Effect Of Serum Uric Acid Research Articles

Elevated Serum Uric Acid Levels Mediate the Associations of Ambient PM2.5 and Its Components with Glaucoma

Limited epidemiological information exists on the relationships between fine particulate matter (PM2.5) components and glaucoma risk. Moreover, the potential mediation effect of serum uric acid (UA) levels remains unexplored. Data from the China Health and Retirement Longitudinal Survey (CHARLS) spanning 2011–2020 were analyzed. Cox proportional hazard models and quantile-based g-computation (qg-computation) models were applied to determine the associations of PM2.5 and its five components (including sulfate [SO₄2⁻], nitrate [NO₃⁻], ammonium [NH₄⁺], organic matter [OM], and black carbon [BC]) with glaucoma risk. A causal mediation model was applied to assess the mediation effect of serum UA. Individual exposure to PM2.5 mass and its five components was positively associated with glaucoma risk, respectively. The mixture of PM2.5 components were significantly and positively associated with glaucoma risk (hazard ratio [HR] = 1.31, 95% confidence interval [CI]: 1.18–1.45), with NH₄⁺ and BC contributing the most (proportions: 81% and 19%, respectively). These associations were modified by sex and residence. Elevated serum UA levels played a mediated role in the association between PM2.5 mass and its five chemical components and glaucoma, with mediated proportions ranging from 12% to 15%. Prolonged exposure to PM2.5 components, especially NH4+ and BC, may elevate the glaucoma risk among Chinese middle-aged and older people, and elevated serum UA levels may play a key mediating role.

Association between neutrophil-percentage-to-albumin ratio (NPAR) and metabolic syndrome risk: insights from a large US population-based study

Metabolic syndrome (MetS) is a cluster of conditions that increase the risk of cardiovascular disease and diabetes. This study aimed to investigate the association between Neutrophil-Percentage-to-Albumin Ratio (NPAR) and MetS in a large, nationally representative US population. We analyzed data from 28,178 participants in the National Health and Nutrition Examination Survey (NHANES) 2005–2018. Logistic regression models were used to evaluate the association between NPAR and MetS. Restricted cubic spline (RCS) models were employed to assess the dose-response relationship. Mediation analyses were conducted to explore potential mediating effects of serum uric acid and triglyceride-glucose (TyG) index. After adjusting for confounders, participants in the highest NPAR quartile had a 14% higher risk of MetS compared to those in the lowest quartile (OR 1.14, 95%CI 1.03–1.27, P = 0.010). RCS models revealed a monotonic increasing trend between NPAR and MetS risk (P for overall association = 0.002). Mediation analyses showed that serum uric acid and TyG index mediated 14.93% and 29.45% of the total effect of NPAR on MetS, respectively. Subgroup analyses indicated that the positive association between NPAR and MetS was more pronounced in Mexican Americans, individuals aged 20–65 years, those with lower income, males, current smokers, and moderate drinkers. Higher NPAR is associated with increased risk of MetS in the US adult population. This association is partially mediated by serum uric acid and TyG index. These findings suggest that NPAR may serve as a novel biomarker for MetS risk assessment and provide insights into potential mechanisms linking inflammation and metabolic disorders.

The relationship between serum uric acid and homocysteine is influenced by kidney function

