Longitudinal analysis of serum urate in prediabetic phase.

OBJECTIVES: Despite the well-established association between prediabetes and hyperuricaemia, knowledge about serum urate (SU) trends during the prediabetic phase is limited. Therefore, we aimed to assess the longitudinal changes of SU in individuals with prediabetes. METHODS: Individuals with prediabetes, defined by initial haemoglobin A1c (HbA1c) levels between 5.7% and 6.4%, were identified using electronic health records from an academic health system (2007-2022). We required at least one SU test before and after the prediabetes diagnosis. The primary outcome was the longitudinal SU trends during the follow-up period, estimated with a multivariable mixed-effects model. Patients were censored at diabetes onset. Marginal effects of covariates on SU changes were estimated. Subsequent analyses examined SU variations in subgroups stratified by age, sex, body mass index (BMI), HbA1c, estimated glomerular filtration rate (eGFR) and metformin use. RESULTS: Out of 25 526 individuals with prediabetes, 1,521 met the SU cohort requirements, contributing to 6,832 SU observations. At baseline, median age was 63 years and 40% were female. Median values were SU 6.3 mg/dl, HbA1c 5.9% and BMI 30 kg/m2. Median follow-up was 7.4 years. Older age, male sex, greater BMI, and higher HbA1c were significant predictors of increased longitudinal SU levels. Individuals with a BMI ≥30 kg/m2 exhibited higher SU levels compared with those with lower BMI values. CONCLUSION: Among individuals with prediabetes, several baseline variables were significant predictors of increased SU levels over time. These longitudinal trends in SU, support the potential for early intervention during the prediabetic phase, possibly reducing the risk of gout.

The impact of altered dietary adenine concentrations on the gut microbiota in Drosophila.

The gut microbiota influences host metabolism and health, impacting diseases. Research into how diet affects gut microbiome dynamics in model organisms is crucial but underexplored. Herein, we examined how dietary adenine affects uric acid levels and the gut microbiota over five generations of Drosophila melanogaster. Wild-type W1118 flies consumed diets with various adenine concentrations (GC: 0%, GL: 0.05%, and GH: 0.10%), and their gut microbiota were assessed via Illumina MiSeq sequencing. Adenine intake significantly increased uric acid levels in the GH group > the GC group. Despite no significant differences in the alpha diversity indices, there were significant disparities in the gut microbiota health index (GMHI) and dysbiosis index (MDI) among the groups. Adenine concentrations significantly altered the diversity and composition of the gut microbiota. High adenine intake correlated with increased uric acid levels and microbial population shifts, notably affecting the abundances of Proteobacteria and Firmicutes. The gut microbiota phenotypes included mobile elements, gram-positive bacteria, biofilm-forming bacteria, and gram-negative bacteria. The significantly enriched KEGG pathways included ageing, carbohydrate metabolism, and the immune system. In conclusion, adenine intake increases uric acid levels, alters gut microbiota, and affects KEGG pathways in Drosophila across generations. This study highlights the impact of dietary adenine on uric acid levels and the gut microbiota, providing insights into intergenerational nutritional effects.

Meta-analysis and systematic review of gout prevalence in the heart/lung transplantation population.

Introduction: Gout may complicate solid organ transplantation with potentially serious consequences. An accurate prevalence of gout in this population is unknown. Objectives: This study aimed to estimate the prevalence of gout in the heart and/or lung transplantation population through a systematic review and meta-analysis. Methods: MEDLINE, Embase, PsycINFO, CENTRAL and Cochrane Library (inception to February 2022) were searched for studies that reported the prevalence and/or incidence of gout in heart and/or lung transplant recipients. Two authors extracted outcomes data. Data were pooled using a random effects model. Overall quality of evidence was assessed using GRADE. Primary outcomes were the prevalence of pre- or post-transplant gout expressed as a prevalence rate (95% CI). Secondary outcomes included risk factors for gout, adverse events, and therapeutic complications of gout treatment. Results: Ten studies were included. Gout prevalence (PR) was 8% pre-transplant (PR = 0.08; 95% CI: 0.05-0.12; 4 studies n = 651) and 6% post-transplant (PR = 0.06; 95% CI: 0.06-0.06; 10 studies n = 45,298). Post-transplant gout prevalence in heart transplant recipients was almost three times higher than lung transplant recipients (PR = 0.16; 95% CI: 0.13-0.20 vs. PR = 0.06; 95% CI: 0.05-0.06 respectively). Patients with a pre-transplant history of gout had a higher risk of developing post-transplant gout than patients without (RR = 3.61; 95% CI: 2.19-5.95). Factors associated with gout and outcomes for heart and/or lung transplant recipients with gout were comprehensively reviewed from the included studies. Conclusion: Gout is highly prevalent in heart and/or lung transplant patients. Pre-transplant gout is predictive of developing symptomatic post-transplant gout. This has significant implications for management of heart/lung transplant patients. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO (CRD42020190632).

