Gout, the most common inflammatory arthritis, affects as many as 5.1% of the adult population. Classically, gout is conceived as four sequential phenotypic states: 1) asymptomatic hyperuricemia 2) acute gout flare 3) inter-critical gout (gout between flares); and 4) tophaceous gout. However, these four states are paralleled by a fifth state, consisting of vascular involvement. The mechanisms and consequences of vascular gout are incompletely elucidated. In vitro and animal models indicate that soluble urate adversely affects vascular endothelium and smooth muscle. The recent discovery that soluble urate can be transported intracellularly to alter cell metabolism and epigenetics (trained innate immunity) suggests additional impacts of urate on leukocytes and endothelium. Once gout has progressed to flares, the vasculature is exposed to inflammatory mediators, both during flares and to a lesser but persistent extent inter-critically, suggesting additional mechanisms of gout's effect. We have reported that patients with gout have diminished endothelial function measured by brachial artery flow-mediated dilation. ACR gout guideline-concordant treatment improves endothelial function but is less effective in patients with cardiometabolic comorbidities. Moreover, treatment of gout patients with the anti-inflammatory colchicine and urate lowering therapy improves endothelial function and reduces the risk of both incident coronary artery disease (CAD), and MACE in patients with established CAD.

To assess the association between Body Roundness Index (BRI) and chronic kidney disease (CKD) risk in individuals with diabetes.

A cross-sectional analysis of 6,971 individuals with diabetes from NHANES 1999-2018 was conducted. BRI was calculated using waist circumference and height. CKD was defined as eGFR < 60 mL/min/1.73 m2 or ACR ≥ 30 mg/g. Weighted multivariable logistic regression assessed the BRI-CKD association. Subgroup and mediation analyses assessed heterogeneity and potential pathways.

Higher BRI was independently associated with increased CKD risk. In fully adjusted models, each unit increase in BRI corresponded to 10.5 % higher odds of CKD (OR: 1.109; 95 % CI: 1.040-1.183; p = 0.002). Stronger associations were found in males, younger individuals, and those with elevated blood pressure or uric acid. An inverse association was observed in participants with severe proteinuria. Mediation analysis showed partial effects through HbA1c (3.9 %), serum creatinine (27.7 %), and albumin (-26.2 %).

BRI is an independent marker of CKD risk in individuals with diabetes and may reflect contributions from glycaemic control, kidney function, and nutritional status. It may serve as a practical tool for CKD risk stratification.

Hyperuricemia is a metabolic disorder primarily associated with gout and implicated in various metabolic inflammatory diseases. While the role of monosodium urate crystals triggering inflammation has been well-documented, recent findings suggest that soluble high uric acid (HUA) also induces pro-inflammatory cytokine production in human monocytes. However, the comprehensive effects of HUA levels on macrophage dysfunction and the underlying mechanisms remain underexplored. This study employs urate oxidase knockout (UOX-KO) and receptor for advanced glycation end products deficiency (RAGE-/-) mouse models to elucidate macrophage function and its mechanistic pathways. Our results demonstrate that HUA promotes M1 polarization and migration of macrophages while impairing their phagocytic ability. This process is mediated through the high mobility group box 1 (HMGB1)-RAGE- ROS axis. Notably, RAGE deficiency in bone marrow-derived cells partially mediates these effects. Pathologically, elevated HMGB1 and monocyte chemoattractant protein 1 levels in pancreatic islets increases macrophage infiltration in UOX-KO mice. Treatment with the FPS-ZM1, as a pharmacological RAGE inhibitor, effectively decreases serum UA levels, ameliorates islet inflammation and insulin resistance. These findings suggest that soluble HUA serves as a pro-inflammatory trigger through the HMGB1-RAGE-ROS axis, and that RAGE inhibition may mitigate these effects by decreasing inflammatory macrophage infiltration in the islets. Additionally, the influence of UA on macrophages extends beyond gout, potentially contributing to the pathogenesis of other metabolic inflammatory conditions, such as atherosclerosis, non-alcoholic steatohepatitis, obesity, and hyperlipidemia.

There is an increasing interest in the role of fructose as a major driver of non-alcoholic fatty liver disease (NAFLD), and it is linked closely with the intake of sugar. However, there has also been the recognition that fructose can be produced directly from intracellular glucose via the evolutionarily conserved polyol pathway whose access is governed by aldose reductase (AR). The purpose of this article is to review the biochemistry of AR and the role of the polyol pathway in opening fructose metabolism. This article provides a new perspective about AR and the other key enzymes surrounding the decision to divert glucose into the polyol pathway which suggests that the production of endogenous fructose may be of much greater significance than historically viewed. There are important aspects of the regulation of the polyol pathway and its committal step catalyzed by AR, which supports the notion that fructose-uric acid pathway is activated by elevated glucose with the downstream consequence of NAFLD and perhaps other chronic metabolic diseases.

The search for biological markers that can be reliably linked to aggression and antisocial behavior has been central to the work of biological criminology. One such marker, uric acid, has long been suspected to play a causative role in promoting anger, irritability, aggression, and violence. Here, in this perspective article, we revisit some of the historical interest in uric acid as a compound relevant to brain and behavior, and reflect these early accounts off emergent scientific research. Advances in brain sciences, including neuropsychiatry and neuromicrobiology, have allowed for a more sophisticated understanding of potential mechanistic pathways linking uric acid with cognition and behavior. The updated science suggests that some of the early ideas surrounding uric acid and criminology had credibility. The available research strongly suggests that uric acid, as a potential biomarker of risk, is worthy of further research and close scrutiny. Informed by emergent gut-brain-microbiome research, we argue that certain aspects of early-to-mid-20th-century biological criminology were prematurely abandoned. From a legalome perspective, further advances surrounding uric acid and other gut-brain biomarkers can aid in shaping more humane, scientifically grounded policies that recognize the interplay between biology and environment.

Based on the hypothesis that hyperuricemia is a modifiable risk factor for chronic kidney disease (CKD) progression, there is an expectation that urate-lowering therapy (ULT) could delay the progression of CKD. Here, we investigated changes in kidney function and the association of the serum uric acid (sUA) level and kidney function during ULT in patients with gout. To do this we conducted post-hoc analysis on patients who received ULT with either febuxostat or allopurinol for more than six months in the CARES trial. The estimated glomerular filtration rate (eGFR) slope (annual rate of change in eGFR) was calculated using the CKD-EPI creatinine equation and linear mixed modeling. Among the 5,002 patients with gout, 3,264 (65.3%) demonstrated an increased eGFR while receiving ULT over a median follow-up of 2.5 years. Increased average sUA levels were significantly associated with declines in eGFR slope (per 1 mg/dL increase, (adjusted beta of -0.1912). Propensity score matched analysis demonstrated a significant association between low average sUA levels below 6 mg/dL during ULT and a reduced risk of eGFR decline (adjusted odds ratio: 0.66, 95% confidence interval 0.57-0.77). Despite the well-documented natural decline of eGFR over time in the general population, more than half of the patients enrolled in the CARES trial did not experience declines in eGFR while receiving ULT. Thus, our study shows maintaining low sUA levels with ULT was significantly associated with a decreased risk of CKD progression in patients with gout.

