Development Of Hyperuricemia Research Articles

Pediatrics hyperuricemia in clinical practice: A retrospective analysis in 1753 children and adolescents with hyperuricemia

ObjectivesSerum levels of uric acid (S-UA) are influenced by the interaction of genetic and environmental factors; detailed studies of hyperuricemia in children are rare. This retrospective study aimed to analyze the causes, risk factors, and therapeutic approaches associated with the development of hyperuricemia in childhood. MethodsIn a single-center study, serum uric acid levels were analyzed in 33,900 samples from 13,890 children and adolescents˂19 years (6760 girls and 7130 boys) obtained between 2013 and 2023. Hyperuricemia was defined as S-UA>370μmol/L (6.22mg/dL) in girls and>420μmol/L (7.06mg/dL) in boys; mild hyperuricemia was defined as 370–420μmol/L in boys˂13 years. ResultsIn the analyzed group, hyperuricemia was found in 1753 patients (12.6%), including 586 girls and 864 boys; mild hyperuricemia was found in 303 boys˂13 years. The most common associated conditions were obesity with body mass index>95th percentile (27.8% of girls, 26.3% of boys) and chronic kidney disease (18.6% of boys, 11.4% of girls). Hyperuricemia was also relatively common in children with connective tissue disorders (10.6%) or different inherited metabolic disorders (10.7%). Transitory hyperuricemia was found in 19.1% of girls and 10.1% of boys with acute gastroenteritis. Urate-lowering therapy was used in 73 children and adolescents with severe hyperuricemia (S-UA 556±107μmol/L, fraction excretion of UA 3.27±1.98%). Eight treated children had chronic kidney disease, nine were extremely obese, one had combined antiepileptic therapy, and 55 had inherited metabolic diseases, including 26 children with disorders of purine metabolism. The initial daily dose of allopurinol (50–100mg) normalized the S-UA (350±80μmol/L) in a majority of children, except for extremely obese adolescents (weight 98–149kg) where the dose had to be increased to 200–300mg. ConclusionsAsymptomatic hyperuricemia is a relatively common biochemical finding in pediatric clinical practice. The etiology of hyperuricemia should be carefully analyzed, and the value of individualized hyperuricemia management and the eventual benefits of urate-lowering therapy in children must be carefully considered.

Associations of Bisphenols Exposure and Hyperuricemia Based on Human Investigation and Animal Experiments.

Hyperuricemia is characterized by elevated blood uric acid (UA) levels, which can lead to certain diseases. Epidemiological studies have explored the association between environmental contaminant exposure and hyperuricemia. However, few studies have investigated the role of chemical exposure in the development of hyperuricemia. Here, we sought to investigate the effects of bisphenol exposure on the occurrence of hyperuricemia. Fifteen bisphenol chemicals (BPs) were detected in human serum and urine samples collected from an area with a high incidence of hyperuricemia in China. Serum UA levels positively correlated with urinary bisphenol S (BPS), urinary bisphenol P (BPP), and serum bisphenol F (BPF). The effects of these three chemicals on UA levels in mice were explored at various exposure concentrations. An increase in serum UA levels was observed in BPS- and BPP-exposed mice. The results showed that BPS exposure increased serum UA levels by damaging the structure of the kidneys, whereas BPP exposure increased serum UA levels by disturbing purine metabolism in the liver. Moreover, BPF did not induce an increase in serum UA levels owing to the inhibition of guanine conversion to UA. In summary, we provide evidence of the mechanisms whereby exposure to three BPs disturbs UA homeostasis. These findings provide new insights into the risks of exposure to bisphenol chemicals.

Using deep learning and molecular dynamics simulations to unravel the regulation mechanism of peptides as noncompetitive inhibitorof xanthine oxidase.

Xanthine oxidase (XO) is a crucial enzyme in the development of hyperuricemia and gout. This study focuses on LWM and ALPM, two food-derived inhibitors of XO. We used molecular docking to obtain three systems and then conducted 200ns molecular dynamics simulations for the Apo, LWM, and ALPM systems. The results reveal a stronger binding affinity of the LWM peptide to XO, potentially due to increased hydrogen bond formation. Notable changes were observed in the XO tunnel upon inhibitor binding, particularly with LWM, which showed a thinner, longer, and more twisted configuration compared to ALPM. The study highlights the importance of residue F914 in the allosteric pathway. Methodologically, we utilized the perturbed response scan (PRS) based on Python, enhancing tools for MD analysis. These findings deepen our understanding of food-derived anti-XO inhibitors and could inform the development of food-based therapeutics for reducing uric acid levels with minimal side effects.

