Hyperuricemia as an independent risk factor for achilles tendon rupture in male: a case-control study.

OBJECTIVE: To study the correlation between achilles tendon rupture (ATR) and hyperuricemia, also verify the known risk factors for ATR. METHODS: A retrospective review of 488 subjects was performed (182 with Achilles tendon rupture, 306 controls with ankle sprains). Demographic variables and risk factors for rupture were tabulated and compared. The baseline data and related indicators were compared, and the risk factors of ATR were analyzed by constructing a binary logistic regression model. RESULTS: Univariate logistic analysis showed that BMI, smoking, and hyperuricemia were risk factors for the development of ATR (OR = 1.65, 95%CI 1.13-2.42, P = 0.01; OR = 1.47, 95%CI 1.00-2.24, P < 0.05; OR = 2.85, 95%CI 1.84-4.42, P < 0.01). Multifactorial analysis showed that BMI ≥ 25 kg/m2, smoking, and hyperuricemia were independent risk factors for the development of ATR (OR = 1.66, 95%CI 1.11-2.49, P = 0.01; OR = 2.15, 95%CI 1.28-3.60, P < 0.01; OR = 3.06, 95%CI 1.92-4.89, P < 0.01). Among the blood biochemical indicators, total cholesterol (TC) and uric acid (UA) were independent risk factors for the occurrence of ATR (OR = 1.54, 95% CI 1.12-2.12, P = 0.01; OR = 1.01, 95% CI 1.01-1.01, P < 0.01). CONCLUSION: Our study confirmed that, as in previous results, higher BMI, smoking, and total cholesterol are risk factors for ATR, Hyperuricemia may contribute to the development of ATR, and adjunctive tests for TC and UA in the blood biochemistry may be helpful in predicting the risk of ATR.

Renal interstitial fibrotic assessment using non-Gaussian diffusion kurtosis imaging in a rat model of hyperuricemia.

BACKGROUND: To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia. METHODS: A hyperuricemia rat model was established, and the rats were randomly split into the hyperuricemia (HUA), allopurinol (AP), and AP + empagliflozin (AP + EM) groups (n = 19 per group). Also, the normal rats were selected as controls (CON, n = 19). DKI was performed before treatment (baseline) and on days 1, 3, 5, 7, and 9 days after treatment. The DKI indicators, including mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) of the cortex (CO), outer stripe of the outer medulla (OS), and inner stripe of the outer medulla (IS) were acquired. Additionally, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and nuclear factor kappa B (NF-κB) immunostaining were used to reveal renal histopathological changes at baseline, 1, 5, and 9 days after treatment. RESULTS: The HUA, AP, and AP + EM group MKOS and MKIS values gradually increased during this study. The HUA group exhibited the highest MK value in outer medulla. Except for the CON group, all the groups showed a decreasing trend in the FA and MD values of outer medulla. The HUA group exhibited the lowest FA and MD values. The MKOS and MKIS values were positively correlated with Masson's trichrome staining results (r = 0.687, P < 0.001 and r = 0.604, P = 0.001, respectively). The MDOS and FAIS were negatively correlated with Masson's trichrome staining (r = -626, P < 0.0014 and r = -0.468, P = 0.01, respectively). CONCLUSION: DKI may be a non-invasive method for monitoring renal interstitial fibrosis induced by hyperuricemia.

Associations between hyperuricemia and ultrasound-detected knee synovial abnormalities in middle-aged and older population: a cross-sectional study.

