The association between serum uric acid levels and peripheral vertigo diseases, namely Benign Paroxysmal Positional Vertigo (BPPV), Meniere's Disease (MD), and Vestibular Neuritis (VN), remains a subject of controversy. This study utilises the Mendelian Randomization (MR) approach to investigate the potential link between uric acid levels and these peripheral vertigo diseases, with the goal of informing preventative measures and early intervention strategies.

Datasets pertaining to uric acid levels (sample size = 343 836) and BPPV (ncase = 3834, ncontrol = 209 582), MD (ncase = 1511, ncontrol = 209 582), and VN (ncase = 1224, ncontrol = 209 582) were selected from Genome-Wide Association Studies (GWAS). Two-sample MR was employed to analyse the correlation between the exposure (uric acid levels) and outcomes (BPPV, MD, VN). The MR analysis methods encompassed Inverse Variance Weighting (IVW), MR-Egger, Simple Mode, Weighted Mode, and Weighted Median methods. The results derived from the IVW analysis were considered as the primary analytical outcomes.

The findings indicated no significant correlation between uric acid levels and BPPV (IVW: OR = 1.152, 95% CI: 0.971-1.367, p = 0.103), MD (IVW: OR = 1.010, 95% CI: 0.757-1.348, p = 0.943), and VN (IVW: OR = 1.005, 95% CI: 0.744-1.358, p = 0.969).

This study employed a two-sample Mendelian randomization approach to conduct an in-depth analysis of the relationship between serum uric acid levels and peripheral vestibular diseases (BPPV, MD, and VN). Our findings indicate that no significant association was found between serum uric acid levels and these diseases. The results of the study do not support the hypothesis that uric acid is an independent risk factor for these conditions.

Maintaining polyamines homeostasis is essential for cardiovascular health, whereas elevated uric acid levels are recognized as a significant risk factor for the onset and progression of cardiovascular diseases. However, the interaction between uric acid and the regulation of polyamine homeostasis has not been extensively investigated. The objective of this study was to investigate the influence of uric acid on cardiac polyamines regulation and elucidate the role of polyamines in uric acid induced cardiomyocytic injury.

The in vitro experiments utilized H9C2 cardiomyocytes, the hyperuricemic mouse model was established via potassium oxonate and hypoxanthine. Techniques included energy metabolomics, HPLC for polyamine quantification, qPCR, ELISA, immunofluorescence, and mitochondrial membrane potential assessment using JC-1 staining, MTT cell viability analysis.

Uric acid treatment can alter ornithine metabolism in cardiomyocytes, revealed a potential of shifting it from the traditional ornithine cycle towards the polyamine cycle. Both ODC1 and SAT1 protein levels were up-regulated in hyperuricemic mice indicated a dysorder of polyamines homostasis. A downregulation tendency of spermidine and spermine levels were observed in cardiomyocytes under uric acid treatment. Notably, exogenous supplementation with spermidine or spermine effectively mitigated the uric acid-induced decline in cardiomyocyte viability and mitochondrial membrane potential.

Uric acid disrupts polyamine homeostasis, leading to mitochondrial dysfunction and cardiomyocyte damage. Exogenous polyamine supplementation demonstrates therapeutic potential by preserving mitochondrial integrity. These findings unveil a potential mechanism underlying uric acid-induced cardiac injury and propose polyamine replenishment as a viable intervention strategy for hyperuricemia-related cardiovascular complications.

Background: Diabetic ketoacidosis (DKA) is a life-threatening complication commonly seen in Type 1 diabetes mellitus (T1DM) but also affects Type 2 diabetes mellitus (T2DM). Objectives: To compare the clinical presentation, biochemical parameters, and precipitating factors of DKA in adult patients with T1DM and T2DM. Methodology: This retrospective cohort study was conducted at King Salman Hospital, Riyadh, involving medical records of diabetic patients aged 14 years or older who attended the Diabetic Center from September 1, 2021, to August 1, 2022. Data collection included sociodemographic, clinical, biochemical, and management details using a standardized checklist. Results: The study included 285 patients with DKA, aged 14-70 years (mean: 23.1 ± 11.5 years), with 52.5% being male. The most common symptoms were nausea (91.1%), abdominal pain (86.1%), vomiting (83.6%), polyuria/polydipsia (74.1%), and shortness of breath (72.4%). Vomiting and abdominal pain were more frequent in T1DM (85.9% and 88.3%) compared to T2DM (65.6% and 68.8%), p=0.004 and 0.003, respectively, while dizziness was more common in T2DM (56.3% vs. 33.2%), p=0.011. Uric acid and creatinine levels were significantly higher in T2DM, whereas hemoglobin and hematocrit were elevated in T1DM. Poor compliance was the most common precipitating factor (70.2%), followed by upper respiratory tract infection (21.1%) and inadequate treatment (15.6%). Conclusion: This study highlights key differences in DKA presentation between T1DM and T2DM. While symptoms such as nausea and abdominal pain were common in both types, vomiting was more frequent in T1DM and dizziness in T2DM. Biochemical markers such as uric acid and creatinine were elevated in T2DM, while hemoglobin and hematocrit were higher in T1DM. Poor compliance was a more common precipitating factor in T1DM, whereas inadequate treatment prevailed in T2DM. Tailored management approaches for each diabetes type may improve DKA outcomes.