Uric acid is a major contributor to the total antioxidant capacity of human plasma. However, this endogenous substance's antioxidant and prooxidant properties have not yet been reported.

In this study, the comet assay was employed in vitro to determine the effect of uric acid on DNA damage in human lymphocytes and leukocytic DNA damage in hyperuricemia patients with and without renal failure.

DNA damage in lymphocytes occurred at uric acid concentrations of ≥600 μM. Adding catalase to the uric acid solution diminished the damaging effect, indicating that hydrogen peroxide mediated the prooxidant activity. Moreover, adding Fe2+ did not enhance the DNA damage, suggesting that the urate's prooxidant activity is independent of the Fenton reaction. The unstable nature of uric acid at nearly neutral and acidic pH levels resulted in autooxidation and the generation of hydrogen peroxide. Maintaining the stability of uric acid in vivo may lead to the consumption of antioxidants in the body and affect the antioxidant status. Hyperuricemia patients with and without renal failure had higher levels of leukocytic DNA damage compared to healthy individuals. However, there was no significant difference in leukocytic DNA damage between hyperuricemia patients with and without renal failure, which showed that the damaging effect was not due to renal failure. A correlation study suggested that serum uric acid level had a stronger correlation with DNA damage than the severity of renal failure as indicated by serum creatinine or urea.

Uric acid demonstrated prooxidant activity in both in vitro and in vivo studies, which was mediated by the production of hydrogen peroxide and independent of both the Fenton reaction and renal failure.

Chronic kidney disease (CKD) is a prevalent global health concern, significantly linked to increased cardiovascular morbidity and mortality. Among various risk factors, uric acid (UA) has emerged as a potentially modifiable contributor to cardiovascular complications in CKD patients.

Elevated serum uric acid levels frequently occur in individuals with CKD and are associated with the development of atherosclerosis (AS). Uric acid has been demonstrated to exacerbate inflammatory processes, promote oxidative stress, and cause endothelial dysfunction, which are critical factors that drive the formation of atherosclerotic plaques. Furthermore, high uric acid levels can worsen renal function, establishing a detrimental cycle that amplifies cardiovascular risk.

This review investigates the complex interconnection between UA and AS in patients with CKD, highlighting the underlying mechanisms and therapeutic considerations. A more profound comprehension of this relationship is essential for enhancing cardiovascular health and outcomes in this vulnerable population.

Recent individual studies have indicated that ultra-processed food (UPF) consumption may be associated with the incidence of chronic kidney disease (CKD). We conducted a systematic review and meta-analysis based on those longitudinal studies evaluating the relationship between UPF consumption and the risk of incident CKD, and synthesizing the results.

PubMed, Embase, The Cochrane Library, Web of Science, and Scopus were searched from inception through 22 March 2023. Any longitudinal studies evaluating the relationship between UPF consumption and the risk of incident CKD were included. Two researchers independently conducted the literature screening and data extraction. RR and its 95% CI were regarded as the effect size. The Newcastle-Ottawa Scale (NOS) was applied to assess the quality of the studies included, and the effect of UPF consumption on the risk of incident CKD was analyzed with STATA version 15.1. This study's protocol was registered in PROSPERO (CRD42023411951).

Four cohort studies with a total of 219,132 participants were included after screening. The results of the meta-analysis suggested that the highest UPF intake was associated with an increased risk of incident CKD (RR = 1.25; 95% CI: 1.18-1.33).

High-dose UPF intake was associated with an increased risk of incident CKD. However, the underlying mechanisms remain unknown. Thus, more standardized clinical studies and further exploration of the mechanisms are needed in the future.

To explore the relationship between the serum uric acid to creatinine (UA/Cr) ratio and the prevalence of hypertension.

In this cross-sectional study, we included 8571 individuals from the China Health and Nutrition Survey. Logistic regression analysis and restricted cubic spline (RCS) were used to analyze the relationship between the UA/Cr ratio and hypertension.

Compared with individuals without hypertension, individuals with hypertension had higher UA/Cr ratios. Multivariate logistic regression analysis showed that a higher UA/Cr ratio was closely related to a higher risk of hypertension (as a continuous variable, OR: 1.054, 95% CI: 1.014-1.095, p = 0.007; as a categorical variable, Q3 vs. Q1, OR: 1.183, 95% CI: 1.011-1.384, p = 0.035; Q4 vs. Q1, OR: 1.347, 95% CI: 1.146-1.582, p < 0.001). Subgroup analysis revealed that the correlation between the UA/Cr ratio and hypertension risk was stable in all subgroups except for the subgroup with diabetes and the subgroup with a BMI ≥ 28 kg/m2 (p < 0.05). Sensitivity analysis confirmed the robustness of the relationship between a higher UA/Cr ratio and a higher risk of hypertension (p < 0.05). The RCS showed that the UA/Cr ratio was nonlinearly related to hypertension risk. Further threshold effect showed that only a UA/Cr ratio less than 5.0 was related to hypertension risk (OR: 1.178, 95% CI: 1.086-1.278, p < 0.001), and the 2-piecewise linear regression model was superior to the 1-line linear regression model (p < 0.05).

The UA/Cr ratio was associated with the prevalence of hypertension.

High-fructose corn syrup (HFCS) has been a subject of intense debate due to its association with cardiovascular risks. This study investigates the potential protective effects of selenium (Se) supplementation against cardiac damage induced by HFCS. Thirty-two male Wistar albino rats were divided into four equal groups: control, CS (20%-HFCS), CS with Se (20%-HFCS, 0.3 mg/kg-Se), and Se (0.3 mg/kg-Se) only. After a 6-week period, heart and aorta tissues were collected for histopathological, immunohistochemical, biochemical, and genetic analyses. HFCS consumption led to severe cardiac pathologies, increased oxidative stress, and altered gene expressions associated with inflammation, apoptosis, and antioxidant defenses. In the CS group, pronounced oxidative stress within the cardiac tissue was concomitant with elevated Bcl-2-associated X protein (Bax) expression and diminished expressions of B-cell-lymphoma-2 (Bcl-2), nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), and silenced information regulator 1 (SIRT1). Se supplementation mitigated these effects, showing protective properties. Immunohistochemical analysis supported these findings, demonstrating decreased expressions of caspase-3, tumor necrosis factor-alpha (TNF-α), IL-1β, and vascular endothelial growth factor (VEGF) in the CS + Se group compared to the CS group. The study suggests that Se supplementation exerts anti-inflammatory, antioxidant, and antiapoptotic effects, potentially attenuating HFCS-induced cardiovascular toxicity. These findings highlight the importance of dietary considerations and selenium supplementation in mitigating cardiovascular risks associated with HFCS consumption.