OBJECTIVES: Knee synovial abnormalities, potentially treatment targets for knee pain and osteoarthritis, are common in middle-aged and older population, but its etiology remains unclear. We examined the associations between hyperuricemia and knee synovial abnormalities detected by ultrasound in a general population sample. METHODS: Participants aged ≥ 50 years were from a community-based observational study. Hyperuricemia was defined as serum urate (SU) level > 416 µmol/L in men and > 357 µmol/L in women. Ultrasound of both knees was performed to determine the presence of synovial abnormalities, i.e., synovial hypertrophy, effusion, or Power Doppler signal (PDS). We examined the relation of hyperuricemia to prevalence of knee synovial abnormalities and its laterality, and the dose-response relationships between SU levels and the prevalence of knee synovial abnormalities. RESULTS: In total, 3,405 participants were included in the analysis. Hyperuricemia was associated with higher prevalence of knee synovial abnormality (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI]: 1.02 to 1.43), synovial hypertrophy (aOR = 1.33, 95% CI: 1.05 to 1.68), and effusion (aOR = 1.21, 95% CI: 1.02 to 1.44), respectively. There were dose-response relationships between SU levels and synovial abnormalities. Additionally, the hyperuricemia was more associated with prevalence of bilateral than with that of unilateral knee synovial abnormality, synovial hypertrophy, or effusion; however, no significant association was observed between hyperuricemia and PDS. CONCLUSION: In this population-based study we found that hyperuricemia was associated with higher prevalence of knee synovial abnormality, synovial hypertrophy and effusion, suggesting that hyperuricemia may play a role in pathogenesis of knee synovial abnormalities.

Resveratrol Improves Hyperuricemia and Ameliorates Renal Injury by Modulating the Gut Microbiota.

Resveratrol (RES) has been reported to prevent hyperuricemia (HUA); however, its effect on intestinal uric acid metabolism remains unclear. This study evaluated the impact of RES on intestinal uric acid metabolism in mice with HUA induced by a high-fat diet (HFD). Moreover, we revealed the underlying mechanism through metagenomics, fecal microbiota transplantation (FMT), and 16S ribosomal RNA analysis. We demonstrated that RES reduced the serum uric acid, creatinine, urea nitrogen, and urinary protein levels, and improved the glomerular atrophy, unclear renal tubule structure, fibrosis, and renal inflammation. The results also showed that RES increased intestinal uric acid degradation. RES significantly changed the intestinal flora composition of HFD-fed mice by enriching the beneficial bacteria that degrade uric acid, reducing harmful bacteria that promote inflammation, and improving microbial function via the upregulation of purine metabolism. The FMT results further showed that the intestinal microbiota is essential for the effect of RES on HUA, and that Lactobacillus may play a key role in this process. The present study demonstrated that RES alleviates HFD-induced HUA and renal injury by regulating the gut microbiota composition and the metabolism of uric acid.

L-shaped association between lean body mass to visceral fat mass ratio with hyperuricemia: a cross-sectional study.

BACKGROUND: Insufficient attention has been given to examining the correlation between body composition and hyperuricemia, leading to inconsistent findings. The primary objective of this research is to explore the association between lean body mass index (LMI), visceral fat mass index (VFMI), and hyperuricemia. A specific emphasis will be placed on assessing the link between the ratio of lean body mass to visceral fat mass (LMI/VFMI) and hyperuricemia. METHODS: The present study employed a cross-sectional design and involved a total of 9,646 individuals who participated in the National Health and Nutrition Examination Survey (NHANES). To explore the associations among the variables, logistic and linear regressions were employed. Additionally, subgroup analyses and sensitivity analyses were conducted based on various characteristics. RESULTS: The results showed that LMI was positively associated with hyperuricemia (for Per-SD: OR = 1.88, 95%CI: 1.75, 2.01; for quartiles [Q4:Q1]: OR = 5.37, 95%CI: 4.31, 6.69). Meanwhile, VFMI showed a positive association with hyperuricemia (for Per-SD: OR = 2.02, 95%CI: 1.88, 2.16; for quartiles [Q4:Q1]: OR =8.37, 95%CI: 6.70, 10.47). When considering the effects of In LMI/VFMI, an L-shaped negative association with hyperuricemia was observed (for Per-SD: OR = 0.45, 95%CI: 0.42, 0.49; for quartiles [Q4:Q1]: OR = 0.16, 95%CI: 0.13, 0.20). Subgroup and sensitivity analyses demonstrated the robustness of this association across different subgroups. Additionally, the segmented regression analysis indicated a saturation effect of 5.64 for the In LMI/VFMI with hyperuricemia (OR = 0.20, 95%CI: 0.17, 0.24). For every 2.72-fold increase of In LMI/VFMI, the risk of hyperuricemia was reduced by 80%. CONCLUSION: The LMI/VFMI ratio is non-linearly associated with serum uric acid. Whether this association is causal needs to be confirmed in further longitudinal studies or Mendelian randomization.