The ameliorative and neuroprotective effects of dietary fibre on hyperuricaemia mice: a perspective from microbiome and metabolome.

The effect of single dietary fibre (DF) on lowering uric acid (UA) level has been reported in the literature. However, the potential protective mechanism of DF against potassium oxybate-induced hyperuricaemia (HUA), as modelled by prophylactic administration, remains unclear. The data demonstrate that DF significantly decreased serum and cerebral tissue UA concentrations, inhibited xanthine oxidase expression and activity in the liver and reduced levels of creatinine and urea nitrogen in the serum. Additionally, it mitigated the deposition of amyloid-ß in cerebral tissue. Correlation analysis showed that DF modulated the Toll-like receptor 4/NF-κB signalling pathway, attenuating oxidative stress and inflammatory responses in HUA mice. Additionally, DF helps to maintain the composition of the gut microbiota, reducing harmful Desulfovibrio and enriching beneficial Akkermansia and Ruminococcus populations. The results of the faecal metabolomics analysis indicate that DF facilitates the regulation of metabolic pathways involved in oxidative stress and inflammation. These pathways include pyrimidine metabolism, tryptophan metabolism, nucleotide metabolism and vitamin B6 metabolism. Additionally, the study found that DF has a preventive effect on anxiety-like behaviour induced by HUA. In summary, DF shows promise in mitigating HUA and cognitive deficits, primarily by modulating gut microbiota and metabolites.

Gut microbiota dysbiosis in hyperuricaemia promotes renal injury through the activation of NLRP3 inflammasome.

BACKGROUND: The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal injury. Gut microbiota and gut-derived uremic toxins are critical mediators in the gut-kidney axis that can cause damage to kidney function. Gut dysbiosis has been implicated in various kidney diseases. However, the role and underlying mechanism of the gut microbiota in HUA-induced renal injury remain unknown. RESULTS: A HUA rat model was first established by knocking out the uricase (UOX). HUA rats exhibited apparent renal dysfunction, renal tubular injury, fibrosis, NLRP3 inflammasome activation, and impaired intestinal barrier functions. Analysis of 16S rRNA sequencing and functional prediction data revealed an abnormal gut microbiota profile and activation of pathways associated with uremic toxin production. A metabolomic analysis showed evident accumulation of gut-derived uremic toxins in the kidneys of HUA rats. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the effects of HUA-induced gut dysbiosis on renal injury. Mice recolonized with HUA microbiota exhibited severe renal injury and impaired intestinal barrier functions following renal ischemia/reperfusion (I/R) surgery. Notably, in NLRP3-knockout (NLRP3-/-) I/R mice, the deleterious effects of the HUA microbiota on renal injury and the intestinal barrier were eliminated. CONCLUSION: Our results demonstrate that HUA-induced gut dysbiosis contributes to the development of renal injury, possibly by promoting the production of gut-derived uremic toxins and subsequently activating the NLRP3 inflammasome. Our data suggest a potential therapeutic strategy for the treatment of renal diseases by targeting the gut microbiota and the NLRP3 inflammasome. Video Abstract.

Impact of health literacy, social support, and socioeconomic position on the serum uric acid level in asymptomatic hyperuricaemia patients in China: a structural equation model.