Risk factor modification may decrease the risk of cardiovascular disease (CVD). Whether risk factor modification can mitigate the effect of hyperuricemia on CVD is unclear. This study aimed to investigate the risk of CVD among individuals with hyperuricemia, according to risk factors on target, compared with controls without hyperuricemia.

This prospective study included 91,722 participants free of CVD at baseline (2006-2007) of the Kailuan study. Individuals with hyperuricemia were categorized according to the number of seven selected risk factors within the guideline-recommended target range (nonsmoking, physical activity, healthy diet, guideline-recommended levels of body mass index, blood pressure, fasting blood glucose, and total cholesterol). During a median follow-up of 13.00 years, 671 out of 6740 individuals (9.96%) with hyperuricemia and 6301 out of 84,982 control subjects (7.41%) had incident CVD. Compared with control subjects without hyperuricemia, individuals with hyperuricemia who had 4 or 5 to 7 risk factors on target had no significant excess CVD risk, the hazard ratio (HR) (95% confidence internal [CI]) was 0.93 (0.79-1.10) and 0.88 (0.71-1.10), respectively. Among individuals with hyperuricemia, excess CVD risk decreased stepwise for a higher number of risk factors on target, the HR of CVD associated with per additional risk factor within target range was 0.82 (95% CI, 0.77-0.87). Similar results were yielded for CVD subtypes.

Among individuals with hyperuricemia, excess CVD risk decreased stepwise for a higher number of risk factors within target.

Kidney disease is a common complication of multiple myeloma (MM) and a risk factor for increased morbimortality. In this retrospective cohort study based on medical records, we analyzed the kidney function of patients with renal disease related to MM during the first year of treatment. All patients included were consecutively admitted to the outpatient services of two hospitals between January 2009 and January 2019 and met the diagnostic criteria for MM regardless of the reason for seeking medical help. We excluded patients who had kidney disease or who were on dialysis before MM diagnosis. We investigated the factors associated with renal function recovery using multivariate analysis. We evaluated 167 patients (median age of 66 ± 11.49 years). Almost half of the patients had arterial hypertension (76; 45.5%). The majority had International Staging System (ISS) grades 3 (73; 43.7%) or 2 (60; 35.9%). Seventy-four (44%) patients had an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² at the time of MM diagnosis. Fifty-two patients (31%) underwent hematopoietic stem cell transplantation (HSCT). After 12 months, 4 (2.3%) patients needed dialysis, and 18 (10.7%) died. The factors associated with an eGFR < 60 ml/min/1.73 m² were anemia, hyperuricemia, 24-hour proteinuria > 1.0 g, and extramedullary plasmacytoma. However, only baseline renal function (eGFR > 60 ml/min/1.73 m2) and HSCT were associated with greater recovery of renal function at 12 months of follow-up.

It is well-known that serum uric acid (SUA) can increase the risk of hypertension, diabetes, obesity and dyslipidemia. However, its independent association with the risk of cardiovascular diseases (CVD) is controversial particularly in different populations. Hence, this study was aimed to assess an independent association of SUA with CVD risk in a Punjabi Pakistani cohort.

This is a retrospective observational study in which 502 human subjects having CVD, hypertension and/or diabetes were grouped based on SUA levels as normouricemia (n = 266) and hyperuricemia (n = 236). Role of SUA was assessed in increasing the risk of CVD independent of other key confounding factors (i.e. age, gender, dyslipidemia, hypertension, diabetes, dietary and life-style habits). All clinical and biochemical data were analyzed in SPSS (ver. 20).

Subjects aged 55 ± 13 years were of both genders (males: 52%). SUA levels were significantly different among clinical subtypes of CVD [i.e. acute coronary syndrome (ACS), myocardial infarction (MI) and heart failure (HF)]. Spearman correlation showed a significantly positive association between CVD and SUA (rho = 0.149, p < 0.001). Multivariate logistic regression of SUA quartiles showed that hyperuricemia is associated with CVD [3rd quartile: OR: 1.78 (CI: 1.28-2.48), p = 0.001 and 4th quartile: OR: 2.37 (CI: 1.72-3.27), p < 0.001]. Moreover, this association remained significant even after adjusting for confounding factors.

This study showed that SUA is positively associated with CVD, thus it can act as an independent risk factor for CVD.

Uric acid (UA), the terminal breakdown product of purine metabolism, possesses contradictory roles, functioning both as an inflammatory mediator and as an antioxidant. Its clinical relevance, particularly in geriatric populations, remains a topic of ongoing debate. Aiming to elucidate whether circulating UA is detrimental or beneficial to human health, we investigate the association between serum UA concentrations and the frailty index-a comprehensive measure of biological aging in a nationally representative cohort of community-dwelling older adults.

We conducted a population-based, cross-sectional study utilizing data from the Korea National Health and Nutrition Examination Survey. The sample included 4268 participants aged 65 years and above. A deficit accumulation frailty index (FI) was constructed using 38 items that assess physical, cognitive, psychological, and social domains. Based on the FI, participants were categorized into non-frail (FI ≤ 0.15), pre-frail (0.15 < FI ≤ 0.25), or frail (FI > 0.25). Serum UA levels were quantified through a colorimetric enzymatic assay.

After controlling for confounders such as age, sex, socioeconomic status (including income and education level), lifestyle factors (smoking status), and medical history (hypertension, diabetes, dyslipidemia, stroke, cardiovascular diseases), and body mass index, serum UA levels were observed to be significantly higher in frail participants compared with their non-frail counterparts (P < 0.001). Furthermore, serum UA concentrations demonstrated a positive correlation with the FI (P < 0.001), and the odds ratio for frailty per 1 mg/dL increase in serum UA was 1.22 (P < 0.001). Additionally, older adults in the highest quartile of UA levels exhibited a significantly higher FI and 1.66-fold increased odds of frailty compared with those in the lowest quartile (P = 0.011 and P = 0.005, respectively).