Serum Uric Acid and Serum Lipid Levels in Patients with Acute Ischemic Stroke Admitted in Mymensingh Medical College Hospital.

Stroke is the second-leading cause of death and also a leading cause of combined death and disability. In Bangladesh, stroke prevalence is 11.39 per 1000 population, but highest prevalence of stroke is 14.71 per 1000 population in the Mymensingh division. Hyperuricemia has been reported as an independent risk factor for stroke in different studies and a significant association between serum uric acid and dyslipidemia has also been stated. On the contrary, some studies suggest that uric acid has a neuroprotective role. This cross-sectional study was completed in the Medicine Department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh from March 2021 to January 2023. In this cross-sectional study, 352 adult acute ischemic stroke patients were included from the Medicine Department of Mymensingh Medical College Hospital. Serum uric acid and fasting serum lipid levels were measured within 48 hours of admission. The mean age ±SD of the respondents was 61.9±12.8 years. Hyperuricemia was found among 18.2% of respondents, whose mean ±SD serum uric acid was 5.7±1.9 mg/dl. Dyslipidemia was present in 88.4% of patients. The mean ±SD of the National Institutes of Health Stroke Scale (NIHSS) score was 12.0±5.9. Most of the patients (65.6%) were suffering from moderate stroke, followed by moderate to severe stroke (15.1%), severe stroke (10.8%) and minor stroke (8.5%). After multiple linear regressions, the independent variables age, gender, serum uric acid and total cholesterol were found to be significant predictors of the NIHSS score of the respondents. In conclusion, the majority of acute ischemic stroke patients have an association with dyslipidemia, but only around one-fifth of patients have hyperuricemia. There is a significant association of high serum uric acid and high serum total cholesterol with stroke severity (NIHSS score). But low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and, triglycerides have no association with stroke severity.

Assessment of the correlation between KAP scores regarding sugar-sweetened beverage consumption and hyperuricemia amongst Chinese young adults.

BACKGROUND: The prevalence of hyperuricemia in China has been consistently increasing, particularly among the younger generation. The excessive consumption of sugar-sweetened beverages is associated with hyperuricemia. This study examined the knowledge, attitudes, and practices (KAP) of Chinese young adults regarding sugar-sweetened beverage consumption and the correlation with hyperuricemia. METHODS: This cross-sectional investigation was conducted from June 28th, 2023, to July 21st, 2023, and enrolled Chinese young adults. Demographics and KAP were evaluated using a questionnaire (Cronbach's α = 0.787). Factors influencing KAP scores were analyzed using multivariable analyses. RESULTS: A total of 1288 valid questionnaires were analyzed. The median knowledge, attitude, and practice scores were 16 (12,19)/22, 22 (20,24)/30, and 27.5 (23,31.75)/40. The multivariable analysis showed that bachelor's/associate education (OR = 1.912, 95%CI: 1.128-3.239), white collar/employee (OR = 0.147, 95%CI: 0.105-0.206), educator (OR = 0.300, 95%CI: 0.174-0.518), healthcare worker (OR = 0.277, 95%CI: 0.188-0.407), not suffering from hyperuricemia (OR = 0.386, 95%CI: 0.253-0.590), and not having gout (OR = 0.456, 95%CI: 0.282-0.736) were independently associated with knowledge. Age 26-30 (OR = 1.470, 95%CI: 1.052-2.052), age 31-35 (OR = 1.489, 95%CI: 1.097-2.022), age 36-40 (OR = 0.328, 95%CI: 1.010-1.746), age 41-44 (OR = 1.548, 95%CI: 1.091-2.198), and not having hyperuricemia (OR = 0.512, 95%CI: 0.345-0.760) were independently associated with attitude. White collar/employee (OR = 0.386, 95%CI: 0.285-0.521), educator (OR = 0.534, 95%CI: 0.317-0.899), healthcare worker (OR = 0.341, 95%CI: 0.236-0.493), having siblings (OR = 0.725, 95%CI: 0.573-0.917), and not suffering from hyperuricemia (OR = 0.442, 95%CI: 0.296-0.659), were independently associated with practice. CONCLUSION: Chinese young adults display moderate KAP toward sugar-sweetened beverages. Notably, an association was observed between hyperuricemia and each KAP dimension.