BACKGROUND: Hyperuricaemia (HUA) poses a significant public health challenge on a global scale. It is mostly asymptomatic hyperuricemia (AHU) with unsatisfactory recognition and control rates. The role of health literacy in influencing health outcomes is of utmost importance, and enhancing health literacy is helpful for patients in managing risk factors. Additionally, social support and socioeconomic position (SEP) have been identified as potential factors influencing health. However, the exact relationships between these factors and AHU remain unclear. This study aimed to investigate the status of health literacy among patients with AHU and explore the relationships between health literacy, social support, SEP, and serum uric acid (SUA) levels. METHODS: A cross-sectional study was conducted among 349 participants with AHU in Luzhou, China. The research instruments included a sociodemographic characteristics questionnaire, the Health Literacy Scale for Chronic Patients (HLSCP), and the Social Support Scale (SSRS). The construction of the SEP index was achieved through the application of principal component analysis. Univariate and hierarchical regression analyses were used to evaluate the associations between SEP, social support, health literacy, and SUA levels. Furthermore, structural equation modelling (SEM) was utilized to examine these associations. RESULTS: (1) Most patients exhibited low health literacy (90.18 ± 15.11), and only 44.4% possessed basic health literacy. (2) SEP was positively correlated with SUA levels (ß = 4.086, P < 0.001), and health literacy was negatively related to SUA levels (ß = -0.399, P < 0.001). There was no significant relationship between social support and SUA levels (ß = 0.051, t = 1.085). (3) Health literacy mediated the association between SEP and SUA levels (ß = -0.490, 95% CI: -0.620 to -0.382). SEP had a direct positive effect on SUA levels (ß = 0.723) and health literacy (ß = 0.696), and the total effect of SEP on SUA levels was 0.233. CONCLUSIONS: The findings indicate a low level of health literacy among patients with AHU and suggest that health literacy might play a mediating role in the relationship between SEP and SUA levels. Consequently, future initiatives are recommended to prioritize health literacy and devise appropriate intervention strategies to enhance the self-management capabilities of patients with AHU.

The relationship between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and hyperuricaemia.

PURPOSE: The ratio of non-high-density lipoprotein cholesterol (non-HDL-c) to high-density lipoprotein cholesterol (HDL-c) (NHHR) is a novel comprehensive lipid index. The aim of this study was to investigate the relationship between the NHHR and the prevalence of hyperuricaemia (HUA) in the adult population of the U.S. METHODS: This cross-sectional study collected data from the National Health and Nutrition Examination Survey (NHANES) (2007-2018). HUA was defined as a serum uric acid (SUA) concentration ≥ 7 mg/dL in men and ≥ 6 mg/dL in women. Multivariate logistic regression models and the restricted cubic spline (RCS) method were applied to examine the relationship between the NHHR and the risk of developing HUA. Subgroup analyses and interaction tests were also performed. RESULTS: The prevalence of HUA increased with increasing NHHR values (9.01% vs. 13.38% vs. 17.31% vs. 25.79%, P < 0.001). The NHHR was independently correlated with the risk of developing HUA (OR = 1.10, 95% CI: 1.05-1.16; P < 0.001). Furthermore, the risk of developing HUA was significantly greater among individuals with the highest NHHR quartile than among those with the lowest NHHR quartile (OR = 1.94, 95% CI: 1.62-2.33; P < 0.001). This relationship was consistent across subgroups. According to the RCS analysis, an inverted U-shaped relationship existed between the NHHR and the risk of developing HUA. CONCLUSIONS: The NHHR was closely associated with an increased risk of developing HUA. Further studies on the NHHR could be beneficial for preventing and treating HUA.

Fructose-induced hyperuricaemia - protection factor or oxidative stress promoter?

Accumulating evidence suggests that dietary fructose may play a role in the hyperuricaemia development, but the precise mechanism remains unclear. Hyperuricaemia is characterised by excessive production and deposition of urate crystals, and the metabolism of fructose has been implicated in the elevation of serum urate levels. The association between fructose intake and the risk of hyperuricaemia is explained by the metabolism of fructose in the liver, small intestine, and kidney. Many studies have confirmed the correlation between fructose consumption and an increased risk of developing hyperuricaemia, but more prospective studies to fully elucidate the role of fructose intake in the pathogenesis of hyperuricaemia are needed. It is important to note that maintaining a balanced diet, and lifestyle is crucial when considering fructose intake. Limiting the consumption of products high in added sugars and maintaining a healthy weight can contribute to reducing the risk of hyperuricaemia and associated health complications.

Postbiotic of Pediococcus acidilactici GQ01, a Novel Probiotic Strain Isolated from Natural Fermented Wolfberry, Attenuates Hyperuricaemia in Mice through Modulating Uric Acid Metabolism and Gut Microbiota.