These findings suggest that elevated circulating UA levels may act as a pro-aging factor rather than an anti-aging one in older adults, highlighting its potential role in accelerating biological aging. The data further support the utility of serum UA as a potential blood-based biomarker for frailty in this demographic, contributing to the expanding evidence on its significance in geriatric health assessments.

Hyperuricemia, characterized by elevated levels of serum uric acid (SUA), is linked to a spectrum of commodities such as gout, cardiovascular diseases, renal disorders, metabolic syndrome, and diabetes, etc. Significantly impairing the quality of life for those affected, the prevalence of hyperuricemia is an upward trend globally, especially in most developed countries. UA possesses a multifaceted role, such as antioxidant, pro-oxidative, pro-inflammatory, nitric oxide modulating, anti-aging, and immune effects, which are significant in both physiological and pathological contexts. The equilibrium of circulating urate levels hinges on the interplay between production and excretion, a delicate balance orchestrated by urate transporter functions across various epithelial tissues and cell types. While existing research has identified hyperuricemia involvement in numerous biological processes and signaling pathways, the precise mechanisms connecting elevated UA levels to disease etiology remain to be fully elucidated. In addition, the influence of genetic susceptibilities and environmental determinants on hyperuricemia calls for a detailed and nuanced examination. This review compiles data from global epidemiological studies and clinical practices, exploring the physiological processes and the genetic foundations of urate transporters in depth. Furthermore, we uncover the complex mechanisms by which the UA induced inflammation influences metabolic processes in individuals with hyperuricemia and the association with its relative disease, offering a foundation for innovative therapeutic approaches and advanced pharmacological strategies.

Phellinus igniarius is an important medicinal and edible fungus with diverse biological activities. This study aimed to investigate the effects of aqueous extract from P. igniarius (API) on the treatment of hyperuricemia (HUA) and related kidney damage. The chemical constituents of API were determined. The therapeutic effects of API on HUA and renal injury were assessed in adenine/potassium oxonate (PO)-treated mice. The constituent analysis of API revealed a predominance of polysaccharides (33.4 %), followed by total flavonoids (9.1 %), and total triterpenoids (3.5 %). Compared to control, the adenine/PO treatment greatly elevated serum uric acid (UA) levels but this elevation was attenuated by API. In the liver, the expression and activity of xanthine oxidase (XOD) were increased by HUA which were diminished by API. Furthermore, API was found to enhance the expression of UA transporter ABCG2 in the kidney and intestine of HUA mice, suggesting elevating UA excretion. Additionally, API ameliorated HUA-induced renal injury, as indicated by reduced serum BUN/creatinine levels, decreased glomerular and tubular damage, and lowered fibrotic levels. Network pharmacology analysis predicted that P. igniarius may regulate mitochondrial function to improve HUA-related renal injury. This prediction was then substantialized by the API-induced upregulation of NAD+/NADH ratio, ATP level, SOD2 activity, and expression of SOD2/PCG-1α/PPARγ in the kidney of HUA mice. Our results demonstrate that API may effectively ameliorate HUA by reducing UA production in the liver and enhancing UA excretion in the kidney and intestine, and it might be a potential therapy to HUA-related renal injury.

Hyperuricemia, hyperglycemia, hypertension, hyperlipidemia, and hyperhomocysteinemia are all established risk factors for chronic kidney disease (CKD), and their interplay could exacerbate CKD progression. This study aims to evaluate the potential mediation effects of hyperglycemia, hypertension, hyperlipidemia, and hyperhomocysteinemia on the association between hyperuricemia (HUA) and chronic kidney disease (CKD).

We collected electronic medical record data from 2055 participants who underwent physical examinations at the Affiliated Hospital of Qingdao University. The data were utilized to investigate the mediating effect of various factors including systolic blood pressure (SBP), diastolic blood pressure (DBP), homocysteine (HCY), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), blood glucose (Glu), and hemoglobin A1c (HbA1c) on the relationship between HUA and CKD.

Upon adjusting for confounding variables, mediation analysis indicated that only HCY acted as a mediator in the HUA-CKD relationship (p value < 0.05), exhibiting a statistically significant mediation effect of 7.04%. However, after adjustment for multiple testing, none of these variables were statistically significant.

Considering the observed associations between hyperuricemia, hyperglycemia, hypertension, hyperlipidemia, and CKD, none of the factors of interest remained statistically significant after adjusting for multiple testing as potential mediators of hyperuricemia on CKD.

The current study aimed to assess the relationships between oxidative balance score (OBS) and OBS subclasses (dietary and lifestyle OBS) with risks of hyperuricemia (HUA) and gout among American adults.

Participants in the National Health and Nutrition Examination Survey from 2007 to 2018 were initially recruited and then the final sample was restricted to adults without missing values about serum uric acid, gout, OBS, and covariates. Rao-Scott adjusted chi-square test and analysis of variance were utilized to compare the baseline characteristics in adults of different quartiles of OBS, while the weighted stepped logistic regression models were used to explore the associations of overall, dietary, and lifestyle OBS with the risks of HUA and gout. Weighted restricted cubic spline analyses were conducted to explore the nonlinear dose-response associations.

The final sample consisted of 22,705 participants aged 20 years and older, which was representative of approximately 197.3 million non-institutionalized American adults. HUA and gout prevalence decreased with OBS quartiles. Compared with adults in the first quartile of OBS, those in the second (OR: 0.85, 95% CI: 0.72-0.99), third (OR: 0.71, 95% CI: 0.58-0.85), and fourth (OR: 0.48, 95% CI: 0.38-0.61) quartiles of OBS had reduced risks of hyperuricemia. Similarly, adults in the second (OR: 0.70, 95% CI: 0.51-0.97) quartile of OBS was associated with lower gout risk in comparison to adults in the lowest quartile. Regarding OBS subclasses, dietary and lifestyle OBS were both negatively correlated with the risk of HUA, and only higher lifestyle OBS was significantly associated with lower gout risk. Furthermore, the subgroup analyses and interaction effects also substantiated similar effects. Significant nonlinear dose-response relationships were observed between overall, dietary, and lifestyle OBS with HUA risk as well as that of lifestyle OBS with gout risk.

This study strongly suggests the significant negative associations of OBS with HUA and gout in American adults and provides a dietary and lifestyle guideline to reduce the risks.