Dyslipidemia and hyperuricemia: a cross-sectional study of residents in Wuhu, China

BackgroundWhile dyslipidemia has been recognized as a potential risk factor for hyperuricemia, there is currently a dearth of large-scale data specifically focused on studying the relationship between these two conditions. To address this gap, the present study analyzed a dataset of 298,891 physical examination records to investigate in greater detail the clinical classification and compositional relationship between hyperuricemia and dyslipidemia.MethodsFor this investigation, a cross-sectional research design was utilized to analyze physical examination data that was gathered from Yijishan Hospital in Wuhu, China between 2011 and 2016. Logistic regression was employed to examine the association between hyperuricemia and dyslipidemia. Furthermore, the association between hyperuricemia and dyslipidemia was evaluated based on the clinical classifications of dyslipidemia and its components.ResultsA total of 298,891 participants from China (124,886 [41.8%] females) were included in the study, with an age range of 18 to 90 years (mean [SD]: 47.76 [13.54] years). In multivariate analysis, the odds of hyperuricemia was 1.878 times higher in patients with dyslipidemia compared to those without dyslipidemia (95% confidence interval [CI]: 1.835–1.922). In the clinical classification of dyslipidemia, individuals with hypertriglyceridemia and mixed hyperlipidemia had 1.753 times (95% CI: 1.706–1.802) and 1.925 times (95% CI: 1.870–1.982) higher odds of hyperuricemia, respectively, compared to those without dyslipidemia. Among the components of dyslipidemia, the odds ratios for hyperuricemia in individuals in the fourth quartile compared to those in the first quartile were 3.744 (95% CI: 3.636–3.918) for triglycerides, 1.518 (95% CI: 1.471–1.565) for total cholesterol, and 1.775 (95% CI: 1.718 − 1.833) for non-high-density lipoprotein cholesterol.ConclusionsDyslipidemia has been independently linked with hyperuricemia. Moreover, the elevation of triglycerides or total cholesterol levels, including conditions such as hypertriglyceridemia and mixed hyperlipidemia, have been observed to have a positive association with the development of hyperuricemia.

A combination of red and processed meat intake and polygenic risk score influences the incidence of hyperuricemia in middle-aged Korean adults.

The high consumption of purine-rich meat is associated with hyperuricemia. However, there is limited evidence linking the consumption of red and processed meat to the genetic risk of hyperuricemia. We investigated the relationship between various combinations of red and processed meat consumption and the polygenic risk scores (PRSs) and the incidence of hyperuricemia in middle-aged Koreans. We analyzed the data from 44,053 participants aged ≥40 years sourced from the Health Examinees (HEXA) cohort of the Korean Genome and Epidemiology Study (KoGES). Information regarding red and processed meat intake was obtained using a semiquantitative food frequency questionnaire (SQ-FFQ). We identified 69 independent single-nucleotide polymorphisms (SNPs) at uric acid-related loci using genome-wide association studies (GWASs) and clumping analyses. The individual PRS, which is the weighted sum of the effect size of each allele at the SNP, was calculated. We used multivariable Cox proportional hazards models adjusted for covariates to determine the relationship between red and processed meat intake and the PRS in the incidence of hyperuricemia. During an average follow-up period of 5 years, 2,556 patients with hyperuricemia were identified. For both men and women, the group with the highest red and processed meat intake and the highest PRS was positively associated with the development of hyperuricemia when compared with the group with the lowest red and processed meat intake and the lowest PRS (hazard ratio [HR], 2.72; 95% confidence interval [CI], 2.10-3.53; P < 0.0001; HR, 3.28; 95% CI, 2.45-4.40; P < 0.0001). Individuals at a high genetic risk for uric acid levels should moderate their consumption of red and processed meat to prevent hyperuricemia.

Commensal Enterococcus faecalis W5 ameliorates hyperuricemia and maintains the epithelial barrier in a hyperuricemia mouse model.