Hyperuricaemia (HUA) is a disorder of purine metabolism, which manifests itself as an increase in uric acid production and a decrease in uric acid excretion, as well as a change in the structure of the intestinal microbiota. Most of the drugs currently used to treat HUA have significant side effects, and it is essential to find a treatment for HUA that is free of side effects. In this study, a novel strain, Pediococcus acidilactici GQ01, was screened from natural fermented wolfberry. The effects of both live bacteria GQ01 and its heat-killed G1PB postbiotic on HUA were investigated. The results showed that both probiotic GQ01 and G1PB postbiotics could effectively decrease blood uric acid, creatinine, and urea nitrogen levels in the HUA mice model. P. acidilactici GQ01 was more effective in inhibiting ADA activity, while G1PB postbiotics was more effective in inhibiting XOD activity. Meanwhile, GQ01 and G1PB were able to ameliorate liver and kidney tissue injury, upregulate the expression of ABCG2 in kidney and XOD gene in liver, downregulate the protein expression of URAT1 and GLUT9 in kidney, and therefore reduce the value of blood uric acid by decreasing the uric acid reabsorption and increasing the excretion of uric acid. Additionally, both probiotics and postbiotics could regulate the intestinal microbiota structure of HUA mice, so as to bring the dysfunctional intestinal composition back to normal. Furthermore, P. acidilactici GQ01 and G1PB postbiotics can increase the levels of acetic acid, propionic acid, and butyric acid in the intestinal tract, improve the intestinal function, and maintain the healthy homeostatic state of the intestinal tract. In summary, P. acidilactici GQ01 and its G1PB postbiotics may be developed as functional food or drug materials capable of treating HUA.

Treatment with Rasburicase in Hospitalized Patients with Cardiorenal Syndrome: Old Treatment, New Scenario.

Cardiorenal syndrome (CRS) involves joint dysfunction of the heart and kidney. Acute forms share biochemical alterations like hyperuricaemia (HU) with tumour lysis syndrome (TLS). The mainstay treatment of acute CRS with systemic overload is diuretics, but rasburicase is used in TLS to prevent and treat hyperuricaemia. An observational, retrospective study was performed to assess the effectiveness and safety of a single dose of rasburicase in hospitalized patients with cardiorenal syndrome, worsening renal function and uric acid levels above 9 mg/dL. Rasburicase improved diuresis and systemic congestion in the 35 patients included. A total of 86% of patients did not need to undergo RRT, and early withdrawal was possible in the remaining five. Creatinine (Cr) decreased after treatment with rasburicase from a peak of 3.6 ± 1.27 to 1.79 ± 0.83 mg/dL, and the estimated glomerular filtration rate (eGFR) improved from 17 ± 8 to 41 ± 20 mL/min/1.73 m2 (p = 0.0001). The levels of N-terminal type B Brain Natriuretic Peptide (Nt-ProBNP) and C-reactive protein (CRP) were also significantly reduced. No relevant adverse events were detected. Our results show that early treatment with a dose of rasburicase in patients with CRS and severe HU is effective to improve renal function and systemic congestion, avoiding the need for sustained extrarenal clearance, regardless of comorbidities and ventricular function.

Correlation Between Impaired Sensitivity to Thyroid Hormones and Serum Uric Acid in Female Patients With Obesity and After Laparoscopic Sleeve Gastrectomy.

OBJECTIVE: An alterable risk factor for hyperuricemia is obesity. Additionally, obese people may have a moderate form of acquired resistance to thyroid hormones. Thyrotropin, thyroid hormones, and obesity all interact subtly. However, the connection between thyroid hormone sensitivity and hyperuricemia in obese patients both before and after laparoscopic sleeve gastrectomy (LSG) has not yet been clarified. The objective of our study was to investigate the connection between impaired thyroid hormone sensitivity and elevated uric acid (UA) levels before and after LSG. METHODS: In total, 1054 euthyroid patients with obesity (481 males, 573 females), 248 (143 female patients) of whom underwent subsequent LSG, were enrolled in this retrospective study. Anthropometric measurements and thyroid hormone and UA levels were taken before and 3 months after LSG. RESULTS: Female patients with obesity with impaired sensitivity to thyroid hormones had higher UA levels (P for trend <.01). The odds ratio of the fourth vs first quartile of thyroid feedback quantile index, thyrotropin index, and thyrotropin-thyroxine resistance index were 4.285 (confidence interval: 1.360-13.507), 3.700 (confidence interval: 1.276-10.729), and 2.839 (confidence interval: 1.014-7.948), respectively, with robust relationships with female hyperuricemia (all P < .05). However, there was only a positive correlation between the decline in UA levels and thyroid feedback quantile index, thyrotropin, and thyrotropin-thyroxine resistance index in female patients following LSG. CONCLUSION: Female hyperuricemia is correlated with higher thyroid hormone resistance index scores. Resistance to thyroid hormones was greatly improved by LSG. The decrease in UA levels after surgery is correlated with the improvement of thyroid hormone resistance after LSG.