Xanthine Oxidoreductase (XOR) is a ubiquitous, essential enzyme responsible for the terminal steps of purine catabolism, ultimately producing uric acid that is eliminated by the kidneys. XOR is also a physiological source of superoxide ion, hydrogen peroxide, and nitric oxide, which can function as second messengers in the activation of various physiological pathways, as well as contribute to the development and the progression of chronic conditions including kidney diseases, which are increasing in prevalence worldwide. XOR activity can promote oxidative distress, endothelial dysfunction, and inflammation through the biological effects of reactive oxygen species; nitric oxide and uric acid are the major products of XOR activity. However, the complex relationship of these reactions in disease settings has long been debated, and the environmental influences and genetics remain largely unknown. In this review, we give an overview of the biochemistry, biology, environmental, and current clinical impact of XOR in the kidney. Finally, we highlight recent genetic studies linking XOR and risk for kidney disease, igniting enthusiasm for future biomarker development and novel therapeutic approaches targeting XOR.

Purpose: This study evaluated the association between maternal serum uric acid-to-creatinine ratio (SUA/SCr) in the first trimester and adverse maternal and neonatal outcomes. Methods: A prospective birth cohort study was conducted between 2018 and 2021. Logistic regression models and restricted cubic splines were utilized to estimate the associations between the SUA/SCr ratio and feto-maternal pregnancy outcomes. Women were stratified according to maternal age and pre-pregnancy body mass index. Results: This study included 33,030 pregnant women with live singleton pregnancies. The overall prevalence of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), cesarean delivery, preterm birth, large-for-gestational age (LGA), small-for-gestational age, and low Apgar scores were 15.18%, 7.96%, 37.62%, 4.93%, 9.39%, 4.79% and 0.28%, respectively. The highest quartile of SUA/SCr was associated with the highest risk of GDM (odds ratio [OR] 2.14, 95% CI 1.93-2.36), PIH (OR 1.79, 95% CI 1.58-2.04), cesarean delivery (OR 1.24, 95% CI 1.16-1.33), and preterm birth (OR 1.30, 95% CI 1.12-1.51). The associations between SUA/SCr with adverse pregnancy outcomes showed linear relationships except for GDM (P < 0.001 for all, P < 0.001 for non-linearity). Subgroup analyses revealed that the associations between the SUA/SCr ratio and the risks of PIH and LGA were significantly stronger in younger pregnant women (P = 0.033 and 0.035, respectively). Conclusion: Maternal SUA/SCr levels were associated positively with the risk of adverse pregnancy outcomes. Timely monitoring of SUA and SCr levels during early pregnancy may help reduce the risk of adverse pregnancy outcomes and provide a basis for interventions.

The prevalence of non-alcoholic fatty liver (NAFLD) has increased recently. Subjects with NAFLD are known to have higher chance for renal function impairment. Many past studies used traditional multiple linear regression (MLR) to identify risk factors for decreased estimated glomerular filtration rate (eGFR). However, medical research is increasingly relying on emerging machine learning (Mach-L) methods. The present study enrolled healthy women to identify factors affecting eGFR in subjects with and without NAFLD (NAFLD+, NAFLD-) and to rank their importance.

To uses three different Mach-L methods to identify key impact factors for eGFR in healthy women with and without NAFLD.

A total of 65535 healthy female study participants were enrolled from the Taiwan MJ cohort, accounting for 32 independent variables including demographic, biochemistry and lifestyle parameters (independent variables), while eGFR was used as the dependent variable. Aside from MLR, three Mach-L methods were applied, including stochastic gradient boosting, eXtreme gradient boosting and elastic net. Errors of estimation were used to define method accuracy, where smaller degree of error indicated better model performance.

Income, albumin, eGFR, High density lipoprotein-Cholesterol, phosphorus, forced expiratory volume in one second (FEV1), and sleep time were all lower in the NAFLD+ group, while other factors were all significantly higher except for smoking area. Mach-L had lower estimation errors, thus outperforming MLR. In Model 1, age, uric acid (UA), FEV1, plasma calcium level (Ca), plasma albumin level (Alb) and T-bilirubin were the most important factors in the NAFLD+ group, as opposed to age, UA, FEV1, Alb, lactic dehydrogenase (LDH) and Ca for the NAFLD- group. Given the importance percentage was much higher than the 2nd important factor, we built Model 2 by removing age.

The eGFR were lower in the NAFLD+ group compared to the NAFLD- group, with age being was the most important impact factor in both groups of healthy Chinese women, followed by LDH, UA, FEV1 and Alb. However, for the NAFLD- group, TSH and SBP were the 5th and 6th most important factors, as opposed to Ca and BF in the NAFLD+ group.

Improved oocyte competence for embryo development and pregnancy was observed following ovulation of preovulatory follicles with greater physiological maturity, as indicated by estradiol production, prior to the gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) surge. It was hypothesized that follicular fluid from preovulatory follicles of greater maturity better supports the maturing oocyte's metabolic requirements and improves embryo development. The objective was to determine if differences in preovulatory follicular fluid due to follicle maturity influence oocyte metabolism during in vitro maturation (IVM) and affect embryo development. Bovine preovulatory follicular fluid was collected 18 h after a GnRH-induced LH surge. Serum estradiol concentration at GnRH administration categorized follicles as greater or lesser maturity. Immature bovine oocytes were submitted to 24 h IVM in medium supplemented with 20% follicular fluid from preovulatory follicles of greater or lesser maturity. Embryo development was recorded. Oocyte maturation media and media conditioned by developing embryos were submitted for metabolomics. A randomized block design was utilized to determine differences in embryo development and media metabolites (P ≤ 0.05). Blastocysts from oocytes matured in greater vs. lesser maturity follicular fluid had a more moderate rate of development (P = 0.01). At the conclusion of 24 h IVM, abundance of 66 metabolites differed between greater and lesser follicle maturity treatments. Nine metabolites differed in media conditioned by developing embryos. Metabolome results suggest improved amino acid, purine, and glucose metabolism, followed by a more efficient rate of embryo development, in oocytes matured in greater vs lesser maturity follicular fluid.

In older individuals, the role of low serum uric acid (SUA) as risk factor for mortality is debated. We therefore studied whether SUA levels, particularly low SUA concentrations, are associated with all-cause and cardiovascular (CV) mortality in older population, and to clarify potential effect modification of kidney function.

We identified 14,005 older people in National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018. SUA was measured only at baseline. The relationship between SUA and mortality was assessed using Cox proportional hazards models and restricted cubic spline Cox regression stratified by the estimated glomerular filtration rate (eGFR).