Background and AimPrior research has established a relationship between homocysteine (Hcy) and serum uric acid (SUA) levels; however, the precise mechanisms underlying this association remain unclear. The objective of this research was to explore the correlation between SUA and Hcy and to evaluate the possible role of kidney function as a mediator in the connection between SUA and Hcy. Methods and ResultsConsecutive enrollment of 16870 participants aged 20-60 years was conducted at the Third Xiangya Hospital of Central South University. Self-reported health questionnaires were used to gather information on health behaviors and medical backgrounds. Trained personnel performed laboratory examinations using standard methods. A mediation analysis was performed to explore the possible effect of renal function on the association between SUA and Hcy levels. Estimated glomerular filtration rate (eGFR) was used to assess kidney function. Logistic regression analysis showed that SUA levels were positively correlated with Hcy levels and hyperhomocysteinemia (HHcy) risk (p<0.01). Subgroup analysis showed the robustness of the results. Significant mediation effects of eGFR were found in the relationship between SUA and Hcy, as demonstrated by the subsequent mediation analysis. In the overall study group, the percentage of eGFR mediated in the association between SUA and Hcy was 63.36%, with 41.59% and 57.59% in women and men, respectively. ConclusionsSUA was positively correlated with Hcy and HHcy risks, and the effects of SUA on Hcy may be mediated by renal function indicators (eGFR).

Shear wave elastography to evaluate the effect of serum uric acid levels on carotid artery elasticity in patients with high-normal blood pressure

Background: Populations with normal high blood pressure often already have elevated blood uric acid levels and a higher chance of developing atherosclerosis, which accelerates the process of cardiovascular disease. The risk of atherosclerosis increases with thickening of the carotid artery intima-media, and changes in carotid artery elasticity precede intima-media changes, so early monitoring of carotid artery elasticity is of great significance in the prevention of cardiovascular disease. Using shear wave elastography (SWE) to evaluate the effect of serum uric acid (SUA) levels on carotid artery elasticity in patients with high-normal blood pressure (BP). Methods: One hundred and fifteen patients with high-normal BP were selected, and then divided into tertiles according to the SUA levels. The left carotid intima-media thickness (IMT), peak systolic velocity (PSV) and diameter of common carotid artery were measured by two-dimensional ultrasound and Doppler flow imaging. Longitudinal elasticity of the left anterior carotid wall was measured by SWE, including the mean values of the minimum elastic modulus (MEmin), maximum elastic modulus (MEmax) and mean elastic modulus (MEmean). Results: IMT, MEmean, MEmin and MEmax were obviously higher in the 3rd tertile (all P &lt; 0.05), while there were no obviously different between the 1st tertile and 2nd tertile. Pearson correlation analysis showed positive correlations between SUA and SWE-related parameters, while there was no correlation with IMT. Multiple linear regression analysis found that age, systolic BP, and SUA levels were independently associated with SWE-related parameters. Conclusion: SWE will be more helpful than IMT in monitoring the effect of blood uric acid levels on carotid artery elasticity in patients with high-normal BP.

Role of uric acid in neurodegenerative diseases, focusing on Alzheimer and Parkinson disease: A new perspective.

Neurodegenerative diseases (NDs) such as Alzheimer disease (AD) and Parkinson disease (PD) are group of diseases affecting the central nervous system (CNS) characterized by progressive neurodegenerations and cognitive impairment. Findings from different studies highlighted the beneficial and detrimental effects of serum uric acid on the development and progression of NDs. Therefore, this mini-review aims to discuss the beneficial and detrimental effects of uric on NDs. The neuroprotective effect of uric acid is mainly related to the antioxidant effect of uric acid which alleviates oxidative stress-induced neurodegeneration in AD and PD. However, long-term effect of hyperuricemia prompts for the development and progression of cognitive impairment. Hyperuricemia is associated with cognitive impairment and dementia, and gout increases dementia risk. In addition, hyperuricemia can cause cerebral vascular injury which is a risk factor for vascular dementia and cognitive impairment. Taken together, the relationship between uric acid and NDs risk remains conflicting. Hence, preclinical and clinical studies are indicated in this regard.