Protein S-nitrosylation (SNO), a redox-based posttranslational modification of cysteine thiols, plays a crucial role in various signaling pathways. Peroxiredoxin 2 (PRDX2) is one of the most potent ROS scavenging proteins, providing protection against oxidative stress damage, with its function regulated by SNO. However, the precise role of SNO-PRDX2 in hyperuricemic nephropathy remains poorly understood. In this study, we identified PRDX2 as a highly S-nitrosylated target in hyperuricemic nephropathy using a biotin switch assay. The elevation of SNO-PRDX2 was observed in kidneys of hyperuricemic mice as well as in uric acid (UA)-treated human renal tubular epithelial (HK-2) cells. S-nitrosoglutathione (GSNO), an endogenous nitric oxide carrier, induced SNO modification of PRDX2, promoting mitochondrial dysfunction, oxidative stress, and cell apoptosis in HK-2 cells. Transfection with a plasmid containing a mutated cysteine 172 (Cys172) of PRDX2 yielded a decrease in SNO-PRDX2 levels in both hyperuricemic mice and UA-cultured HK-2 cells. Furthermore, administration of adeno-associated viruses carrying the Cys172-mutated PRDX2 significantly ameliorated renal interstitial fibrosis and reduced mitochondrial dysfunction, oxidative stress, and cell apoptosis in HUA-treated mice. In conclusion, our findings indicate that SNO modification of PRDX2 at Cys172 mediates HUA-induced kidney interstitial fibrosis, suggesting that SNO-PRDX2 may serve as a potential therapeutic target for HUA-induced renal injury.

Although hyperuricemia is associated with chronic kidney disease (CKD), the impact of uric acid (UA)-lowering drugs on CKD has been controversial. Previous investigations have primarily included xanthine oxidase inhibitors; therefore, research of dotinurad, a recently developed selective urate reabsorption inhibitor, is necessary. This retrospective study included 58 patients with CKD; of these, 29 newly initiated dotinurad and 29 initiated febuxostat. The effects of dotinurad and febuxostat on the serum UA, urinary UA-to-creatinine ratio (UUCR), and estimated glomerular filtration rate (eGFR) during 3 months were analyzed to compare their impacts on renal function. Dotinurad and febuxostat decreased serum UA (8.40 ± 1.11 to 6.50 ± 0.80 mg/dL [p < 0.001] and 8.91 ± 1.21 to 6.05 ± 1.28 mg/dL [p = < 0.001], respectively). The UUCR increased after dotinurad (0.35 ± 0.15 to 0.40 ± 0.21 g/gCr [p = 0.024]); however, it decreased after febuxostat (0.33 ± 0.12 to 0.21 ± 0.06 g/gCr [p = 0.002]). The eGFR improved after dotinurad (33.9 ± 15.2 to 36.2 ± 15.9 mL/min/1.73 m2 [p < 0.001]). No change was observed after febuxostat treatment (33.4 ± 19.6 to 34.1 ± 21.6 mL/min/1.73 m2). Renal function improved only with dotinurad, thus highlighting its renoprotective effects beyond the reduction of serum UA.

Due to the intense demand for low-cost, environmentally friendly, and stable uric acid (UA) detection methods, a novel biosensing nanosystem made with marine diatom was studied. Reduced by live diatom (Thalassiosira pseudonana), metallic nanoparticles (CuX) were hybridized with the heteronanostructure (Diatom frustule, DF), showing peroxidase activity 2.66-fold over horseradish peroxidase (HRP). To immobilize the enzyme directionally with increasing loading amounts, silaffin peptides (R5 and T8) were designed for tagging the urate oxidase (UoX). The enzyme loading on DF of tagged UoX was 1.76-fold (R5) and 1.54-fold (T8) that of untagged UoX. The activity of immobilized UoX-R5 was 5.29-11.76-fold more than that of free UoX-R5 at various pH levels (5-10) and temperatures (20-60 °C). The nanosystem (UoX-R5 immobilized on CuX-coated diatom frustules, termed as BioHNS) demonstrated a superior linear range of 5 × 10-6 to 1 × 10-3 M and a detection limit of 1.6 μM, surpassing the performance of the majority of reported UA sensors. The recoveries of UA in urine were detected by the BioHNS, ranging from 96.93 to 105.35%, with a relative deviation of less than 5.00%. The BioHNS showed excellent anti-interference and storage stability (2 months). In summary, BioHNS demonstrates significant potential as a sustainable and environmentally friendly biosensor for uric acid detection, highlighting its substantial relevance to the biomedical applications of marine diatoms.