Changes in Serum Urate Levels after Bariatric Surgery in Patients with Obesity: An Observational Study.

BACKGROUND: Obesity is a risk factor for hyperuricemia and gout, while weight reduction can reduce urate levels. The aim of this study was to examine the effect of bariatric surgery on longitudinal serum urate levels. METHODS: We performed a retrospective observational study of 283 patients who had undergone bariatric surgery [237 (83.7%) gastric bypass, 34 (12.0%) sleeve gastrectomy and 12 (4.2%) gastric banding] and were followed up for 2 years. The results shown represent mean (standard deviation). RESULTS: Bariatric surgery was associated with significant reduction in serum urate from baseline level of 0.343 (0.086) mmol/L to 0.296 (0.076) mmol/L (p < 0.001) at 12 months and 0.286 (0.073) mmol/L (p < 0.001) at 24 months, including in men and women, and in patients with or without diabetes. Patients with elevated urate levels at baseline, who comprised 27.2% of the total cohort, achieved reduction in levels by 4 months. CONCLUSION: Bariatric surgery leads to significant reduction in serum urate levels at 12 and 24 months. This could reduce incidence of gout and need for prophylactic medication(s).

Life's Essential 8, Life's Simple 7 and the odds of hyperuricaemia: results from the China Multi-Ethnic Cohort Study.

Objective: Life's Essential 8 (LE8) is a new comprehensive metric based on Life's Simple 7 (LS7). Few studies have investigated the association between LE8 and the odds of hyperuricaemia (HUA). This study examined the association between LE8, LS7 with odds of HUA. Methods: We cross-sectionally analysed data from the China Multi-Ethnic Cohort (CMEC) study. LE8 and LS7 were categorized as low, moderate and high. The CMEC provided an ideal and unique opportunity to characterize the association between LE8, LS7 and the odds of HUA. Results: Of the 89 823 participants, 14 562 (16.2%) had HUA. A high level of LE8 was associated with lower odds of HUA after full adjustment. The adjusted odds ratios (ORs) were 1 (reference), 0.70 (95% CI 0.67, 0.73) and 0.45 (0.42, 0.48) across low, moderate and high LE8 groups, respectively (Ptrend < 0.001). Similar results were observed in LS7 and HUA. The adjusted ORs were 1 (reference), 0.68 (95% CI 0.65, 0.71) and 0.46 (95% CI 0.43, 0.49) across low, moderate and high LS7 groups, respectively (Ptrend < 0.001). There were significant interactions between LE8 and age, gender, ethnicity and drinking habits on HUA. Receiver operating characteristics analysis showed that the area under the curve for LE8 and LS7 were similar (0.638 and 0.635, respectively). Conclusion: This study indicated a clearly inverse gradient association between the cardiovascular health metrics LE8 and LS7 and the odds of HUA.

Interaction of genetic variation at ADH1B and MLXIPL with alcohol consumption for elevated serum urate level and gout among people of European ethnicity.