Effect of serum uric acid on the risk of aortic aneurysm and dissection: A mendelian randomization analysis

Aortic aneurysm and dissection (AAD) are severe vascular diseases with high mortality rates. However, the causal relationship between serum uric acid levels and the occurrence of AAD remains a subject of controversy. To address this issue, we conducted a two-sample Mendelian randomization (MR) analysis to investigate whether there is a causal association between these factors. We obtained single-nucleotide polymorphisms (SNPs) data related to serum uric acid levels from the FinnGen study and data on AAD from the UK Biobank. Various two-sample MR methods, including inverse variance weighted (IVW) analysis, MR-Egger regression analysis, weighted median analysis, and contamination mixture method, were employed to assess the causal relationship between serum uric acid and the risk of AAD. Sensitivity analysis was conducted to evaluate the stability and reliability of the results. The findings revealed a positive association between serum uric acid levels and the risk of aortic aneurysm (AA) (odds ratio [OR] = 1.200, 95 % confidence interval [CI]: 1.020–1.400, P = 0.0239). However, no significant correlation was observed between serum uric acid levels and the occurrence of aortic dissection (AD) (OR = 0.893, 95 % CI = 0.602–1.326, P = 0.576). Our study, which employed MR analysis, identified a positive association between serum uric acid levels and the risk of AA. However, we did not observe a significant correlation with AD.

Uric Acid Inhibits Mice Pancreatic Steatosis via the Glycerophospholipid Pathway.

Background: despite evidence for mutually reinforcing effects of serum uric acid (SUA) and lipids, the effects of uric levels on pancreatic steatosis are not well-established. In this study, the relationship between low concentrations of uric acid and pancreatic steatosis was evaluated. Methods: forty C57BL/6J mice were fed a diet of high uric acid (HU), high fat (HF), high uric acid and high fat (HUHF), and normal control (NC) (10 mice in each group). Weight was measured weekly. Ultrasonography was performed to observe the pancreatic echo intensity of all mice before the end of feeding. Subsequently, peripheral blood was taken for biochemical examination. Intact pancreatic tissues were taken, part of which was used for pathological examination, part of which was used for PCR experiments and Western Blot experiments to obtain glycerophospholipid-associated mRNA data and protein levels. Results: body weight was significantly higher in the HF group than in the other three groups. Higher uric acid matched lower total cholesterol and triglyceride, matched higher low-density lipoprotein, and matched equal high-density lipoprotein. Ultrasound images and HE staining of pancreatic tissues of mice showed that higher uric acid matched lower fat content. The mRNA levels of phospholipase A2 group IB were highest in high uric acid group, while relative protein expression levels were lowest in high uric acid and control groups. Phospholipase A2 group IIA showed the opposite patterns. Conclusions: elevated serum uric acid at low concentrations can inhibit pancreatic steatosis, which is modulated via the glycerophospholipid metabolic pathway.

Associations of urinary zinc exposure with blood lipid profiles and dyslipidemia: Mediating effect of serum uric acid

The relationship between zinc (Zn) exposure and abnormal blood lipids including dyslipidemia is contentious. Serum uric acid (SUA) has been reported to be correlated to both Zn exposure and dyslipidemia. The underlying mechanisms of Zn exposure associated with blood lipids and the mediating effects of SUA remain unclear. Therefore, this study analyzed the data from Chinese 2110 adults (mean age: 59.0 years old) in rural areas across China to explore the associations of Zn exposure with blood lipid profiles and dyslipidemia, and to further estimate the mediating effects of SUA in these relationships. The study data showed that urinary Zn was associated with increased levels of blood lipid components triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C). Moreover, an increased risk of dyslipidemia was observed in the study participants who had higher urinary Zn levels. Compared with the first quartile, the fourth quartile of urinary Zn concentration corresponded to the increase of TG (β = 0.20, 95 % CI: 0.12, 0.28), LDL-C (β = 0.06, 95 % CI: 0.01, 0.10) and dyslipidemia risk (OR = 2.16, 95 % CI: 1.50, 3.10), respectively. Elevated urinary Zn was also associated with higher levels of SUA and hyperuricemia risk. The SUA levels were positively related to total cholesterol (TC), TG, LDL-C levels and dyslipidemia risk. Mediation analyses revealed that SUA mediated 31.75 %, 46.16 % and 19.25 % of the associations of urinary Zn with TG, LDL-C levels and dyslipidemia risk, respectively. The subgroup and sensitivity analyses confirmed the positive associations between urinary Zn and blood lipid profiles and the mediating effect of SUA. The national population-based study further enhanced our understanding of the associations between Zn exposure and blood lipid profiles and mediating effect of SUA among generally healthy, middle-aged, and elderly individuals.