During mean 8.3 years of follow-up, 4852 all-cause death and 1602 CV death were recorded. A significant U-shaped association was observed between SUA with all-cause mortality, with the lowest risk concentration of 5.5 mg/dL. Comparing to the reference group (5 to 7 mg/dL), the HR of 2 to < 5 mg/dL group was 1.11 (1.03-1.21) and 1.14 (1.00-1.30). This relationship was more pronounced in participants with an eGFR ≥ 60 ml/min/1.73m2 (HR, 1.16; 95%CI, 1.06-1.28). This situation similarly occurred in Urine protein negative group (HR, 1.14; 95%CI, 1.04-1.25).

Low SUA concentrations are associated with an increased risk in all-cause and CV mortality among older participants. Extremely low SUA concentrations are especially undesirable, especially in the older adults with normal kidney function.

Elevated maternal serum uric acid (UA) levels were associated with adverse perinatal outcomes. This study aimed to examine the association between UA and the risk of low birth weight (LBW) / small for gestational age (SGA).

A cohort study of women delivered in Shanghai maternity hospital was included between 2017 and 2021. Electronic medical records were utilized to extract information and antenatal care records. The cut-off value of UA was 360 μmol/L. The outcome was LBW/SGA, with LBW defined as birth weight below 2500 g and SGA indicating birth weight below the 10th percentile of average weight for gestational age. The assessment of SGA was based on the Chinese standard curve for birth weight at various gestational ages. Univariate, multivariate logistic regression models, restricted cubic spline were used in this study, with adjustments made for confounding factors.

Sixty-nine thousand six hundred seventy-four live births and singleton pregnancies were included. The ratio of LBW/SGA was 3.3%/9%. Maternal UA levels were significantly negatively correlated with birth weight. High UA levels were associated with high risk of LBW/SGA, especially in third trimester. In BMI < 25 group, the risk of LBW increased to 2.35-fold (95%CI, 1.66-3.31) in hyperuricemic group (UA > 360 μmol/L). The SGA risk was 1.66-fold (95%CI, 1.37-2.00). Gestational hypertension (GH) with hyperuricemica increased the risk of LBW (aOR = 4.00, 95%CI, 2.01-7.93) and SGA (aOR = 2.63, 95%CI, 1.83-3.78). Preeclampsia (PE) with hyperuricemia increased the risk of LBW (aOR = 1.38, 95%CI, 0.63-3.03) and SGA (aOR = 1.81, 95%CI, 1.18-2.78). In delivery gestational week (DGW) ≥ 37 group, if UA > 360 μmol/L, the incidence of LBW increased to 2.46-fold (95%CI, 1.62, 3.73) and the incidence of SGA increased to 1.52-fold (95%CI, 1.24, 1.87). In DGW < 37 group, if UA > 360 μmol/L, the incidence of LBW increased to 2.70-fold (95%CI, 1.92, 3.80) and the incidence of SGA increased to 2.13-fold(95%CI, 1.50, 3.02).

The study found an inverse correlation between UA levels and birth weight. High UA levels were associated with increased risk of LBW/SGA, particularly in third trimester. GH or PE complicated by hyperuricemia were found to have significantly higher risk of developing LBW/SGA. This relationship also existed in pregnant women with BMI < 25.

The burden of metabolic syndrome (MetS) continues to rise globally and is associated with complications of multiple organ systems. We aimed to identify the association between changes in MetS status and accelerated renal function progression through a regional epidemiological survey in China, thus discovering influence factors with treatable potential.

This study was a population-based survey conducted in 2008 and 2014, assessing a representative sample of 5,225 individuals from rural areas of China. They were divided into four subgroups according to their MetS status in 2008 and 2014 (Never, Previously abnormal, New-onset, and Consistent). Multivariate logistic regression and stratification analysis evaluated the relationship between clinical factors and renal function decline under different MetS statuses. Smooth curve fitting further addressed the role of serum uric acid, illustrating the vital turning point of uric acid levels in the background of renal function deterioration.

Of all groups of MetS states, the new-onset MetS showed the most significant eGFR decline, with a 6.66 ± 8.21 mL/min/1.73 m2 decrease over 6 years. The population with newly-onset MetS showed a considerable risk increase in delta eGFR with a beta coefficient of 1.66 (95%CI=1.09-2.23) after necessary correction. In searching for the drivers, the strength of the association was significantly reduced after additional adjustment for uric acid levels (β=0.91, 95%CI=0.35-1.45). Regarding the turning point, uric acid levels exceeding 426 μmol/L were more significantly associated with the stepped-up deterioration of kidney function for those with new-onset MetS.

Metabolic syndrome demonstrated a solid correlation with the progression of renal function, particularly in those with newly-onset MetS status. In addition to the diagnostic components of MetS, hyperuricemia could be used as a marker to identify the high risk of accelerating eGFR decline early. Furthermore, we suggested a potential renal benefit for the newly-onset MetS population when maintaining their serum uric acid level below the criteria for asymptomatic hyperuricemia.

To analyze the relationship between the polymorphism and mutation of rs7125942 and rs3736228 locus in the low-density lipoprotein receptor-related protein 5 (LRP5) genotype and bone mineral density (BMD) in postmenopausal women in Xinjiang, China, to provide a basis for prevention and treatment of the disease.

According to the results of dual-energy X-ray (DEXA) determination of BMD, the 136 subjects were divided into three groups: Group A: normal bone mass, Group B: osteopenia, Group C: osteoporosis. 1. Age, body, mass index (BMI), and menopause of all subjects were recorded. 2. Fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and clinical biochemical data were determined. 3. LRP5 locus polymorphisms were determined by time-of-flight mass spectrometry.

1. Compared with group A, the age, ALP, Cr, and BUN levels in group B and group C were increased, but UA levels were lower (P < 0.05), and Serum P was higher in the group C (P < 0.05). 2. There was no statistically significant difference in the prevalence of diabetes between the three groups (P > 0.05). 3. The ROC curves for different BMD sites such as L1, L2, L3, L4, L total, and femoral neck were 0.929, 0.955, 0.901, 0.914, 0.885, and 0.873 (P < 0.01). 4. At rs7125942 locus, there was statistically significant difference in the distribution of wild-type (CC) and mutant (CG) with the normal bone mass (NBM) group and the abnormal bone mass (ABM) group (P < 0.05). 5. At rs7125942 locus, compared with wild-type (CC), mutant (CG) had lower LDL and FPG in NBM group (P < 0.05), and lower serum ALP in the ABM group (P < 0.05). At rs3736228 locus, the BMD (Femoral neck) of mutant (CT/TT) was lower than that of wild-type (CC) in the NBM group (P < 0.05). 6. Age and menopausal years were negatively correlated with BMD of the femoral neck and L1-4 (P < 0.05), and BMI and TG were positively (P < 0.05), and the results of multiple linear regression analysis showed that age, BMI, and TG were both independent factors affecting BMD (P < 0.05).

