3.0 years of follow-up. Among the ULT initiators, post-treatment SUA levels of 360-420 µmol/L was related to a significantly lower risk for all-cause mortality compared to levels >420 µmol/L (HR 0.74; 95% CI, 0.59-0.94) while levels ≤360 µmol/L did not (HR, 0.96; 95% CI, 0.81-1.14), suggesting a U-shaped relationship. CONCLUSIONS: Initiating ULT was associated with a significant reduction in all-cause mortality in patients with T2D and asymptomatic hyperuricemia. Notably, maintaining post-treatment SUA concentrations within 360-420 µmol/L could potentially enhance this reduced mortality.

Comparison of Gout Flares With the Initiation of Treat-to-Target Allopurinol and Febuxostat: A Post-Hoc Analysis of a Randomized Multicenter Trial.

OBJECTIVE: Initiating urate-lowering therapy (ULT) in gout can precipitate arthritis flares. There have been limited comparisons of flare risk during the initiation and escalation of allopurinol and febuxostat, administered as a treat-to-target strategy with optimal anti-inflammatory prophylaxis. METHODS: This was a post-hoc analysis of a 72-week randomized, double-blind, placebo-controlled, noninferiority trial comparing the efficacy of allopurinol and febuxostat. For this analysis, the occurrence of flares was examined during weeks 0 to 24 when ULT was initiated and titrated to a serum urate (sUA) goal of less than 6 mg/dl (<5 mg/dl if tophi). Flares were assessed at regular intervals through structured participant interviews. Predictors of flare, including treatment assignment, were examined using multivariable Cox proportional hazards regression. RESULTS: Study participants (n = 940) were predominantly male (98.4%) and had a mean age of 62.1 years with approximately equal proportions receiving allopurinol or febuxostat. Mean baseline sUA was 8.5 mg/dl and all participants received anti-inflammatory prophylaxis (90% colchicine). In a multivariable model, there were no significant associations of ULT treatment (hazard ratio [HR] 1.17; febuxostat vs allopurinol), ULT-dose escalation (HR 1.18 vs no escalation), prophylaxis type, or individual comorbidity with flare and no evidence of ULT-dose escalation interaction. Factors independently associated with flare risk during ULT initiation/escalation included younger age, higher baseline sUA, and absence of tophi. CONCLUSION: These results demonstrate that gout flare risk during the initiation and titration of allopurinol is similar to febuxostat when these agents are administered according to a treat-to-target strategy using gradual ULT-dose titration and best practice gout flare prophylaxis.

Comparative Cardiovascular Risks of Febuxostat and Allopurinol in Patients with Diabetes Mellitus and Chronic Kidney Disease.

BACKGROUND Hyperuricemia, which is common in chronic kidney disease and diabetes mellitus patients, raises health concerns. Febuxostat, a first-line urate-lowering agent, prompts cardiovascular risk questions, especially in high-risk patients. This study compared the effects of febuxostat and allopurinol on cardiovascular risk in diabetes mellitus and chronic kidney disease patients. MATERIAL AND METHODS This retrospective observational cohort study, conducted using Taiwan's National Health Insurance Research Database, focused on patients diagnosed with chronic kidney disease and diabetes between January 2012 and December 2017. The study population was divided into 2 groups: allopurinol users (n=12 901) and febuxostat users (n=2997). We performed 1: 1 propensity score matching, resulting in subgroups of 2997 patients each. The primary outcomes were assessed using a competing risk model, estimating hazard ratios (HR) for long-term outcomes, including the risks of all-cause hospitalization, hospitalization for heart failure, and hospitalization for cardiovascular interventions. RESULTS Febuxostat users, compared to allopurinol users, had higher all-cause hospitalization (HR: 1.33; 95% confidence interval [CI]: 1.25 to 1.42; P<.001), hospitalization for heart failure (HR: 1.62; 95% CI: 1.43 to 1.83; P<.001), and hospitalization for cardiovascular interventions (HR: 1.51; 95% CI: 1.32 to 1.74; P<.001). Moreover, the adverse effects of febuxostat on cardiac health were consistent across most subgroups. CONCLUSIONS Use of febuxostat in patients with diabetes mellitus and chronic kidney disease is associated with higher cardiovascular risks compared to allopurinol. Prudent evaluation is essential when recommending febuxostat for this at-risk group.

The compelling role of allopurinol in hyperuricemia-induced epilepsy: Unrecognized like tears in rain.

Epilepsy is a common neurological disease characterized by the recurrent, paroxysmal, and unprovoked seizures. It has been shown that hyperuricemia enhances and associated with the development and progression of epilepsy through induction of inflammation and oxidative stress. In addition, uric acid is released within the brain and contributes in the development of neuronal hyperexcitability and epileptic seizure. Brain uric acid acts as damage associated molecular pattern (DAMP) activates the immune response and induce the development of neuroinflammation. Therefore, inhibition of xanthine oxidase by allopurinol may reduce hyperuricemia-induced epileptic seizure and associated oxidative stress and inflammation. However, the underlying mechanism of allopurinol in the epilepsy was not fully elucidated. Therefore, this review aims to revise from published articles the link between hyperuricemia and epilepsy, and how allopurinol inhibits the development of epileptic seizure.

Comparison of the therapeutic effects of febuxostat combined with a low-purine diet and allopurinol combined with a low-purine diet on the improvement of gout patients.

OBJECTIVE: To compare the clinical efficacy of febuxostat combined with a low-purine diet versus allopurinol combined with a low-purine diet in the treatment of gout. METHODS: In this prospective controlled trial, 98 gout patients admitted to our hospital from February 2021 to December 2022 were enrolled as study subjects. Patients were randomly assigned to the study group (febuxostat combined with a low-purine diet) and the control group (allopurinol combined with a low-purine diet), with 49 patients in each group. The therapeutic effect was evaluated based on joint function and serum uric acid levels after treatment, and classified into three levels: markedly effective, effective, and ineffective. The levels of inflammatory factors, including tumor necrosis factor-a (TNF-a), cytokine interleukin-1beta (IL-1ß), and interleukin (IL)-18 (IL-18), were collected. The Numeric Rating Scale (NRS) was used to assess the degree of pain in patients. Clinical indicators before and 6 months after treatment were compared between the two groups. RESULTS: There was no statistically significant difference in age and gender between the two groups. After 6 months of treatment, the effective rate in the study group (48 cases, 97.96%) was higher than that in the control group (42 cases, 85.71%), with a statistically significant difference (p = .027). At the same time, the study group had significantly lower levels of serum uric acid (162.39 µmol/L ± 17.23 µmol/L vs. S198.32 µmol/L ± 18.34 µmol/L, p < .001), creatinine (87.39 mmol/L ± 9.76 mmol/L vs. 92.18 mmol/L ± 9.27 mmol/L, p = .014), total cholesterol (3.65 mmol/L ± 0.65 mmol/L vs. 4.76 mmol/L ± 0.73 mmol/L, p < .001), and triglycerides (1.76 mmol/L ± 0.32 mmol/L vs. 2.28 mmol/L ± 0.41 mmol/L, p < .001) compared to the control group, with statistically significant differences (p < .05). After treatment, the levels of inflammatory factors and degree of pain in the study group were significantly lower than those in the control group (all p < .05). During the treatment process, the incidence of adverse reactions in the study group (2 cases, 4.08%) was lower than that in the control group (9 cases, 18.37%), with a statistically significant difference (p = .025). CONCLUSION: Febuxostat combined with a low-purine diet can reduce inflammatory factors and alleviate the degree of pain in gout patients, significantly improving their clinical symptoms.