Long-term effects of PM2.5 constituents on metabolic syndrome and mediation effects of serum uric acid

Exposure to particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5) was associated with the risk for metabolic syndrome (MetS) in the general population, but the contributions of individual PM2.5 constituents to this association and the potential pathway between PM2.5 constituents and MetS risk are not well elaborated. This study aimed to investigate associations between PM2.5 constituents and MetS in general populations, relative importance of PM2.5 constituents to and mediation effects of serum uric acid (SUA) on those associations. The 48,148 participants from a provincially representative cohort established in southwest China were included. The 3-year average concentrations of PM2.5 and its constituents (nitrate [NO3−], sulfate [SO42−], ammonium [NH4+], organic matter [OM], and black carbon [BC]) were estimated using a series of machine-learning models. Multivariate logistic regression and weighted quantile sum regression were used to estimate effects of independent PM2.5 constituents on MetS and their contributions to the joint effect. Mediation analysis examined the potential mediation effects of SUA on the associations between PM2.5 constituents and MetS. Each interquartile range (IQR) increase in the concentration of PM2.5 constituents was all positively associated with the increased MetS odds, including SO42− (OR = 1.15 [1.11, 1.19]]), NO3− (OR = 1.12 [1.08, 1.16]), NH4+ (OR = 1.13 [1.09, 1.17]), OM (OR = 1.09 [1.06, 1.13]), and BC (OR = 1.09 [1.06, 1.13]). Their joint associations on MetS were mainly attributed to SO42− (weight=46.1%) and NH4+ (44.0%). The associations of PM2.5 constituents with abnormal MetS components were mainly attributed to NH4+ for elevated BP (51.6%) and reduced HDL-C (97.0%), SO42− for elevated FG (68.9%), NO3- for elevated TG (51.0%), and OM for elevated WC (63.0%). Percentages mediated by SUA for the associations of PM2.5, SO42−, NO3−, and BC with MetS were 13.6%, 13.1%, 10.6%, and 11.1%, respectively. Long-term exposure to PM2.5 constituents, mainly NH4+ and SO42−, was positively associated with MetS odds, partially mediated by SUA.

Effect of serum uric acid and gout on the incidence of colorectal cancer: A meta-analysis

ObjectivePathogenesis of colorectal cancer (CRC) depends on multiple factors. Identifying risk factors for CRC may facilitate the early prevention of the disease. We aimed to assess whether existing evidence suggests that serum uric acid (SUA) levels and gout are associated with CRC incidence. MethodsThe study was registered on PROSPERO (CRD42022371591). Searches of PubMed, Embase, and Cochrane Library were conducted from the establishment to November 11, 2022. Pooled relative risk (RR) with 95 % confidence intervals (CI) was derived to evaluate the effect of SUA or gout on CRC incidence. Non-linear trend analysis was conducted to explore the relationship between SUA level and CRC incidence. ResultsTwelve eligible studies with 22 reports were included. A meta-analysis of the included studies showed that when the highest and lowest SUA level categories were compared, an association between SUA level and CRC incidence was revealed (RR, 1.35; 95 % CI: 1.27–1.43; P < 0.001). Non-linear relationship between SUA level and CRC incidence was found. Further meta-analysis indicated that gout was associated with CRC incidence (RR, 1.22; 95 % CI: 1.08–1.36; P = 0.001). ConclusionsBoth SUA level and gout were associated with an increased risk of CRC. Maintaining low SUA levels may be beneficial in reducing the incidence of CRC. Further studies evaluating the precise mechanisms underlying this association are needed to establish whether SUA/gout causes CRC.