We aimed to examine the impact of gout on cardiovascular disease (CVD) and mortality risk in patients with type 2 diabetes and explore whether chronic kidney disease (CKD) modifies this association.

Using the Korean National Health Insurance Service database, 757 378 individuals with type 2 diabetes were classified into the CKD-Gout-, CKD-Gout+, CKD+Gout-, and CKD+Gout+ groups. Cox proportional hazard models were used to assess the risk of myocardial infarction (MI), ischemic stroke, and mortality, after adjusting for cardiometabolic factors.

Over a median follow-up of 9.3 years, 25 618, 38 691, and 78 628 individuals experienced MI, stroke, and mortality, respectively. The risk of MI or stroke progressively increased across the groups, with the highest adjusted hazard ratio (HR) in the CKD+Gout+ group (HR: 1.57, 95% confidence interval [CI]: 1.46-1.69), followed by the CKD+Gout- group (HR: 1.23, 95% CI 1.20-1.26). The CKD+Gout+ group showed the greatest risks for MI (HR: 1.71), stroke (HR: 1.46), and mortality (HR: 1.78). Individuals with gout alone did not exhibit a significant increase in risk compared with those without gout or CKD. Interaction analyses indicated that the effect of gout on the outcomes was more pronounced in patients with CKD. Subgroup analyses yielded consistent findings across diverse demographic and clinical characteristics.

CKD with or without gout increased the risk of CVD and mortality, with the highest risk observed in the CKD+Gout+ group. The interaction between CKD and gout significantly influenced these outcomes.

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.

It has been shown that multiple metals exposure is associated with hyperuricemia. However, previous studies on the association and interaction between multiple metals exposure and hyperuricemia have been controversial, and there has been little evaluation of the potential mediating role of estimating glomerular filtration rate (eGFR).

In this study, levels of 12 metals in the urine of 3756 study participants were measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The associations between urinary metals and the hyperuricemia were analyzed by multivariable logistic regression model and restricted cubic spline (RCS). Weighted Quantile Sum (WQS) regression was used to explore the weight of each metal. Bayesian Kernel Machine Regression (BKMR) was used to explore the join effect of mixed metal exposure. Mediation analysis was used to explore the role of eGFR in relationship between urinary metal concentration and hyperuricemia.

In the multi-metal model, the multivariate-adjusted odds ratio (OR) and 95 % confidence interval (CI) of hyperuricemia were 0.89 (0.81,0.99) for Fe, 0.79 (0.70,0.89) for Se, 0.84 (0.75,0.93) for Cd, 0.87 (0.79,0.96) for Pb, 1.36 (1.23,1.51) for Zn (all P < 0.05). The RCS regression indicated signification nonlinear associations for Zn and Pb (all P-non-linear <0.05). The WQS regression model based on the negative fit showed that the maximum weight of Cd is 43.1 %. In the BKMR model, metal mixtures showed an overall negative association with the risk of developing hyperuricemia, and we also found interactions between Zn and Pb. Mediation analysis showed that eGFR mediated the association between Fe, Se, Cd, Pb and hyperuricemia with mediation ratios of 11.18 %, 12.10 %, 9.60 %, and 12.01 %, respectively.

The metal mixture in urine is negatively correlated with hyperuricemia, with Cd having the greatest impact. eGFR may play a partial role in association of Fe, Se, Cd and Pb exposure with hyperuricemia.

Disturbances in calcium and phosphorus homeostasis resulting from chronic kidney disease (CKD) may lead to atherosclerotic changes in blood vessels, potentially altering bone marrow perfusion. Our study aimed to investigate vertebral bone marrow perfusion using dynamic contrast-enhanced (DCE) MRI with a pharmacokinetic model. We also measured possible changes in water and fat content and bony trabeculae using T2* quantification, MR spectroscopy (MRS), and microcomputed tomography (μCT).

Twelve rats were randomly separated into a normal control group and a CKD (5/6 nephrectomy) group. Their lumbar spines were imaged, with monitoring of the L5 vertebral body conducted at 0, 8, 16, 30, and 43 weeks. After Week 43, all rats were sacrificed, and histologic changes were correlated with MRI and μCT results.

The CKD group demonstrated significantly lower A and k el values (p < 0.05), significantly increased T2* values (p < 0.05), significantly decreased fat content and trabeculation (p < 0.05), sinusoidal dilatation, and decreased adipocytes in the vertebral bone marrow.

Using quantitative MRI and μCT to assess CKD-related arthropathy of the vertebral body is feasible. Lumbar spine bone marrow perfusion deficiency in experimental CKD may be associated with decreased fat content, increased water content, and sparse trabeculation.

Observational studies have linked uric acid (UA) levels and kidney disease to amino acid homeostasis, but the causal relationship is unclear. This study aims to determine if elevated UA affects amino acid levels and whether amino acids mediate this relationship, focusing on the causal links between UA, circulating amino acids, and kidney disease.