Development and Internal Validation of a Risk Prediction Model for Carotid Atherosclerosis in the Hyperuricemia Population.

Purpose: The aim of this study was to identify independent risk factors for carotid atherosclerosis (CAS) in a population with hyperuricemia (HUA) and develop a CAS risk prediction model. Patients and Methods: This retrospective study included 3579 HUA individuals who underwent health examinations, including carotid ultrasonography, at the Zhenhai Lianhua Hospital in Ningbo, China, in 2020. All participants were randomly assigned to the training and internal validation sets in a 7:3 ratio. Multivariable logistic regression analysis was used to identify independent risk factors associated with CAS. The characteristic variables were screened using the least absolute shrinkage and selection operator combined with 10-fold cross-validation, and the resulting model was visualized by a nomogram. The discriminative ability, calibration, and clinical utility of the risk model were validated using the receiver operating characteristic curve, calibration curve, and decision curve analysis. Results: Sex, age, mean red blood cell volume, and fasting blood glucose were identified as independent risk factors for CAS in the HUA population. Age, gamma-glutamyl transpeptidase, serum creatinine, fasting blood glucose, total triiodothyronine, and direct bilirubin, were screened to construct a CAS risk prediction model. In the training and internal validation sets, the risk prediction model showed an excellent discriminative ability with the area under the curve of 0.891 and 0.901, respectively, and a high level of fit. Decision curve analysis results demonstrated that the risk prediction model could be beneficial when the threshold probabilities were 1-87% and 1-100% in the training and internal validation sets, respectively. Conclusion: We developed and internally validated a risk prediction model for CAS in a population with HUA, thereby contributing to the CAS early identification.

Large-scale cross-ancestry genome-wide meta-analysis of serum urate.

Hyperuricemia is an essential causal risk factor for gout and is associated with cardiometabolic diseases. Given the limited contribution of East Asian ancestry to genome-wide association studies of serum urate, the genetic architecture of serum urate requires exploration. A large-scale cross-ancestry genome-wide association meta-analysis of 1,029,323 individuals and ancestry-specific meta-analysis identifies a total of 351 loci, including 17 previously unreported loci. The genetic architecture of serum urate control is similar between European and East Asian populations. A transcriptome-wide association study, enrichment analysis, and colocalization analysis in relevant tissues identify candidate serum urate-associated genes, including CTBP1, SKIV2L, and WWP2. A phenome-wide association study using polygenic risk scores identifies serum urate-correlated diseases including heart failure and hypertension. Mendelian randomization and mediation analyses show that serum urate-associated genes might have a causal relationship with serum urate-correlated diseases via mediation effects. This study elucidates our understanding of the genetic architecture of serum urate control.

Gender-specific association between blood cell parameters and hyperuricemia in high-altitude areas.

Background: Hyperuricemia is a common metabolic disorder linked to various health conditions. Its prevalence varies among populations and genders, and high-altitude environments may contribute to its development. Understanding the connection between blood cell parameters and hyperuricemia in high-altitude areas can shed light on the underlying mechanisms. This study aimed to investigate the relationship between blood cell parameters and hyperuricemia in high-altitude areas, with a particular focus on gender differences. Methods: We consecutively enrolled all eligible Tibetan participants aged 18-60 who were undergoing routine medical examinations at the People's Hospital of Chaya County between January and December 2022. During this period, demographic and laboratory data were collected to investigate the risk factors associated with hyperuricemia. Results: Among the participants, 46.09% were diagnosed with hyperuricemia. In the male cohort, significant correlations were found between serum uric acid (SUA) levels and red blood cell (RBC) count, creatinine (Cr). Urea, alanine transaminase (ALT), and albumin (ALB). Notably, RBC exhibited the strongest association. Conversely, in the female cohort, elevated SUA levels were associated with factors such as white blood cell (WBC) count. Urea, ALT, and ALB, with WBC demonstrating the most significant association. Further analysis within the female group revealed a compelling relationship between SUA levels and specific white blood cell subtypes, particularly neutrophils (Neu). Conclusion: This study revealed gender-specific associations between SUA levels and blood cell parameters in high-altitude areas. In males, RBC count may play a role in hyperuricemia, while in females, WBC count appears to be a significant factor. These findings contribute to our understanding of metabolic dynamics in high-altitude regions but require further research for comprehensive mechanistic insights.