The intestine is responsible for approximately one-third of uric acid (UA) excretion. The effect of commensal Enterococcus faecalis (E. faecalis), one of the most colonized bacteria in the gut, on UA excretion in the intestine remains to be investigated. The aim of this study was to evaluate the effect of commensal E. faecalis on UA metabolism and gut microbiota. The 16SrRNA gene sequencing was used to examine the species of Enterococcus in mouse fecal content. E. faecalis strain was isolated from mouse feces and identified to be E. faecalis W5. The hyperuricemia (HUA) animal model was established with yeast-rich forage and 250 mg·kg-1 ·day-1 potassium oxonate. Oral administration of E. faecalis W5 was given for 20 days, serving as the Efa group. Disrupted intestinal barrier, activated proinflammatory response and low UA excretion in the intestine were found in HUA mice. After E. faecalis W5 treatment, the gut barrier was restored and serum UA level was decreased. Additionally, fecal and intestinal UA levels were elevated, intestinal urate transporter ABCG2 and purine metabolism were upregulated. Moreover, short-chain fatty acid levels were increased, and intestinal inflammation was ameliorated. Commensal E. faecalis W5 ameliorated HUA through reversing the impaired gut barrier, promoting intestinal UA secretion by regulating ABCG2 expression, and decreasing intestinal UA synthesis by regulating purine metabolism. The results may provide the potential for developing treatments for HUA through the intestine.

Exploring the Relationship Between Different Obesity Metabolism Indices and Hyperuricemia in Patients with Hypertension and Coronary Heart Disease.

Previous studies have established a strong association between obesity, high metabolism, and the development of hyperuricemia. However, the relationship between obesity metabolism indices and hyperuricemia in high-risk patients with hypertension and coronary heart disease (CHD) remains unclear. The purpose of this study was to investigate this relationship in patients with both hypertension and CHD, and to identify the obesity metabolism index with the best diagnostic value. A two-center study encompassed 6344 participants with hypertension and CHD. Multiple logistic regression was utilized to examine the correlation between six obesity metabolism indices and hyperuricemia, with restricted cubic spline (RCS) analysis to identify non-linear relationships. Diagnostic value was assessed via receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Multivariable logistic regression revealed a significant correlation between increased obesity metabolism indices and hyperuricemia. Furthermore, RCS analysis revealed a nonlinear dose-response relationship (P for nonlinear < 0.001). Moreover, ROC and DCA results showed that METS-VF index, which combined visceral obesity and metabolic parameters, became the most reliable diagnostic tool. The study underscores a strong association between elevated obesity metabolism indices and hyperuricemia in patients with hypertension and CHD. The METS-VF index, amalgamating visceral obesity and metabolic parameters, emerged as the most reliable diagnostic tool.

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-1β 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.

Target Screen of Anti-Hyperuricemia Compounds from Cortex Fraxini In Vivo Based on ABCG2 and Bioaffinity Ultrafiltration Mass Spectrometry

The ATP-binding cassette (ABC) transporter ABCG2 is a significant urate transporter with a high capacity, and it plays a crucial role in the development of hyperuricemia and gout. Therefore, it has the potential to be targeted for therapeutic interventions. Cortex Fraxini, a traditional Chinese medicine (TCM), has been found to possess anti-hyperuricemia properties. However, the specific constituents of Cortex Fraxini responsible for this effect are still unknown, particularly the compound that is responsible for reducing uric acid levels in vivo. In this study, we propose a target screening protocol utilizing bio-affinity ultrafiltration mass spectrometry (BA-UF-MS) to expediently ascertain ABCG2 ligands from the plasma of rats administered with Cortex Fraxini. Our screening protocol successfully identified fraxin as a potential ligand that interacts with ABCG2 when it functions as the target protein. Subsequent investigations substantiated fraxin as an activated ligand of ABCG2. These findings imply that fraxin exhibits promise as a drug candidate for the treatment of hyperuricemia. Furthermore, the utilization of BA-UF-MS demonstrates its efficacy as a valuable methodology for identifying hit compounds that exhibit binding affinity towards ABCG2 within TCMs.