This study utilized Uox-KO mice as a hyperuricemia model, assessed renal injury through blood biochemistry and pathology, analyzed serum amino acid changes via targeted amino acidomics, and employed Mendelian randomization to investigate the causal links between uric acid, amino acids, and renal disease.

Hyperuricemia Uox-KO mice have significantly higher serum UA and renal impairment markers, with histopathological analysis showing extensive renal tissue damage. Changes in amino acid balance were found in the mice's serum, with key metabolites like alanine, isoleucine, leucine, aspartic acid, cysteine, glutamate, and glycine potentially influencing UA pathophysiology. Genetically predicted UA was positively correlated with chronic renal failure (CRF) and blood urea nitrogen(BUN) levels and negatively with serum cystatin C (eGFRcys) and serum creatinine (eGFRcrea). Alanine (Ala) mediated the effect of UA on elevated CRF and BUN risk, accounting for 4.5% of the UA-CRF relationship and 14.4% of the UA-BUN association.

In hyperuricemia mice, serum amino acids undergo metabolic changes. Genetically predicted UA levels are positively linked to CRF and BUN, but negatively linked to eGFRcys and eGFRcrea. Ala mediates UA's effect on CRF and BUN risk, indicating Ala could be a target for preventing renal diseases caused by hyperuricemia.

Insulin resistance (IR) and serum uric acid (SUA) are closely interconnected: SUA contributes to adversely affects the insulin signaling pathway and contributes to IR, while IR is a known predictor for the development of hyperuricemia. The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been proposed as an easily obtainable marker for IR. This research aimed to investigate the interaction between IR and glomerular filtration rate (GFR)-adjusted uricemia (SUA/GFR ratio) in determining CV risk in a large population cohort study.

Data from 18,694 subjects were analyzed from Uric acid Right foR heArt Healt (URRAH) database. The study evaluated the association between TG/HDL-C ratio and SUA/GFR ratio, as well as their impact on the development of outcomes during the follow-up study period. The primary endpoint was CV mortality.

After a mean follow-up of 124 ± 64 months, 2,665 (14.2%) CV deaths occurred. The incidence of fatal and non-fatal CV events increased in parallel with the increase of TG/HDL-C quintiles. TG/HDL-C ratio showed a positive association with increasing of SUA/GFR ratio, even in non-diabetic patients. Multivariate analysis showed that the TG/HDL-C ratio increases the mortality risk even after adjustment for potential confounding factors. Finally, IR and GFR-adjusted hyperuricemia showed an additive effect on CV mortality.

Both IR and SUA/GFR ratio independently predict CV mortality, regardless of age, gender, BMI, diabetes, hypertension and statin use. The joint effect of the TG/HDL-C ratio and the elevated SUA/GFR ratio was greater than the presence of each single risk factor on CV mortality. This highlights the importance of monitoring these markers to better assess cardiovascular risk.

Metabolic processes in living organisms depend on the synergistic actions of enzymes working in proximity and in concert, catalyzing reactions effectively while regulating the formation of metabolites. This enzyme synergy offers promising therapeutic application for diseases such as alcohol intoxication, cancer, and hyperinflammation. Despite their potential, the clinical translation of enzyme cascades is restricted by challenges including poor enzyme stability, short half-life, and a lack of delivery strategies that maintain enzyme proximity. In this study, multi-enzyme nanocascades synthesized are developed through in situ atom transfer radical polymerization using a zwitterionic monomer. This method markedly enhances enzyme stability and proximity, thereby prolonging their circulation half-life after systemic administration. It is demonstrated that the nanocascades of uricase and catalase effectively reduce uric acid levels without excessive hydrogen peroxide production, providing a potential antidote for hyperuricemia. Moreover, in a murine breast cancer model, the nanocascades of glucose oxidase and catalase inhibited tumor progression and enhanced the therapeutic efficacy of doxorubicin. The prolonged circulation and promoted reaction efficacy of these nanocascades underscore their substantial potential in enzyme replacement therapy and the treatment of various diseases.

To analyse the associations between renal function and clinical laboratory indicators and explore the renal function abnormality risk factors for gout patients in Southwest China.

Outpatient and hospitalized gout patients (n = 4384) at the First Affiliated Hospital of Chengdu Medical College between January 2017 and December 2020 were divided into normal (n = 2393) and abnormal (n = 1991) renal function groups according to their eGFR. The relationships between clinical laboratory indicators and the eGFR were analysed, and a logistic regression model was fit to identify significant risk factors.