Interaction between anemia and hyperuricemia in the risk of all-cause mortality in patients with chronic kidney disease.

Aim: Both hyperuricemia and anemia are not only the manifestation of chronic kidney disease (CKD) but also related to its occurrence and development. A recent study has found that there was a synergetic effect between hyperuricemia and anemia on new-onset CKD. Herein we aimed to explore the roles of hyperuricemia and anemia in the all-cause mortality in patients with CKD. Methods: Data of adult patients with CKD were extracted from the National Health and Nutrition Examination Surveys (NHANES) database in 2009-2018 in this retrospective cohort study. Weighted univariate and multivariate COX regression analyses were used to investigate the associations of hyperuricemia and anemia with all-cause mortality, and the evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). The interaction effect between hyperuricemia and anemia on the risk of all-cause mortality was assessed via relative excess risk due to interaction (RERI) and attributable proportion of interaction (AP). Subgroup analyses of age, gender, CVD, hypertension, DM, and cancer were also performed to assess this interaction effect. Results: Among 3,678 eligible patients, 819 died from all causes. After adjusting for covariables, we found that CKD patients with anemia (HR = 1.72, 95%CI: 1.42-2.09) or hyperuricemia (HR = 1.21, 95%CI: 1.01-11.45) had a higher risk of all-cause mortality. There was a potential synergetic effect between anemia and hyperuricemia on all-cause mortality, with RERI of 0.630 and AP of 0.291. Moreover, this synergetic effect was also observed in ≥65 years old (AP = 0.330), male (AP = 0.355), hypertension (AP = 0.736), non-hypertension (AP = 0.281), DM (AP = 0.371), and cancer (AP = 0.391) subgroups. Conclusion: A potential synergetic effect between anemia and hyperuricemia on all-cause mortality was found in patients with CKD. However, further studies are needed to clarify the causal relationship between them.

Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model.

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

Comparison of seven anthropometric indexes to predict hypertension plus hyperuricemia among U.S. adults.

Purpose: This study aims to compare the association of hypertension plus hyperuricemia (HTN-HUA) with seven anthropometric indexes. These include the atherogenic index of plasma (AIP), lipid accumulation product (LAP), visceral adiposity index (VAI), triglyceride-glucose index (TyG), body roundness index (BRI), a body shape index (ABSI), and the cardiometabolic index (CMI). Methods: Data was procured from the National Health and Nutrition Examination Survey (NHANES), which recruited a representative population aged 18 years and above to calculate these seven indexes. Logistic regression analysis was employed to delineate their correlation and to compute the odds ratios (OR). Concurrently, receiver operating characteristic (ROC) curves were utilized to evaluate the predictive power of the seven indexes. Results: A total of 23,478 subjects were included in the study. Among these, 6,537 (27.84%) were patients with HUA alone, 2,015 (8.58%) had HTN alone, and 2,836 (12.08%) had HTN-HUA. The multivariate logistic regression analysis showed that the AIP, LAP, VAI, TyG, BRI, ABSI, and CMI were all significantly associated with concurrent HTN-HUA. The OR for the highest quartile of the seven indexes for HTN-HUA were as follows: AIP was 4.45 (95% CI 3.82-5.18), LAP was 9.52 (95% CI 7.82-11.59), VAI was 4.53 (95% CI 38.9-5.28), TyG was 4.91 (95% CI 4.15-5.80), BRI was 9.08 (95% CI 7.45-11.07), ABSI was 1.71 (95% CI 1.45 -2.02), and CMI was 6.57 (95% CI 5.56-7.76). Notably, LAP and BRI demonstrated significant discriminatory abilities for HTN-HUA, with area under the curve (AUC) values of 0.72 (95% CI 0.71 - 0.73) and 0.73 (95% CI 0.72 - 0.74) respectively. Conclusion: The AIP, LAP, VAI, TyG, BRI, ABSI, and CMI all show significant correlation with HTN-HUA. Notably, both LAP and BRI demonstrate the capability to differentiate cases of HTN-HUA. Among these, BRI is underscored for its effective, non-invasive nature in predicting HTN-HUA, making it a superior choice for early detection and management strategies.