Uric acid as a predictor of the development of non-alcoholic fatty liver disease in patients with arterial hypertension

Introduction. Currently, increased uric acid (UA) levels are considered an independent risk factor for the development of non-alcoholic fatty liver disease. Oxidative stress, chronic systemic inflammation, and insulin resistance characteristic of non-alcoholic fatty liver disease (NAFLD) may represent possible mechanisms for the association between the development of hyperuricemia and NAFLD.Aim. To clarify the meaning and nature of the relationship between an increase in the level of UA concentration and the development of NAFLD, as well as to evaluate the relationship between uric acid and the risk of cardiovascular complications in patients with hypertension and NAFLD.Materials and methods. A cross-sectional comparative study was conducted, which involved 120 patients aged from 45 to 65 with hypertension of 1–2 degrees, 1–2 stages (with and without NAFLD (FLI &gt; 60). During the examination, a clinical examination was carried out: analysis of anamnesis data, anthropometry. Lipids and uric acid in blood plasma were also analyzed.Results. In the group of comorbid patients, there were significantly more patients with excess of the reference values of UA levels in the blood plasma (OR = 2.25: 95% CI 1.08–4.71). ROC analysis showed that with an uric acid level of 369.5 µmol/l, a high risk of developing NAFLD is predicted. The UA/Cr index in patients with hypertension and NAFLD was statistically significantly higher than in patients in the control group. Increase in the MK/Kr index by 1 USD increases the chances of developing NAFLD by 1.54 times (95% CI: 1.11–2.13). Also, an increase in the concentration of sUA level by 1 µmol/l increases the chances of an increase in the 10-year risk of cardiovascular events to 5.0% or more by 0.6%.Conclusions. With an uric acid level of 369.5 µmol/l, a high risk of developing NAFLD in the study group is predicted. Increase in UA/creatinine index by 1 USD increases the chances of developing NAFLD by 1.54 times. In addition, an increase in the concentration of sUA in the blood plasma by 1 µmol/l increases the chances of an increase in the 10-year risk of cardiovascular events to 5.0% or more by 0.6% in patients with hypertension and NAFLD.

Leukocyte telomere length independently predicts hyperuricemia risk in a longitudinal study of the Chinese population

Background and aimsLeukocyte telomere length (LTL) has been correlated with uric acid levels, although results are inconsistent, and prospective studies are lacking. In this longitudinal, prospective cohort study, we aimed to assess whether a shorter LTL predicts the risk of hyperuricemia. Methods and resultsWe conducted a longitudinal study in a Chinese cohort of 599 participants. Of these, 266 participants completed a 5.9-year follow-up from June 2014 to December 2021. LTL was assessed at baseline using real-time polymerase chain reaction. Hyperuricemia was defined as serum uric acid ≥420 mmol/L according to Chinese guidelines for diagnosis and treatment of hyperuricemia and gout. Participants who had developed hyperuricemia during follow-up (n = 17) had shorter LTL at baseline. Baseline LTL was independently associated with the development of hyperuricemia at follow-up after adjusting for conventional hyperuricemia risk factors (odds ratio [OR] 2.347 [95% confidence interval [CI] 1.123, 4.906]; P = 0.023). After grouping according to LTL tertiles, the incidence of hyperuricemia was 18.334-fold higher for the first than for the third tertile (OR 18.334 [95%CI 1.786, 191.272]; P = 0.014, P for trend = 0.050). ConclusionOur findings in a prospective cohort suggest that LTL could predict hyperuricemia risk, which might inform the timely prevention and treatment of hyperuricemia.

Quercetin-enriched Lactobacillus aviarius alleviates hyperuricemia by hydrolase-mediated degradation of purine nucleosides

The development of hyperuricemia (HUA) and gout is associated with dysbiosis of the gut microbiota. Quercetin can reduce serum uric acid levels and thus alleviate HUA by modulating the gut microbiota. However, the detailed mechanisms involved in this process are not fully understood. Here, we showed that quercetin significantly reduced the serum uric acid level in a chicken HUA model by altering the chicken cecal microbiota structure and function and increasing the abundance of Lactobacillus aviarius. An L. aviarius strain, CML180, was isolated from the quercetin-treated chicken gut microbiota. Strain characterization indicated that quercetin promoted the growth of L. aviarius CML180 and increased its adhesion, hydrophobicity, and co-aggregation abilities. Gavage of live L. aviarius CML180 to a mouse model of HUA—established by adenosine and potassium oxonate—reduced the serum uric acid level and alleviated HUA. The ability of L. aviarius CML180 to decrease the level of uric acid was due to its degradation of purine nucleosides, which are the precursors for uric acid production. A nucleoside hydrolase gene, nhy69, was identified from the genome of L. aviarius CML180, and the resulting protein, Nhy69, exhibited strong purine nucleoside-hydrolyzing activity at mesophilic temperature and neutral pH conditions. These findings provide mechanistic insights into the potential of quercetin to treat HUA or gout diseases via a specific gut microbe.