Sex, age, absolute lymphocyte count (ALC), cystatin C (CysC), homocysteine (Hcy) and thyroid stimulating hormone (TSH) were associated with renal function abnormalities (P < 0.05), whereas age [odds ratio (95% CI) = 1.06 (1.05-1.08), P < 0.001], Hcy [1.02 (1.00-1.04), P = 0.028], CysC [1.72 (1.54-1.92), P < 0.001], ALC [0.71 (0.52-0.97), P = 0.03] and TSH [1.08 (1.00-1.17), P = 0.049] were abnormal renal function risk factors for gout patients. After stratification by UA, binary logistic regression analysis identified the following risk factors: Q1 age [1.06 (1.02-1.11), P = 0.003], CysC [1.67 (1.30-2.16), P < 0.001]; Q2 age [1.09 (1.06-1.12), P < 0.001], CysC [1.55 (1.28-1.88), P < 0.001], FT3 [0.66 (0.46-0.96), P = 0.029]; Q3 age [1.06 (1.03-1.09), P < 0.001], CysC [1.75 (1.41-2.18), P < 0.001], Hcy [1.04 (1.00-1.08), P = 0.047], ALC [0.35 (0.18-0.69), P = 0.002]; Q4 age [1.05 (1.02-1.09), P = 0.004], CysC [1.79 (1.40-2.30), P < 0.001].

ALC and levels of TSH and serum Cys could be used for monitoring for abnormal renal function in patients with gout.

Gout is the most common form of inflammatory arthritis, caused by the deposition of monosodium urate crystals in the joints due to elevated serum uric acid levels. Its prevalence and associated healthcare burden have been rising in recent decades, a trend expected to continue. It is crucial to recognize that gout and hyperuricemia are not merely causes of painful joint flares, but systemic metabolic disorders linked to a broad spectrum of comorbidities such as cardiovascular diseases, chronic kidney disease, diabetes, insulin resistance, steatotic liver disease, osteoarthritis, and respiratory and eye diseases. Numerous risk factors for gout and hyperuricemia have been identified, with recent research uncovering further associations with other conditions. To optimize patient outcomes, gout and hyperuricemia must be addressed through a holistic approach that accounts for these risk factors while providing comprehensive management of related comorbidities affecting various organ systems. This review summarizes the current knowledge on the risk factors, comorbidities, and clinical implications of gout and hyperuricemia. Future research should focus on improving patient outcomes by tailoring treatments individually and addressing the underlying metabolic comorbidities of gout with multimodal treatment.

Preeclampsia (PE) is a common complication of pregnancy that carries significant risks for both the mother and the fetus, and is frequently accompanied by hyperuricemia, yet the exact source of elevated uric acid (UA) levels remains partially elucidated. Several potential origins for increased UA levels include abnormal renal function, increased tissue breakdown, and increased activity of the enzyme Xanthine Oxidase (XO). The aim of the study was to determine serum levels of UA and XO not only in maternal serum, but also in umbilical vein (UV) and umbilical artery (UA) and explore their possible role in PE development.

A prospective case-control pilot study was conducted in women who were found positive for PE with severe features, and had elevated UA levels above 6 mg/dL, with normotensive pregnant women serving as controls. Renal function, UA and XO levels were measured in maternal, UV and UA serums immediately after delivery. They were then compared between PE (n = 21) and control (n = 18) groups, as well as across all mediums (maternal, UV and UA) among the total study sample (N = 39). Diastolic blood pressure (DBP) was also measured immediately following delivery.

The mean serum maternal creatinine levels did not differ significantly between groups (0.65 ± 0.03 vs 0.6 ± 0.07, p = 0.13). Both mean maternal serum UA and XO concentrations were higher in PE group than in control (7.3 ± 1.2 vs 4.2 ± 0.9, p < 0.01 and 3.6 ± 3.5 Vs 1.7 ± 0.8, p < 0.01, respectively). The mean UV and UA serum XO concentrations were significantly higher in PE group compared to control (4.2 ± 3.6 vs 2.2 ± 1.4, p < 0.01 and 4.2 ± 3.6 vs 2.1 ± 1.5, p < 0.01, respectively). Polynomial fit correlation test demonstrated a significant association between maternal DBP and UV XO concentration for all the total study participants (p = 0.03).

Despite preserved renal functions, UA and XO levels were elevated in women with PE. Importantly, this pattern was found to be applied to the feto-placental unit as well, which may indicate an active involvement of the fetus in the hypoxic process. Further study is needed to clarify the possible role of the feto-placental unit in pregnancies complicated by PE.

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 compare the performance of the 2016 preliminary gout remission definition and a simplified gout remission definition in a clinical trial of nurse-led gout care.

Data from a 2-year parallel arm, non-blinded, randomised controlled trial of 517 community-derived people with gout were analyzed. Participants were assigned 1:1 to receive nurse-led care or general practitioner usual care. Remission was defined using the 2016 preliminary gout remission definition and a simplified gout remission definition without patient reported outcomes. Binary logistic regression was used to compare intervention groups. General linear models were used to compare Gout Impact Scale (GIS) scores between those in remission and those not in remission using either definition.

Participants in the nurse-led care group were more likely to achieve remission using either definition; at Year 2 the odds ratio was 7.92 [95 % CI 4.86-12.92] using the 2016 preliminary definition and 11.88 [95 % CI 7.49-18.84] using the simplified definition. For all participants, the 2016 preliminary definition was fulfilled by 9.9 % at Year 1 and 28.4 % at Year 2, p < 0.001 and the simplified definition was fulfilled by 17.6 % at Year 1 and 42.7 % at Year 2, p < 0.001. People in remission using either definition had better gout outcomes assessed using the GIS, including greater control over their gout.