The prevalence of obesity and relationship between obesity indicators and chronic diseases in Northern Shaanxi, China.

INTRODUCTION: Obesity not only affects human health but also is an important risk factor for a variety of chronic diseases. Therefore, it is particularly important to analyse the epidemic trend of obesity and actively carry out the prevention and control of obesity in the population. MATERIAL AND METHODS: A total of 4565 adults were selected by multi-stage stratified random sampling in Shenmu, Shaanxi Province, China. Univariate analysis was used to explore the epidemic characteristics of obesity in this region. Multivariate logistic regression was used to analyse the relationship between obesity and chronic diseases. Finally, the prediction efficiency of different obesity indexes was analysed by drawing receiver operator characteristic curves (ROC). All statistical analysis was completed by SPSS 26.0 software. RESULTS: The prevalence rates of overweight, obesity, and central obesity were 39.9%, 18.2%, and 48.0%, respectively. After adjusting for other confounding factors, multivariate logistic regression analysis showed that overweight and obesity were risk factors for hypertension, dyslipidaemia, and hyperuricaemia. Central obesity is a risk factor for dyslipidaemia and hyperuricaemia. High level of waist-to-height ratio (WHtR) was a risk factor for dyslipidaemia and hyperuricaemia (p < 0.05). Obesity-related indicators: body mass index (BMI), waist circumference (WC), and WHtR, are strongly correlated with the increased risk of chronic diseases in northern Shaanxi, China. The optimal BMI cut-off values for predicting hypertension, dyslipidaemia, and hyperuricaemia were 24.27, 24.04, and 25.54, respectively. The optimal WC cut-off values for predicting dyslipidaemia and hyperuricaemia were 84.5 and 90.5, and WHtR cut-off values were 0.52 and 0.54, respectively. CONCLUSION: The problem of overweight, obesity, and central obesity in adults is serious in northern Shaanxi, China. Obesity of all types will increase the risk of chronic diseases. Therefore, a variety of preventive and therapeutic measures should be adopted to curb obesity and reduce the incidence of related chronic diseases.

Piperine Improves Hyperuricemic Nephropathy by Inhibiting URAT1/GLUT9 and the AKT-mTOR Pathway.

Uncontrolled hyperuricemia often leads to the development of hyperuricemic nephropathy (HN), characterized by excessive inflammation and oxidative stress. Piperine, a cinnamic acid alkaloid, possesses various pharmacological activities, such as antioxidant and anti-inflammatory effects. In this study, we intended to investigate the protective effects of piperine on adenine and potassium oxonate-induced HN mice and a uric-acid-induced injury model in renal tubular epithelial cells (mRTECs). We observed that treatment with piperine for 3 weeks significantly reduced serum uric acid levels and reversed kidney function impairment in mice with HN. Piperine (5 µM) alleviated uric acid-induced damage in mRTECs. Moreover, piperine inhibited transporter expression and dose-dependently inhibited the activity of both transporters. The results revealed that piperine regulated the AKT/mTOR signaling pathway both in vivo and in vitro. Overall, piperine inhibits URAT1/GLUT9 and ameliorates HN by inhibiting the AKT/mTOR pathway, making it a promising candidate for patients with HN.