Influence of intestinal microecology in the development of gout or hyperuricemia and the potential therapeutic targets.

Gout and hyperuricemia are common metabolic diseases. Patients with purine metabolism disorder and/or decreased uric acid excretion showed increased uric acid levels in the blood. The increase of uric acid in the blood leads to the deposition of urate crystals in tissues, joints, and kidneys, and causes gout. Recent studies have revealed that imbalance of the intestinal microecology is closely related to the occurrence and development of hyperuricemia and gout. Disorder of the intestinal flora often occurs in patients with gout, and high purine and high fructose may induce the disorder of intestinal flora. Short-chain fatty acids and endotoxins produced by intestinal bacteria are closely related to the inflammatory response of gout. This article summarizes the characteristics of intestinal microecology in patients or animal models with hyperuricemia or gout, and explores the relationship between intestinal microecology and gout or hyperuricemia from the aspect of the intestinal barrier, intestinal microorganisms, intestinal metabolites, and intestinal immune system. We also review the current status of hyperuricemia treatment by targeting intestinal microecology.

The Association of Surrogates of Insulin Resistance with Hyperuricemia among Middle-Aged and Older Individuals: A Population-Based Nationwide Cohort Study.

The triglyceride-glucose (TyG) index, triglyceride-to-high-density-lipoprotein-cholesterol (TG/HDL-C) ratio, metabolic score for insulin resistance (METS-IR) and TyG with body mass index (TyG-BMI) have been proposed as indicators of insulin resistance (IR). This study aimed to explore the association between these IR surrogates and their longitudinal variation with the development of hyperuricemia in a middle-aged and older Chinese population. Data from the China Health and Retirement Longitudinal Study (CHARLS) was used to identify 5269 participants aged ≥45 years. Logistic regression was used to assess the effect of IR surrogates and their variations on the risk of hyperuricemia. After four years of follow-up, 517 (9.81%) participants developed incident hyperuricemia. Increased baseline values of TyG, TG/HDL, METS-IR, and TyG-BMI were all significantly associated with higher risks of hyperuricemia. Compared to individuals with maintained low levels of IR surrogates, those with low-to-high and maintained high variation patterns had a significantly higher risk of hyperuricemia. These four IR surrogates have comparable predictive ability for hyperuricemia. This study provides evidence of the associations between IR and hyperuricemia. Early intervention among middle-aged and elderly Chinese individuals with high IR levels may effectively reduce the burden of hyperuricemia.

Lactobacillus gasseri LG08 and Leuconostoc mesenteroides LM58 exert preventive effect on the development of hyperuricemia by repairing antioxidant system and intestinal flora balance.

Currently, hyperuricemia has shown a surprisingly rising trend, which attracts widespread attention due to potentially major health risks. Considering the inevitable side effects of long-term medicine, probiotics are emerging as potential therapeutics due to their ability to improve uric acid metabolism and superior safety. In our study, two strains of probiotics, Lactobacillus gasseri LG08 (LG08) and Leuconostoc mesenteroides LM58 (LM58) isolated from kimchi were evaluated for the prebiotic properties in vitro and uric-lowering effects in vivo. Here, hyperuricemia animal model and 16S rRNA gene amplicons analysis were further studied to investigate whether these probiotics exert different effects in prevention and treatment. In vivo indicators and intestinal flora immunity revealed that both LG08 and LM58 significantly prevent the development and progression of hyperuricemia, repair the antioxidant system and maintain intestinal flora balance in healthy rats, especially LM58. After hyperuricemia was formed, although the effect of LG08 and LM58 could decrease the level of uric acid, the effect to reverse and repair antioxidant levels in the body was limited. In our study, these findings have important implications for hyperuricemia prevention and therapy, and provided more mechanistic insights into the effect of probiotics in hyperuricemia.