Both definitions discriminated between the intervention groups and showed high construct validity. The simplified definition identified more people as being in gout remission at Year 1 and Year 2. The simplified definition is a feasible and valid option for defining gout remission.

Background/Objectives: The accurate prediction of postoperative renal function (post-RF) in living kidney donors is essential for optimizing donor safety and long-term health. After nephrectomy, renal function can be significantly altered, owing to the functional adaptation of the remaining kidney; however, the extent of this has not been investigated. This study aimed to examine how various donor factors affect functional adaptation after nephrectomy, and to develop a new predictive model. Methods: In total, 310 patients who underwent donor nephrectomy were included. Preoperative split renal function (pre-SRF) of the remaining kidney was measured. Post-RF was measured 1 month after surgery. The functional adaptation rate was calculated from the difference between pre-SRF and post-RF. Multiple regression analysis was performed to develop a predictive formula for post-RF, incorporating donor age and pre-SRF. Results: The median age of the donors was 60 years, and 38.7% were men. The median pre-SRF was 36.4 mL/min/1.73 m2. The median functional adaptation rate was 26.8%, with donor age, pre-SRF, and a history of hyperuricemia (HUA) being significant predictors of the functional adaptation rate. The equation for post-RF was established as 0.94 × pre-SRF - 0.12 × age + 18.87 mL/min/1.73 m2. The estimated post-RF showed a high coefficient of determination (R2 = 0.76), with a mean bias of -0.01 mL/min/1.73 m2. Conclusions: Donor age, pre-SRF, and HUA are key predictors of renal functional adaptation after nephrectomy. The developed formula accurately estimates post-RF, supporting clinical decision-making and donor counseling for living kidney donations.

Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. Urate, known for its antioxidant properties, may influence CRC risk and prognosis, but research on this is limited. We used Mendelian randomization (MR) analysis to explore the causal relationship between serum urate levels and CRC risk. Additionally, we analyzed National Health and Nutrition Examination Survey data to assess the impact of serum urate on CRC prognosis. MR analysis in the European population indicated that higher serum urate levels are associated with a reduced CRC risk (odds ratios [OR] inverse-variance weighted: 0.90, 95% CI: 0.81-0.99, P = .04; OR MR-Egger: 0.86, 95% CI: 0.75-0.98, P = .03; OR Weighted-Median: 0.85, 95% CI: 0.74-0.96, P = .01; OR Weighted-Mode: 0.83, 95% CI: 0.74-0.94, P = .002). Validation datasets supported this (OR inverse-variance weighted: 0.83, 95% CI: 0.72-0.96, P = .011). However, National Health and Nutrition Examination Survey data showed that higher serum urate levels are linked to poorer CRC outcomes (HR 1.50, 95% CI: 1.08-2.10, P = .02). This study suggests that elevated serum urate levels may reduce CRC risk but are associated with worse prognosis in CRC patients, highlighting its potential as a biomarker for CRC risk and prognosis.

The causal link between serum uric acid (SUA) levels and gastric cancer susceptibility remains inadequately elucidated. This investigation employed a two-sample Mendelian randomization (MR) framework to assess the potential causative link between SUA concentrations and the propensity for developing gastric cancer. To further explore potential racial differences, this MR analysis was conducted on cohorts of both European and East Asian descent. Data from a large-scale GWAS in 343,836 Europeans and 92,615 East Asians were screened for 206 and 45 SNPs significantly linked to SUA levels, respectively, as genetic variants. Subsequently, four distinct MR methodologies were deployed to determine how SUA levels affected gastric cancer risk. Using the fixed-effects IVW approach, our analysis revealed no significant association between SUA levels and gastric cancer risk, with P-values exceeding the threshold of significance in both populations (European P = 0.778; East Asian P = 0.245). The findings were supported by three additional MR methods. The reliability of these results was substantiated by comprehensive sensitivity analyses. In summary, our data do not support a significant causal linkage between SUA levels and gastric cancer risk.

Uric acid closely relates to both kidney disease and atrial fibrillation (AF), yet the extent to which it influences the kidney-AF association remains uncertain. We examined the relationship between kidney function and risk of AF, accounting for uric acid levels.

A total of 308,509 individuals in the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) cohort were included and their serum creatinine and uric acid were measured during 1985-1996. Ten-year incident AF was identified via linkage with the national registers. Glomerular filtration rate (eGFR) (ml/min/1.73 m2) was calculated with the 2009 Chronic Kidney Disease Epidemiology Collaboration equation. Hyperuricemia was defined as > 420 µmol/L for men and > 360 µmol/L for women.