BACKGROUND: Alcohol consumption is a risk factor for hyperuricaemia and gout. Multiple single-nucleotide polymorphisms (SNPs) have been identified as associated with both alcohol consumption and serum urate or gout in separate genome-wide association studies (GWAS). This study aimed to identify and characterise interactions between these shared signals of genetic association and alcohol consumption for serum urate level, hyperuricaemia, and gout. METHODS: This research was conducted using the UK Biobank resource. The association of alcohol consumption with serum urate and gout was tested among 458,405 European participants. Candidate SNPs were identified by comparing serum urate, gout, and alcohol consumption GWAS for shared signals of association. Multivariable-adjusted linear and logistic regression analyses were conducted with the inclusion of interaction terms to identify SNP-alcohol consumption interactions for association with serum urate level, hyperuricaemia, and gout. The nature of these interactions was characterised using genotype-stratified association analyses. RESULTS: Alcohol consumption was associated with elevated serum urate and gout. For serum urate level, non-additive interactions were identified between alcohol consumption and rs1229984 at the ADH1B locus (P = 3.0 × 10-44) and rs6460047 at the MLXIPL locus (P = 1.4 × 10-4). ADH1B also demonstrated interaction with alcohol consumption for hyperuricaemia (P = 7.9 × 10-13) and gout (P = 8.2 × 10-9). Beer intake had the most significant interaction with ADH1B for association with serum urate and gout among men, while wine intake had the most significant interaction among women. In the genotype-stratified association analyses, ADH1B and MLXIPL were associated with serum urate level and ADH1B was associated with hyperuricaemia and gout among consumers of alcohol but not non-consumers. CONCLUSIONS: In this large study of European participants, novel interactions with alcohol consumption were identified at ADH1B and MLXIPL for association with serum urate level and at ADH1B for association with hyperuricaemia and gout. The association of ADH1B with serum urate and gout may occur through the modulation of alcohol metabolism rate among consumers of alcohol.

Using intravoxel incoherent motion imaging to evaluate uric acid-induced renal injury and efficacy after treatment.

OBJECTIVES: To validate the feasibility of intravoxel incoherent motion imaging (IVIM) for monitoring renal injury and uric acid-lowering efficacy in a rat model of hyperuricaemia. METHODS: A total of 92 rats were analysed and categorized into 4 groups: control (CON), hyperuricaemia (HUA), allopurinol intervention (ALL), and combined intervention (COM). Eight rats were randomly selected from each group and underwent IVIM scanning on days 0, 1, 3, 5, 7, and 9. Quantitative magnetic resonance values (D, D*, and f values) measured from the different renal anatomical regions. Quantitative histopathological analysis was performed to assess renal tubular injury using neutrophil gelatinase-associated lipocalin (NGAL), and renal fibrosis using alpha-smooth-muscle-actin (α-SMA). Pearson's correlation analysis was used to determine the correlation between IVIM-derived parameters and the expression of NGAL and α-SMA. RESULTS: The D values of the HUA, ALL, and COM groups generally showed a downward trend over time, and this fluctuation was most significant in the HUA group. The D values showed significant intergroup differences at each point, whereas only a few discrepancies were found in the D* and f values. In addition, the renal D value was negatively correlated with the positive staining rates for NGAL and α-SMA (P < .05), except for the lack of correlation between Dos and α-SMA (P > .05). CONCLUSION: IVIM could be a noninvasive and potential assessment modality for the evaluation of renal injury induced by hyperuricaemia and its prognostic efficacy. ADVANCES IN KNOWLEDGE: IVIM could be a surrogate manner in monitoring renal damage induced by hyperuricaemia and its treatment evaluation.

Hyperuricaemia-associated all-cause mortality risk effect is increased by non-impaired kidney function - Is renal hyperuricaemia less dangerous?

BACKGROUND: Both hyperuricaemia and chronic kidney disease are known mortality risk factors. This study examined the modifying effect of renal function on hyperuricaemia-associated mortality risk, which is an issue that has not been studied before. METHODS: Data on levels of serum uric acid (SUA), creatinine, cystatin C and other variables of persons aged 52-76 years were collected. Persons with SUA >410 µmol/L (75th percentile) were classified as clearly hyperuricaemic and persons with eGFR of ≤67 ml/min (25th percentile) as having reduced kidney function. RESULTS: Reduced kidney function was associated with higher mortality in both SUA groups. When compared to individuals with SUA ≤410 µmol/L and eGFR >67 ml/min the hazard ratio (HR) for all-cause mortality was 1.53 (95 % CI: 1.26-1.84) in clearly hyperuricaemic persons with reduced kidney function, 1.26 (95 % CI: 1.02-1.55) in clearly hyperuricaemic persons with eGFR of >67 ml/min and 1.15 (95 % CI: 0.96-1.39) in persons with SUA ≤410 µmol/L and reduced kidney function. The HR for hyperuricaemia-related premature death was lowest in individuals with reduced eGFR, and it rose strikingly as the eGFR increased above 90 ml/min. CONCLUSIONS: Reduced kidney function is a risk factor for mortality both in individuals with normal and elevated SUA. The hyperuricaemia-associated mortality risk is remarkably higher in individuals with normal kidney function than in individuals with reduced kidney function. Presumably overproduction of uric acid (metabolic hyperuricaemia) is a separate and more deleterious entity than hyperuricaemia resulting from reduced renal excretion of uric acid (renal hyperuricaemia).