Previous studies have demonstrated an association between SUA and dyslipidemia. This study aims to explore the temporal relationship between SUA and dyslipidemia.

Based on the Beijing Health Management Cohort conducted from 2013 to 2018, the data of a physical examination population was collected, including a total of 6630 study subjects. Cross-lagged panel analysis was employed to examine the temporal relationship between elevated SUA levels and dyslipidemia, indicated by either elevated TG or decreased HDL-C. The path coefficient and the 95 % CI from baseline TG to follow-up SUA were as follows: in the general population, men, women, and people with BMI ≥25 kg/m2were 0.027 (0.008-0.045), 0.024 (0.001-0.048), 0.032 (0.001-0.063) and 0.033 (0.006-0.059) (P < 0.05); however, the path coefficient from baseline SUA to follow-up TG and the 95 % CI were not statistically significant. Furthermore, the path coefficients and 95 % CIs between elevated SUA and decreased HDL-C were not statistically significant, both in the general population and in populations stratified by gender and BMI.

We found a temporal relationship from elevated TG to elevated SUA in the general population and the populations stratified by gender and BMI (≥25 kg/m2). However, we did not observe a reverse relationship from elevated SUA to elevated TG. Additionally, we did not find a temporal relationship between decreased HDL-C and elevated SUA in both the general population and the stratified populations.

The relationship between diabetes mellitus (DM) and high serum uric acid is complex and controversial. Many epidemiological studies have reported a positive association, whereas others have reported an inverse association or none. In the pathogenesis of DM it is the intracellular urate that is more important than the extracellular and dissociation between the two is possible. Evidence suggests that high serum uric acid induces insulin resistance and beta cell failure in animal models. Reduction of intracellular uric acid can be achieved by dietary measures such as reducing fructose and salt intake, and uric acid-lowering drugs. We suggest that in the Western diet, these elements play a crucial role in pathogenesis of DM. To determine the precise and exact interrelationship between intracellular and extracellular uric acid, well-designed studies are required. Besides this, clinical trials are needed to determine whether intracellular and extracellular urate reduction will provide benefit in prevention and treatment of DM and complications associated with it.

Serum uric acid (UA), as an antioxidant, has been associated with hypertension in the general population. Hypertension is highly prevalent in patients with polymyositis and dermatomyositis (PM/DM). Owning elevated levels of reactive oxygen species, patients with PM/DM have lower concentrations of UA in comparison with healthy people. We explored a potential association between UA levels and hypertension in PM/DM and evaluated whether this association is independent of hypertension risk factors, PM/DM characteristics and relevant drugs. A total of 472 PM/DM patients were assessed. UA and related laboratory data were measured. Demographic, hypertension-related factors, PM/DM characteristics and drug use were assessed as potential covariates. Results were analyzed using logistic models to test the independence of the association between UA and hypertension. UA levels were higher in hypertension subjects compared to non-hypertensive PM/DM patients [284.70 (239.93-357.38) vs 264.00(222.50-322.75), p = .017]. When adjusted for hypertension risk factors, PM/DM characteristics and drugs, the odds of being a hypertensive PM/DM patient per 1 μmol/L UA increase were significantly increased: odds ratio = 1.473 (95% confidence interval:1.063-2.042, p = .020). This cross-sectional study suggests that UA levels are independently associated with hypertension in PM/DM patients.

The clinical outcome of obstructive sleep apnea in patients with acute coronary syndrome in relation to hyperuricemia is still unclear. We aimed to explore the clinical prognosis of obstructive sleep apnea in patients with acute coronary syndrome in relation to hyperuricemia status. This was a prospective cohort study. We included consecutively eligible patients with acute coronary syndrome who underwent cardiorespiratory polygraphy between June 2015 and January 2020. According to apnea-hypopnea index ≥ 15 events per hr and serum uric acid level, the population was divided into four groups: hyperuricemia with obstructive sleep apnea; hyperuricemia with non-obstructive sleep apnea; no hyperuricemia with obstructive sleep apnea; and no hyperuricemia with non-obstructive sleep apnea. The primary endpoint was major adverse cardiovascular and cerebrovascular events, including cardiovascular death, myocardial infarction, stroke, ischaemia-driven revascularization, and readmission for unstable angina or heart failure. Spearman correlation analysis and Cox regression model were mainly used to estimate the data. The median follow-up was 2.9 years. Among 1925 patients with acute coronary syndrome, 29.6% had hyperuricemia and 52.6% had obstructive sleep apnea. Uric acid was negatively correlated with minimum arterial oxygen saturation and mean arterial oxygen saturation, and positively correlated with apnea-hypopnea index, oxygen desaturation index and the duration of time with arterial oxygen saturation < 90% (p < 0.001). During 2.9 (1.5, 3.6) years of follow-up, obstructive sleep apnea was associated with an increased risk of major adverse cardiovascular and cerebrovascular events in patients with hyperuricemia (23.5% versus 13.4%; adjusted hazard ratio: 1.834; 95% confidence interval: 1.192-2.821, p = 0.006), but not in patients without hyperuricemia (21.9% versus 19.2%; adjusted hazard ratio: 1.131; 95% confidence interval: 0.880-1.453, p = 0.336). There was a correlation between uric acid levels and sleep respiratory indicators. Obstructive sleep apnea was associated with increased risk of major adverse cardiovascular and cerebrovascular events in patients with acute coronary syndrome with hyperuricemia, but not in patients without hyperuricemia.

The fructose survival hypothesis proposes that obesity and metabolic disorders may have developed from over-stimulation of an evolutionary-based biologic response (survival switch) that aims to protect animals in advance of crisis. The response is characterized by hunger, thirst, foraging, weight gain, fat accumulation, insulin resistance, systemic inflammation and increased blood pressure. The process is initiated by the ingestion of fructose or by stimulating endogenous fructose production via the polyol pathway. Unlike other nutrients, fructose reduces the active energy (adenosine triphosphate) in the cell, while blocking its regeneration from fat stores. This is mediated by intracellular uric acid, mitochondrial oxidative stress, the inhibition of AMP kinase and stimulation of vasopressin. Mitochondrial oxidative phosphorylation is suppressed, and glycolysis stimulated. While this response is aimed to be modest and short-lived, the response in humans is exaggerated due to gain of 'thrifty genes' coupled with a western diet rich in foods that contain or generate fructose. We propose excessive fructose metabolism not only explains obesity but the epidemics of diabetes, hypertension, non-alcoholic fatty liver disease, obesity-associated cancers, vascular and Alzheimer's dementia, and even ageing. Moreover, the hypothesis unites current hypotheses on obesity. Reducing activation and/or blocking this pathway and stimulating mitochondrial regeneration may benefit health-span. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

Atherosclerosis is one of the most fatal diseases in the world. The associated thickening of the arterial wall and its background and consequences make it a very composite disease entity with many mechanisms that lead to its creation. It is an active process, and scientists from various branches are engaged in research, including molecular biologists, cardiologists, and immunologists. This review summarizes the available information on the pathophysiological implications of atherosclerosis, focusing on endothelium dysfunction, inflammatory factors, aging, and uric acid, vitamin D, and miRNA expression as recent evidence of interactions of the molecular and cellular elements. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of cardiovascular diseases.