Over a mean follow-up of 9.4 years, 10,007 (3.2%) incident AF cases occurred. After adjusting for age, sex, cardiovascular diseases, total cholesterol, triglycerides, and glucose, individuals with low eGFR (< 30 and 30-59 ml/min/1.73 m2 ) had a higher risk of AF compared to those with normal eGFR (60-89) (hazard ratio (HR) = 1.72, 95% confidence interval (CI):1.29-2.30; HR = 1.10, 95% CI: 1.03-1.18, respectively). After further adjusting for uric acid levels, the association disappeared (HR = 0.97, 95% CI: 0.72-1.30; HR = 0.93, 95% CI: 0.86-1.00, respectively). When stratifying by hyperuricemia yes/no, eGFR < 30 ml/min/1.73 m2 was associated with higher AF risk in a small group of individuals without hyperuricemia (HR = 2.58, 95% CI: 1.64-4.07).

Uric acid largely accounted for the relationship between eGFR and AF in this study. However, in individuals without hyperuricemia, eGFR in the lowest range (< 30 ml/min/1.73 m2) was still associated with increased risk of AF.

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.

Hyperuricemia is a relatively common condition, with a prevalence of over 20% among the general population. Also, most patients initially present no symptoms. This study aimed to investigate the knowledge, attitude, and practice (KAP) toward hyperuricemia among healthcare workers in Shandong, China.

Healthcare workers were recruited in this cross-sectional study conducted in Shandong in December 2022. A self-designed questionnaire was used to collect demographic information and KAP data.

A total of 372 questionnaires were distributed, and 216 (58.06%) valid questionnaires were collected from 131 physicians, 80 nurses, and five other healthcare workers. The participants had a mean score of 10.76 ± 2.53 (possible range: 0-14, 76.9%) and 31.94 ± 2.58 (possible range: 0-40, 79.9%) in knowledge and attitude, respectively. The physicians' and nurses' practice scores were 47.57 ± 5.34 (possible range: 0-55, 86.5%) and 30.06 ± 4.11 (possible range: 0-35, 85.9%), respectively. The attitude scores were independently associated with proactive practice in both physicians (P < 0.001) and nurses (P = 0.046).

This study found that healthcare workers in Shandong had adequate knowledge, positive attitudes, and proactive practices towards hyperuricemia. However, there is room for improvement in the attitudes of both physicians and nurses to achieve better practice.

Although the prevalence of thyroid dysfunction and hyperuricemia are independently high in patients with chronic kidney disease (CKD), there are limited data showing the association of serum uric acid and thyroid function in those with CKD.

The aim of this study was to observe the alteration of both the serum uric acid level and thyroid function in CKD patients and to find the association between both.

This observational cross-sectional study was conducted in a tertiary care hospital over a period of one year in Northeast India. A total of 50 CKD patients were enrolled. Their demographic profiles were studied. Serum urea, creatinine, thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), free triiodothyronine (FT3), total tetraiodothyronine (TT4), and free tetraiodothyronine (FT4) levels were measured to establish the correlation of serum uric acid along with each of the parameters separately. A p-value of <0.05 was considered statistically significant.

In the CKD patients studied, serum uric acid exhibited positive correlations with serum creatinine (p = 0.001, r = 0.67), serum urea (p = 0.001, r = 0.69), and serum TSH levels (p = 0.001, r = 0.5). Conversely, serum uric acid showed negative correlations with serum TT4 (p = 0.001, r = -0.74), TT3 (p = 0.001, r = -0.6), FT4 (p = 0.001, r = -0.53), and FT3 (p = 0.001, r = -0.58) levels.

 There was a significant positive correlation between uric acid and TSH levels in CKD patients. Thus, early estimation of both parameters should be considered in CKD patients.

The aim of the study was to explore the causes and clinical significance of hyperechoic renal medulla observed by ultrasonography in patients with primary gout.

This study included 2,107 patients with primary gout treated in the Gout Clinic of our hospital from 2016 to 2022. The clinical data and biochemical data of these patients were collected and analyzed. According to the presence or absence of punctate hyperechogenicity in the renal medulla on ultrasound examination, the patients were divided into the hyperechoic medulla (HM) and the normal hypoechoic medulla (NM) groups, and the HM group was further divided into the partial HM (P-HM) and fulfilled HM (F-HM) subgroups according to the distribution range of hyperechogenicity.

Among the 2,107 patients with primary gout, 380 had hyperechoic renal medulla on renal ultrasound, including 106 patients with F-HM and 274 with P-HM. There were significant differences in the gout duration, urate arthropathy number, serum urate (SU) level, clinical tophi number, blood urea nitrogen, serum creatinine (sCr), and estimated glomerular filtration rate between the HM and NM groups or between the F-HM and P-HM subgroups (p < 0.05). Multivariate regression analysis showed that the presence of HM was positively correlated with gout duration, urate arthropathy number, gout attack frequency, SU, and sCr. The number of clinical tophi and sCr were closely related to F-HM.

Ultrasound examination showed that a high medulla echo in patients with gout was often related to renal function damage. P-HM may be a transitory condition between NM and F-HM in patients with gout.