Comparative studies of xanthine oxidase inhibitors viz. allopurinol and febuxostat against induced hyperuricaemia in a poultry model.

In this study, an attempt was made to evaluate the relative efficacy of two important anti-gout agents, viz. allopurinol and febuxostat, in the control of hyperuricaemia/gout using a poultry model. A 21-day study was conducted on 48 Vencobb-400 broiler chicks randomly divided into four groups. In one group hyperuricaemia/gout was induced by the oral administration of diclofenac (group D); in two other groups the ameliorative effect of the two drugs under study was investigated by providing both simultaneously, i.e. diclofenac and allopurinol (group DA), diclofenac and febuxostat (group DF); and the fourth group was kept un-induced and untreated as a control (group C). Both allopurinol and febuxostat inhibit xanthine oxidase enzymes, thereby reducing the production of uric acid. The birds kept on diclofenac alone exhibited the highest level of hyperuricaemia, clinical signs of gout, and overt adverse changes in the visceral organs, whereas these changes were lesser in allopurinol- and febuxostat-treated groups. Furthermore, haematological, biochemical, patho-morphological, and ultra-structural studies using transmission electron microscopy were carried out to evaluate the pathology and, thus, the ameliorative effect of allopurinol and febuxostat. The findings proved that allopurinol and febuxostat carry definite ameliorative potential as anti-hyperuricemic and anti-gout agents in poultry, which was better expressed by febuxostat compared to allopurinol.

In vivo comprehensive metabolite profiling of esculetin and esculin derived from chicory in hyperuricemia rats using ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap high-resolution mass spectrometry.

Chicory, renowned for its multifaceted benefits, houses two vital coumarins, esculetin and esculin, both instrumental in reducing uric acid. This study emphasizes the metabolic pathways of esculetin and esculin under both standard and hyperuricemia conditions. Hyperuricemia was induced in Sprague-Dawley rats using oxonic acid potassium salt (300 mg·kg-1 ) and a 10% fructose water regimen over 21 days. Leveraging the ultra-high-performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high resolution mass spectrometry, we analyzed the fragmentation behaviors of esculetin and esculin in rat bio-samples. Post oral-intake of esculetin or esculin, a notable dip in serum uric acid levels was observed in hyperuricemia rats. The investigation unveiled 24 esculetin metabolites and 14 for esculin. The metabolic pathways of both compounds were hydrolysis, hydroxylation, hydrogenation, dehydroxylation, glucuronidation, sulfation, and methylation. Interestingly, certain metabolites presented variations between standard and hyperuricemia rats, indicating that elevated levels of uric acid may affect enzyme activity linked to these metabolic reactions. This is the first systematic study on comparison of metabolic profiles of esculetin and esculin in both normal and hyperuricemia states, which was helpful to enrich our understanding of the complicated structure-activity relationships between esculin and esculetin and shed light to their action mechanism.

Eupatilin inhibits xanthine oxidase in vitro and attenuates hyperuricemia and renal injury in vivo.

Uric acid (UA) is the final metabolite of purines in the liver that can cause hyperuricemia at high levels. The kidneys are the main excretory organs for UA. The excessive accumulation of UA in the kidneys causes the development of hyperuricemia that often leads to renal injury. Eupatilin (Eup) is a flavonoid natural product that possesses various pharmacological properties such as antioxidant, anti-cancer, and anti-inflammatory. We were interested in exploring the potential role of Eup in lowering UA and nephroprotective. We initially investigated the effects of Eup on xanthin oxidase (XOD) activity in vitro, followed by investigating its ability to lower UA levels, anti-inflammatory effects, nephroprotective effects, and the underlying mechanisms using hyperuricemia rats sustained at high UA level. The results showed that Eup had an inhibitory effect on XOD activity in vitro and significantly reduced serum UA, creatinine, BUN, IL-1ß and IL-6 levels in hyperuricemic rats, ameliorating inflammation, renal oxidative stress and pathological injury. Furthermore, Eup inhibited ADA and XOD enzyme activities in the liver and serum and modulated GLUT9, URAT1 and ABCG2 protein expression in the kidneys and ileum. Our findings provide a scientific basis for suggesting Eup as an option for a potential treatment for hyperuricemia.