FACTOR ASSOCIATED WITH HYPERURICEMIA DEVELOPMENT DURING A 25 YEARS FOLLOW-UP: THE PAMELA STUDY

Objective: HyperUricemia (HU) has been associated with future fatal and non fatal CV events as well as with hypertension and metabolic syndrome development. However, only few data exist regarding the change in Uric Acid (UA) and the development of HU during a population follow-up. In particular, no study analyzed the variations during a very long follow-up. The present study was aimed at evaluating the factors associated with UA changes and HU development during a 25-years follow-up in the PAMELA study. Both the classic cut-off for hyperuricemia and the newly one identified by the Uric Acid Right for Heart Health (URRAH) study were used to define HU. Design and method: We analyzed data collected in 561 subjects of the Pressioni Arteriose Monitorate E loro Associazioni (PAMELA) study with available SUA who complete the 3rd wave study (mean follow-up time 25.2 ± 0.5 years). The classic cut-off of 6/7 mg/dL (females and males respectively) and URRAH one (5.1/5.6 mg/dL for females and males) were used for HU definitions. Results: Mean UA value during follow-up increase from 4.7 ± 1.1 to 5.0 ± 1.2 mg/dL (p &lt; 0.001) with a mean increase of 0.3 ± 1.1 mg/dL. UA changes significanlty correlated with baseline UA (r = -0.39, p &lt; 0.001) and creatinine (r = -0 - 21, p &lt; 0.001). With the classic cut-off (6/7 mg/dL) 9.1% of the subjects develop HU and this was associated at the multivariate model with age, sex (male), baseline diastolic Blood Pressure (BP) (OR 1.038, p = 0.02) and UA (OR 2.62, p &lt; 0.001). With the new URRAH cut-off 19.1% of the subjects develop HU. At the multivariate model variables associated were gender (male) and baseline 24h systolic BP (OR 1.05, p &lt; 0.001), tryglicerides (OR 1.01, p = 0.01) and UA (4.99, p &lt; 0.001). Conclusions: The present study provide evidence that in the PAMELA study during the 25 year follow-up there is a progressive increase in UA. Baseline UA is the most important factor associated with HU development. However, also age, gender, triglycerides and BP could help to identify subjects that most probably will develop HU.

Triglyceride-Glucose Index is Significantly Associated with the Risk of Hyperuricemia in Patients with Nonalcoholic Fatty Liver Disease.

The triglyceride-glucose (TyG) index is a new index of insulin resistance (IR), and its association with hyperuricemia (HUA) is unclear. The aim of this study was to investigate whether TyG is an independent risk factor for hyperuricemia (HUA) in patients with nonalcoholic fatty liver disease (NAFLD). We retrospectively analyzed 461 patients with ultrasound-confirmed NAFLD and calculated the TyG index. Multivariate logistic regression was used to analyze the relationship between the TyG index and HUA in NAFLD patients. The correlation between the TyG index and HUA was further confirmed by a restricted cubic spline. Furthermore, the stability of the association between TyG index and HUA was examined using subgroup analysis. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive value of the TyG index on HUA. Multivariate linear regression was used to analyze the linear relationship between the TyG index and serum uric acid. A total of 166 HUA patients and 295 non-HUA patients were included in the study. The results of multivariate logistic regression analysis showed that after controlling the confounding risk factors, TyG was still an independent risk factor for HUA (OR = 2.00, 95% CI: 1.38 -2.91, p < 0.001). Restricted cubic splines showed that HUA risk increased linearly with TyG across the entire TyG range. The ROC curve showed that TyG index was better than triglyceride in predicting HUA in NAFLD patients, with AUC values of 0.62 and 0.59, respectively. Multiple linear regression analysis showed that TyG index was significantly positively correlated with blood uric acid (B = 1.37, 95% CI: 0.67-2.08, p < 0.001). TyG index is an independent risk factor for HUA in patients with NAFLD. The increase of the TyG index level is closely related to the occurrence and development of HUA in patients with NAFLD.