#5619 THE ASSOCIATION BETWEEN THE LEVELS OF URIC ACID AND RENAL OUTCOMES IN EARLY CKD PATIENTS: A MULTI-CENTER REAL-WORLD DATA ANALYSIS

Abstract Background and Aims It is well known that serum uric acid (SUA) plays an important role both in patients with and without chronic kidney disease (CKD). However, the effect of SUA on renal outcomes of CKD patients, especially with asymptomatic hyperuricemia, remains controversial. Therefore, our study explores the relationship between SUA and adverse events in early CKD (stage 1-3) patients in a real-world setting. Method This multi-center real-world study analyzed the data from Chinese Renal Data System (CRDS). Eligible CKD patients (eGFR) (estimated glomerular filtration rate≥30 mL/min/1.73 m2) were enrolled. The primary endpoint is the decline of renal function defined as at least 40% decrease in eGFR. The secondary endpoints include onset of composite cardiovascular events and all-cause mortality. A multivariable cox regression model were used and the associations between levels of mean SUA and all endpoints were evaluated on a continuous scale with restricted cubic spline (RCS) curves based on Cox proportional hazards models. Kaplan-Meier survival curves were used to illustrate the ability of SUA to predict the end points. Results 25,202 adults (mean [SD] age, 52.59 [17.90] years, 8,212 male [46.1%], 9,604 female [53.9%]) were included in this study. During a median follow-up period of 2.61 years, 3,451 (15.9%) at least 40% decreased in eGFR. After adjustment for confounders, higher uric acid concentrations were independently associated with the higher risk for the decline of renal function [Per SD increment adjusted hazard ratio [aHR]: 1.41, 95%CI 1.36-1.47]; composite cardiovascular events [Per SD increment [aHR]: 1.04, 95%CI 1.01-1.07], all-cause mortality [Per SD increment [aHR]:1.32, 95%CI 1.14-1.54]. RCS curves showed that HRs for renal function progression, all-cause mortality and composite cardiovascular events increased significantly with the increase of SUA concentration in CKD patients. Results were consistent in stratified analyses. The KM curves suggested that patients with asymptomatic hyperuricemia had a substantially worse survival rate for renal function. Conclusion SUA is an independent risk factor for the decline of renal function, cardiovascular events and all-cause mortality in early CKD patients (stage 1-3). Treatment of asymptomatic hyperuricemia may be a potential avenue to improve outcomes in CKD patients.

The effects of cardiometabolic factors on the association between serum uric acid and risk of all-cause mortality in adults with congestive heart failure

ABSTRACT Background Serum uric acid (SUA) has been shown to increase all-cause mortality from cardiovascular disease. However, limited studies have examined the mediating effect of dyslipidemia, hyperglycemia, or hypertension on the association between SUA and all-cause mortality in patients with congestive heart failure (CHF). Methods Participants in the present investigation were 620 US adults with CHF from the NHANES database (1999–2014). The relationship between SUA and all-cause mortality was evaluated utilizing multivariable Cox proportional hazards models. Additionally, the nonlinearity between SUA and mortality was investigated utilizing Restricted Cubic Splines (RCS) and 2-piecewise Cox proportional hazards models. Finally, the mediating role of cardiometabolic factors on the relationship between SUA and all-cause mortality was investigated utilizing the mediation analysis. Results During a mean follow-up of 7.6 years, 391 (63.1%) all-cause deaths occurred. Furthermore, we found a U-shaped association between SUA and all-cause mortality. The inflection point for the RCS curve was found at a SUA level of 363 umol/L. The hazard ratios (95% confidence intervals) for all-cause mortality were 0.998 (0.995–1.000) and 1.003 (1.002–1.005) to the left and right of the inflection point, respectively. This U-shaped association was also observed in both subgroups of sex and age. Moreover, the effect of SUA on all-cause mortality was not mediated by hypertension, hyperglycemia, or dyslipidemia (all P-values>0.05). Conclusion The association between SUA level and all-cause mortality followed a U-shaped curve, and this association was not mediated by hypertension, hyperglycemia, or dyslipidemia.