Robust positive association between serum urate and the risk of chronic obstructive pulmonary disease: hospital-based cohort and Mendelian randomisation study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and hyperuricaemia are both characterised by systemic inflammation. Preventing chronic diseases among the population with common metabolic abnormality is an effective strategy. However, the association of hyperuricaemia with the higher incidence and risk of COPD remains controversial. Therefore, replicated researches in populations with distinct characteristics or demographics are compellingly warranted. METHODS: This cohort study adopted a design of ambispective hospital-based cohort. We used propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) to minimise the effects of potential confounding factors. A Cox regression model and restricted cubic spline (RCS) model were applied further to assess the effect of serum urate on the risk of developing COPD. Finally, we conducted a two-sample Mendelian randomisation (MR) analysis to explore evidence of causal association. RESULTS: There is a higher incidence in the population with hyperuricaemia compared with the population with normal serum urate (22.29/1000 person-years vs 8.89/1000 person-years, p=0.009). This result is robust after performing PSM (p=0.013) and IPTW (p<0.001). The Cox model confirms that hyperuricaemia is associated with higher risk of developing COPD (adjusted HR=3.35 and 95% CI=1.61 to 6.96). Moreover, RCS shows that the risk of developing COPD rapidly increases with the concentration of serum urate when it is higher than the reference (420 µmol/L). Finally, in MR analysis, the inverse variance weighted method evidences that a significant causal effect of serum urate on COPD (OR=1.153, 95% CI=1.034 to 1.289) is likely to be true. The finding of MR is robust in the repeated analysis using different methods and sensitivity analysis. CONCLUSIONS: Our study provides convincing evidence suggesting a robust positive association between serum urate and the risk of developing COPD, and indicates that the population with hyperuricaemia is at high risk of COPD in the Chinese population who seek medical advice or treatment in the hospital.

Causal association study of the dynamic development of the metabolic syndrome based on longitudinal data.

The dynamic progression of metabolic syndrome (MetS) includes developmental deterioration and reverse recovery; however, the key factors in this bidirectional progression have not been identified. Our study aimed to use the data obtained from the China Health and Retirement Longitudinal Study (CHARLS) and construct a Bayesian network to explore the causal relationship between influential factor and the development and recovery of MetS. Followed up at 4 years, forward progression of MetS occurred in 1543 and reverse recovery of MetS occurred in 1319 of 5581 subjects. Bayesian Networks showed that hyperuricemia and body mass index (BMI) levels directly influenced progression of MetS, and gender, exercise and age play an indirect role through hyperuricemia and BMI levels; high hemoglobin A1c (HbA1c) and BMI levels directly influenced recovery of MetS, and gender and exercise play an indirect role through BMI levels. Bayesian Network inference found that the rate of progression of MetS in subjects with hyperuricemia increases from 36 to 60%, the rate of progression of MetS in subjects with overweight or obese increases from 36 to 41% and the rate of reverse recovery rate of MetS in subjects with high HbA1c decreased from 33 to 20%. Therefore, attention to individuals at high risk of hyperuricemia, high HbA1c levels, and overweight/obesity should be enhanced, with early detection and following healthy behavioral interventions to prevent, control and delay the progression of MetS and its components.

Serum uric acid level is associated with glomerular ischemic lesions in patients with primary membranous nephropathy: an analytical, cross-sectional study.

To investigate the relationship between serum uric acid level and glomerular ischemic lesions (GIL) in patients with primary membranous nephropathy (PMN) and identify relevant risk factors. A total of 201 patients with PMN but normal renal function confirmed by renal biopsy executed in the Liaocheng People's Hospital, China, during January 2020-January 2023 were analyzed retrospectively. The enrolled patients were divided into a hyperuricemia group and a normal serum uric acid group (control group) according to their serum uric acid levels. Then, the participants were further divided into a non-GIL group or a GIL group based on the patient's renal biopsy results. The two groups' clinical and pathological data and meaningful indicators for differences were analyzed by binary logistic regression analysis. Additionally, the serum uric acid level prediction value on GIL was investigated using receiver operating characteristic (ROC) curves. Compared with the control group, the hyperuricemia group exhibited high serum uric acid, the prevalence of GIL, serum albumin, the prevalence of hypertension, and low-density lipoprotein cholesterol (LDL) levels (P < 0.05). Compared with the non-GIL group, the GIL group exhibited were older, had enhanced serum uric acid, serum albumin, and an increased prevalence of tubular atrophy/interstitial fibrosis (TA/IF), arteriolosclerosis, and low eGFR levels (P < 0.05). The binary logistic regression analysis revealed that the serum uric acid and the TA/IF are independent risk factors of GIL (P < 0.05). The AUC of ROC of GIL of PMN patients, predicted based on the serum uric acid concentration, was 0.736 (P < 0.05), wherein the threshold = 426.5 µmol/L and the Youden's index = 0.41. Serum uric acid concentration and the TA/IF are independent risk factors of GIL in patients with PMN, and the former exhibits prediction value on GIL in patients with PMN.

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.

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.