The aim of this study was to explore the relationship between serum uric acid (SUA) and the triglyceride-glucose (TyG) index, which is a more effective indicator of insulin resistance. The study participants included 1700 children and adolescents with short stature who were recruited at the Affiliated Hospital of Jining Medical University in China between March 2013 and April 2021. A positive association between SUA levels and the TyG index was detected by univariate analysis (p < 0.001). Furthermore, a nonlinear relationship was detected between SUA and the TyG index, whose point was 6.55 mg/dL. There was a positive association between SUA and the TyG index when the SUA level was greater than 6.55 mg/dL (β 0.17, 95% CI: 0.07, 0.27; P < 0.001). However, we did not observe a significant relationship between SUA and the TyG index when the SUA level was less than 6.55 mg/dL (β 0.02, 95% CI: - 0.01, 0.05; P = 0.091). In addition, a stratified analysis was performed to appraise changes in this relationship for different sexes. The relationship between SUA and the TyG index in males and females is consistent with that in the general population, showing a nonlinear relationship. However, the inflection points of SUA level were significantly higher in males than in females, and the inflection points were approximately 6.72 and 5.88 mg/dL, respectively. This study revealed a nonlinear relationship between SUA and the TyG index in children with short stature. The nonlinear relationship remained in gender stratification analysis, but the inflection point of SUA level was higher in men. Further studies are needed to establish a causal relationship between SUA levels and the TyG index in children with short stature.

The molecular mechanisms underlying uric acid (UA)-induced mitochondrial dysfunction and apoptosis have not yet been elucidated. Herein, we investigated underlying mechanisms of UA in the development of mitochondrial dysfunction and apoptosis. We analyzed blood samples of individuals with normal UA levels and patients with hyperuricemia. Results showed that patients with hyperuricemia had significantly elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, which may indicate liver or mitochondrial damage in patients with hyperuricemia. Subsequently, lipidomic analysis of mouse liver tissue mitochondria and human liver L02 cell mitochondria was performed. Compared with control group levels, high UA increased mitochondrial phosphatidylserine (PS) and decreased mitochondrial phosphatidylethanolamine (PE) levels, whereas the expression of mitochondrial phosphatidylserine decarboxylase (PISD) that mediates PS and PE conversion was downregulated. High UA levels also inhibited signal transducer and activator of transcription 3 （STAT3） phosphorylation as well as mitochondrial respiration, while inducing apoptosis both in vivo and in vitro. Treatment with allopurinol, overexpression of PISD, and lyso-PE (LPE) administration significantly attenuated the three above-described effects in vitro. In conclusion, UA may induce mitochondrial dysfunction and apoptosis through mitochondrial PISD downregulation. This study provides a new perspective on liver damage caused by hyperuricemia.

Despite its discovery more than 150 years ago, the cause of primary hypertension remains unknown. Most studies suggest that hypertension involves genetic, congenital or acquired risk factors that result in a relative inability of the kidney to excrete salt (sodium chloride) in the kidneys. Here we review recent studies that suggest there may be two phases, with an initial phase driven by renal vasoconstriction that causes low-grade ischemia to the kidney, followed by the infiltration of immune cells that leads to a local autoimmune reaction that maintains the renal vasoconstriction. Evidence suggests that multiple mechanisms could trigger the initial renal vasoconstriction, but one way may involve fructose that is provided in the diet (such as from table sugar or high fructose corn syrup) or produced endogenously. The fructose metabolism increases intracellular uric acid, which recruits NADPH oxidase to the mitochondria while inhibiting AMP-activated protein kinase. A drop in intracellular ATP level occurs, triggering a survival response. Leptin levels rise, triggering activation of the sympathetic central nervous system, while vasopressin levels rise, causing vasoconstriction in its own right and stimulating aldosterone production via the vasopressin 1b receptor. Low-grade renal injury and autoimmune-mediated inflammation occur. High-salt diets can amplify this process by raising osmolality and triggering more fructose production. Thus, primary hypertension may result from the overactivation of a survival response triggered by fructose metabolism. Restricting salt and sugar and hydrating with ample water may be helpful in the prevention of primary hypertension.

Cardiovascular diseases (CVDs) are the leading cause of mortality and disability among both males and females. The risk of cardiovascular diseases is heightened by the presence of a risk factor cluster of metabolic syndrome, covering obesity and obesity-related cardiometabolic risk factors such as hypertension, glucose, and lipid metabolism dysregulation primarily. Sex hormones contribute to metabolic regulation and make women and men susceptible to obesity development in a different manner, which necessitates sex-specific management. Identifying crucial factors that protect the cardiovascular system is essential to enhance primary and secondary prevention of cardiovascular diseases and should be explicitly studied from the perspective of sex differences. It seems that AMP-dependent protein kinase (AMPK) may be such a factor since it has the protective role of AMPK in the cardiovascular system, has anti-diabetic properties, and is regulated by sex hormones. Those findings highlight the potential cardiometabolic benefits of AMPK, making it an essential factor to consider. Here, we review information about the cross-talk between AMPK and sex hormones as a critical point in cardiometabolic disease development and progression and a target for therapeutic intervention in human disease.

The impact of elevated serum uric acid levels i.e., hyperuricemia, on native and transplant chronic kidney disease progression has been debated. This literature review presents an analysis of multiple studies exploring the relationship between serum uric acid levels and kidney transplant outcomes. The review includes a summary of the pathophysiology of hyperuricemia and gout, a review of urate-lowering therapies, and an appraisal of multiple studies examining the association or lack thereof between serum uric acid level and kidney transplant outcomes. Based on these studies, elevated serum uric acid levels may contribute to CKD progression in kidney transplant recipients. In this review, we also summarize current literature to highlight risk factors associated with hyperuricemia as well as the need for further investigation to monitor and manage hyperuricemia in kidney transplant recipients.