Association of serum uric acid and fasting plasma glucose with cognitive function: a cross-sectional study

BackgroundThe combined effect of serum uric acid (SUA) and blood glucose on cognition has not been explored. This study aimed to examine the separate and combined association of SUA and fasting plasma glucose (FPG) or diabetes mellitus (DM) with cognition in a sample of Chinese middle-aged and elderly population.MethodsA total of 6,509 participants aged 45 years or older who participated in the China Health and Retirement Longitudinal Study (CHARLS, 2011) were included. The three cognitive domains assessed were episodic memory, mental status, and global cognition (the sum of the first two terms). Higher scores indicated better cognition. SUA and FPG were measured. The participants were grouped based on SUA and FPG quartiles to evaluate their combined associations of cognition with SUA Q1–Q3 only (Low SUA), with FPG Q4 only (High FPG), without low SUA and high FPG levels (Non), and with low SUA and high FPG levels (Both), multivariate linear regression models were used to analyze their association.ResultsLower SUA quartiles were associated with poorer performance in global cognition and episodic memory compared with the highest quartile. Although no association was found between FPG or DM and cognition, high FPG or DM combined with low SUA levels in women (βFPG = -0.983, 95% CI: -1.563–-0.402; βDM = -0.800, 95% CI: -1.369–-0.232) had poorer cognition than those with low SUA level only (βFPG = -0.469, 95% CI: -0.926–-0.013; βDM = -0.667, 95% CI: -1.060–-0.275).ConclusionMaintaining an appropriate level of SUA may be important to prevent cognitive impairment in women with high FPG.

Synergistic effect of serum uric acid and body mass index trajectories during middle to late childhood on elevation of liver enzymes in early adolescence: Findings from the Ewha Birth and Growth Study.

We aimed to determine whether serum uric acid (SUA) and body mass index (BMI) trajectories in childhood have longitudinal association with liver enzymes in adolescence. We conducted a study using data from the Ewha Birth and Growth Cohort. Individual trajectories of SUA (n = 203) and BMI (n = 206) from 5, 7, and 9 years were defined by group-based trajectory modeling. Also, liver function enzymes were collected at 11 to 12 year of age (Aspartate Aminotransferase [AST], Alanine transaminase [ALT], and Gamma-glutamyl transferase [γ-GTP]) (n = 206). Using a generalized linear model, the effects of SUA trajectory and BMI trajectory on liver function enzymes were assessed. We also assessed the interaction effect of SUA and BMI trajectories on liver enzymes. For trajectory patterns, both SUA and BMI were classified into two distinct groups (High or Low). Both trajectory of SUA and BMI in childhood were positively associated with levels of liver enzymes at 11-12 years of age. The results showed that the combined effect of SUA and BMI trajectories on liver enzymes had a higher means in high-risk group (high SUA-high BMI trajectories group) than in low-risk group (low SUA-low BMI trajectories group) for ALT and γ-GTP, respectively. It remained significant association when adjusted for covariates. In addition, the interaction of BMI and SUA trajectories showed a significant synergistic effect. Elevated childhood SUA and BMI trajectories are associated with increased liver enzymes in beginning of adolescent. This finding suggesting that early interventions in SUA and BMI may need for optimization of liver enzymes as potential marker for development of related disease in later life.