Disorder of purine metabolism in the etiopathogenesis of urate nephrolithiasis

Urinary stone disease (USD) is a polyetiological urological disease caused by both exogenous and endogenous factors, including hereditary ones. It is characterized by the appearance of stones in the kidneys and urinary tract, and a tendency to relapse, often with a severe course. Almost 25 % of stones consist of uric acid (UA). The leading role in the pathogenesis of urate nephrolithiasis (UN) is played by disorders of purine metabolism, which are characterized by the development of hyperuricemia (HU) and hyperuricuria. The aim of the work is to review modern literary sources on the role of purine metabolism disorders in the etiopathogenesis of UN. Results. The development of UN depends on the constancy of the acidic urine pH, as well as on a decrease in diuresis, HU and hyperuricuria. UA is the final metabolite of purine metabolism and the main stone-forming substance in patients with UN. HU develops both due to uncompensated disorders of purine metabolism with a decrease in renal secretion and intestinal uricolysis (excretion pathway) and excessive intake of purine bases in the body and their increased synthesis in vivo (metabolic pathway). Citric acid, as one of the main metabolites of the tricarboxylic acid (TCA) cycle, is connected through the corresponding substrates to the formation of purines and the metabolite of amino acid metabolism, glutamine. TCA is connected to the cycles of urea, glyoxylate and purine bases through α-ketaglutaric acid. It is a substrate of citric acid, and it affects the synthesis of glutamate, which combines with ammonia to form glutamine, used in the cycle of purine synthesis. Conclusions. The role and diagnostic value of purine metabolism upsets, disorders of the TCA (citric acid), amino acid metabolism (glutamine), the activity of xanthine oxidase is a key enzyme in purine synthesis which passes through TCA with the participation of its metabolite α-ketaglutarate, have been established. TCA is bound to glutamine, rich in nitrogen, which is necessary for the synthesis of purine bases.

Uric acid en route to gout.

Gout and hyperuricemia (HU) have generated immense attention due to increased prevalence. Gout is a multifactorial metabolic and inflammatory disease that occurs when increased uric acid (UA) induce HU resulting in monosodium urate (MSU) crystal deposition in joints. However, gout pathogenesis does not always involve these events and HU does not always cause a gout flare. Treatment with UA-lowering therapeutics may not prevent or reduce the incidence of gout flare or gout-associated comorbidities. UA exhibits both pro- and anti-inflammation functions in gout pathogenesis. HU and gout share mechanistic and metabolic connections at a systematic level, as shown by studies on associated comorbidities. Recent studies on the interplay between UA, HU, MSU and gout as well as the development of HU and gout in association with metabolic syndromes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular, renal and cerebrovascular diseases are discussed. This review examines current and potential therapeutic regimens and illuminates the journey from disrupted UA to gout.

Comparison of different insulin resistance surrogates to predict hyperuricemia among U.S. non-diabetic adults.

Although it has been well-acknowledged that insulin resistance (IR) plays a critical role in the development of hyperuricemia (HU), specific relationship between IR and HU in non-diabetic patients remains rarely studied, and there is still no large-scale research regarding this issue. This study aims to explore the association between triglyceride glucose (TyG), TyG with body mass index (TyG-BMI), the ratio of triglycerides divided by high-density lipoprotein cholesterol (TG/HDL-C), metabolic score for insulin resistance (METS-IR), and the risk of HU in non-diabetic patients in The United States of America. Data from the National Health and Nutrition Examination Survey (NHANES) enrolling a representative population aged ≥18-year-old were included to calculate these four indexes. Logistic regression analysis was applied to describe their associations and calculate odds ratios (OR) while the Receiver Operating Characteristic curve was utilized to assess the prediction ability of these four indexes. A total of 7,743 people (3,806 males and 3,937 females, mean age: 45.17 ± 17.10 years old) were included in this study, among whom 32.18% suffered from HU. After adjustment for sex, age, ethnicity, education background, smoking status, drinking status, systolic blood pressure (SBP), diastolic blood pressure (DBP), metabolic equivalent values (METs), total cholesterol, low-density lipoprotein cholesterol, and estimated glomerular filtration rate, it showed that all four indexes were closely related to HU. Compared with the lowest quartile, OR of the highest quartile of these four indicators for HU were as following respectively: TyG: 5.61 (95% CI: 4.29-7.32); TyG-BMI: 7.15 (95% CI: 5.56-9.20); TG/HDL-C: 4.42 (95% CI: 3.49-5.60); METS-IR: 7.84 (95% CI: 6.07-10.13). TyG, TyG-BMI, TG/HDL-C and METS-IR had moderate discrimination ability for HU, with an AUC value of 0.66 (95% CI: 0.65-0.68), 0.67 (95% CI: 0.65-0.68), 0.68 (95% CI: 0.67-0.69) and 0.68 (95% CI: 0.66-0.69) respectively. Each index showed better prediction ability for HU risk in females than in males. It was found that the risk of HU was positively associated with the elevation of TyG, TyG-BMI, TG/HDL-C and METS-IR in a large-scale population of U.S., and TyG-BMI and METS-IR have a better ability to identify HU in both genders.