Association between serum uric acid levels and clinical outcomes in patients with acute kidney injury

Background The effects of serum uric acid (SUA) on clinical outcomes in patients with acute kidney injury (AKI) are unclear. The aim of this study was to investigate the association of SUA levels with clinical outcomes of AKI patients. Methods The data of AKI patients hospitalized in the Affiliated Hospital of Qingdao University were retrospectively reviewed. Multivariable logistic regression was utilized to assess the association between SUA levels and the clinical outcomes of AKI patients. Receiver operating characteristic (ROC) analysis was applied to assess the predictive ability of SUA levels for in-hospital mortality in patients with AKI. Results A total of 4,646 AKI patients were eligible for study inclusion. In multivariable analysis, after adjustment for various confounding factors in the fully adjusted model, a higher SUA level was found to be associated with increased in-hospital mortality of AKI patients with an odds ratio (OR) of 1.72 (95% CI, 1.21–2.33, p = 0.005) for the SUA level >5.1–6.9 mg/dl group and 2.75 (95% CI, 1.78–4.26, p < 0.001) for the SUA level >6.9 mg/dl group compared with the reference group (SUA ≤3.6 mg/dl). In the ROC analysis, the area under the curve (AUC) of SUA was 0.65 with a sensitivity of 51% and a specificity of 73%. Conclusions An elevated SUA level is associated with an increased risk of in-hospital mortality in patients with AKI, and it appears to be an independent prognostic marker for these patients.

The effect of serum uric acid, bilirubin and albumin levels on antioxidant status in HIV-negative immunocompetent cryptococcal meningitis patients with post-infectious inflammatory response syndrome.

Oxidative imbalances have been observed in various neurological diseases. Despite the microbiological control in cryptococcal meningitis (CM), a proportion of previously healthy patients experience a clinical deterioration known as post-infectious inflammatory response syndrome (PIIRS). However, the antioxidant status in PIIRS remains unclear. In this study, we found that the serum antioxidant status of HIV-negative immunocompetent CM patients during PIIRS episodes was lower than that of healthy controls. There was a relationship between baseline serum indirect bilirubin levels and the development of PIIRS, and serum uric acid levels may indicate the severity of the disease during PIIRS episodes. Oxidative stress may play a role in the development of PIIRS.

Prothrombotic Effect of Serum Uric Acid in Hypertensive Patients

Prothrombotic Effect of Serum Uric Acid in Hypertensive Patients

Interactive effect of serum uric acid and handgrip strength on all-cause mortality among Japanese community-dwelling people

BackgroundUric acid is both a pro-oxidant and an antioxidant. This study examined whether serum uric acid (SUA) is associated with all-cause mortality and cardiovascular biomarkers in members of the general population who had varying levels of handgrip strength (HGS). MethodsThe analysis is based on 1736 participants, of whom 785 were male (69 ± 11 years old) and 951 were female (69 ± 9 years old). We obtained adjusted relative risk estimates for all-cause mortality from the Japanese Basic Resident Registry and used a Cox proportional hazards model (adjusted for possible confounders) to determine the hazard ratios (HR) and 95% confidence intervals (CI). ResultsThe results indicated a significant interaction between the effects of SUA levels and HGS on all-cause mortality risk. Among participants with low HGS (<30.0 kg in males, <20.0 kg in females), low SUA levels (<3.5 mg/dL in males, <3.0 mg/dL in females; HR: 2.40; 95% CI: 1.07–5.40) and high SUA levels (≥8.0 mg/dL in males, ≥7.0 mg/dL in females; HR: 3.05; 95% CI: 1.41–6.59) were associated with a significantly higher HR for all-cause mortality than medium SUA levels (3.5–7.9 mg/dL in males, 3.0–6.9 mg/dL in females). Among participants with high HGS (≥30.0 kg in males; ≥20.0 kg in females), there was no difference between the HR for all-cause mortality between the three SUA-category groups. ConclusionsThe association between SUA and the risk of all-cause mortality was U-shaped for this population of community-dwelling adults. This was primarily true for those with low HGS.

Association between serum uric acid level and systemic lupus erythematosus kidney outcome: An observational study in Southern Chinese population and a meta-analysis.

The study aimed to explore the effect of serum uric acid (SUA) level on the progression of kidney function in systemic lupus erythematosus (SLE) patients. A total of 123 biopsy-proven lupus nephritis (LN) patients were included in this retrospective observational study. Cox proportional hazard regression analyses as well as restricted cubic spline analyses were performed to identify predictors of renal outcome in LN patients. We also performed a systematic review and meta-analysis for SUA and overall kidney outcomes in SLE patients. Based on the laboratory tests at renal biopsy, 72 (58.5%) of the 123 patients had hyperuricemia. The median (IQR) follow-up duration was 3.67years (1.79-6.63years), and a total of 110 (89.4%) patients experienced progression of LN. Increased serum uric acid level, whether analyzed as continuous or categorical variable, was associated with higher risk of LN progression in Cox proportional hazard regression model (hazard ratio [HR]: 1.003, 95% confidence interval [CI]: 1.001-1.005; HR: 1.780, 95% CI: 1.201-2.639, respectively). This relationship maintained in women (HR: 1.947, 95% CI: 1.234-3.074) but not men (HR: 2.189, 95% CI: 0.802-5.977). The meta-analysis showed a similar result that both continuous and categorical SUA were positively associated with the risk of kidney function progression in LN (weighted mean difference [WMD]: 1.73, 95% CI: 0.97-2.49; odds ratio [OR]: 1.55, 95% CI: 1.20-2.01, respectively). Our study found overall and especially in women that higher SUA in LN patients were associated with increased risk of renal progression. Meta-analysis yielded consistent results. Future studies are required to establish if uric acid can be used as a biomarker for risk assessment and/or as a novel therapeutic target in SLE.

Uric acid and arterial stiffness in children and adolescents: Role of insulin resistance and blood pressure.

Several studies describe the association between serum uric acid (SUA) and arterial stiffness in adults. Uric acid contributes through several mechanisms to the increase in blood pressure (BP) and adversely affects the insulin signaling pathway. Moreover, SUA predict the development of hypertension and insulin resistance up to type 2 diabetes. Early arterial stiffening, estimated by carotid-femoral pulse wave velocity (PWV), may already be present in pediatric age. Aim of our study was to investigate the relationship between SUA and PWV in a pediatric population and its interaction with insulin resistance and BP. In 322 children and adolescents (56.2% male, mean age 11.3 [SD 2.8] years), we measured weight, height, waist circumference, BP and PWV. We also assayed SUA and estimated glomerular filtration rate (eGFR) and calculated HOMA-index as a marker of insulin resistance. Simple and multiple regression analyses were performed to assess variables associated with PWV. Mediation models were applied to identify the direct and indirect effects of individual variables on PWV. On univariate analysis, age (p < 0.001), waist circumference-to-height ratio (p = 0.036), systolic and diastolic BP (SBP and DBP) z-score (p < 0.001), heart rate (p = 0.028), SUA (p = 0.002), HOMA-index (p < 0.001), and eGFR (p = 0.014) were significantly associated with PWV. The multiple regression model showed that only age (p = 0.028), SBP z-score (p = 0.006), and heart rate (p = 0.001) were significantly associated with PWV. The results were superimposable when the DBP z-score replaced the SBP z-score in the model. Mediation models showed that the effect of eGFR on PWV was fully mediated by SUA (p = 0.015) and that the effect of SUA on PWV was totally mediated by HOMA-index (p < 0.001). Both SUA (p < 0.01) and HOMA-index (p < 0.01) had a significant association with higher SBP (DBP) z-scores. The double mediation model including both BP and HOMA-index showed that the SUA effect on PWV was totally mediated by both variables (p = 0.005, for HOMA-index, p = 0.004, for SBP z-score and p = 0.007, for combined effect). The results were superimposable when the DBP z-score replaced the SBP z-score in the model. In conclusion, insulin resistance and BP are both important mediators of the association between SUA and vascular stiffness in pediatric age.