Hyperuricemic nephropathy (HN) is a global metabolic disorder characterized by uric acid (UA) metabolism dysfunction, resulting in hyperuricemia (HUA) and tubulointerstitial fibrosis (TIF). Sodium-dependent glucose transporter 2 inhibitor, dapagliflozin, has shown potential in reducing serum UA levels in patients with chronic kidney disease (CKD), though its protective effects against HN remain uncertain. This study investigates the functional, pathological, and molecular changes in HN through histological, biochemical, and transcriptomic analyses in patients, HN mice, and UA-stimulated HK-2 cells. Findings indicate UA-induced tubular dysfunction and fibrotic activation, which dapagliflozin significantly mitigates. Transcriptomic analysis identifies estrogen-related receptor α (ERRα), a downregulated transcription factor in HN. ERRα knockin mice and ERRα-overexpressed HK-2 cells demonstrate UA resistance, while ERRα inhibition exacerbates UA effects. Dapagliflozin targets ERRα, activating the ERRα-organic anion transporter 1 (OAT1) axis to enhance UA excretion and reduce TIF. Furthermore, dapagliflozin ameliorates renal fibrosis in non-HN CKD models, underscoring the therapeutic significance of the ERRα-OAT1 axis in HN and CKD.

A realistic exposure to ionizing radiation (IR) from an improvised nuclear device will likely include individuals who are partially shielded from the initial blast delivered at a very high dose rate (VHDR). As different tissues have varying levels of radiosensitivity, e.g., hematopoietic vs gastrointestinal tissues, the effects of shielding on radiation biomarkers need to be addressed. Here, we explore how biofluid (urine and serum) metabolite signatures from male and female C57BL/6 mice exposed to VHDR (5-10 Gy/s) total body irradiation (TBI, 0, 4, and 8 Gy) compare to individuals exposed to partial body irradiation (PBI) (lower body irradiated [LBI] or upper body irradiated [UBI] at an 8 Gy dose) using a data-independent acquisition untargeted metabolomics approach. Although sex differences were observed in the spatial groupings of urine signatures from TBI and PBI mice, a metabolite signature (N6,N6,N6-trimethyllysine, carnitine, propionylcarnitine, hexosamine-valine-isoleucine, taurine, and creatine) previously developed from variable dose rate experiments was able to identify individuals with high sensitivity and specificity, irrespective of radiation shielding. A panel of serum metabolites composed from previous untargeted studies on nonhuman primates had excellent performance for separating irradiated cohorts; however, a multiomic approach to complement the metabolome could increase dose estimation confidence intervals. Overall, these results support the inclusion of small-molecule markers in biodosimetry assays without substantial interference from the upper or lower body shielding.

The bidirectional effect of hyperuricemia on chronic kidney disease (CKD) underscores the importance of hyperuricemia as a risk factor for CKD. We evaluated the effect of hyperuricemia on the presence and development of CKD after considering genetic background by calculating polygenic risk scores (PRSs). We employed genome-wide association study summary statistics-excluding the United Kingdom Biobank (UKB) datasets among published CKD Gen Consortium papers-to calculate the PRSs for CKD in white background subjects. To validate PRS performance, we divided the UKB into two datasets to validate and test the data. We used logistic regression analysis to evaluate the association between hyperuricemia and CKD, and performed Kaplan-Meier survival analysis exclusively for subjects with available follow-up data. In total, 438,253 clinical data and 4,307,940 single nucleotide polymorphisms from 459,155 samples were included. We observed a significant positive association between PRS and CKD and the presence and development of CKD. Hyperuricemia significantly increased CKD risk (adjusted odds ratio 1.55, 95% confidence interval 1.48-1.61). The impact of hyperuricemia on CKD was maintained irrespective of PRS range. In addition, negative interaction between hyperuricemia and PRS for CKD was found. Survival analysis indicates that the presence of hyperuricemia significantly increased the risk of CKD development. The PRS for CKD thoroughly reflects the risk of CKD development. Hyperuricemia is a significant indicator of CKD risk, even after incorporating the genetic risk score for CKD. Irrespective of genetic risk, patients with a prospective risk of developing CKD require uric acid monitoring and management.

Trans fatty acids are specific unsaturated fats found in processed foods that undergo hydrogenation, leading to hepatic disorders such as metabolic-associated fatty liver disease (MAFLD) and conditions like CVD and CKD. The effects of different food samples containing trans fatty acids (elaidic and oleic acid) on the liver, heart, and kidney through antioxidant enzyme activity were investigated in animal models. Liver function tests (ALT, ALP, AST, and LDH), heart biomarker levels (CPK, TC, HDL, LDL, and triglycerides), and kidney biomarker levels (serum creatinine, blood urea nitrogen, and serum uric acid) were examined in serum of rabbits and the histopathology of liver tissues. Results showed that these biomarkers were more elevated in the Mujahid Ghee group than in the normal control, oleic acid, and Kausar Ghee groups. The concentration of antioxidant markers such as peroxidase, glutathione, catalase, thiobarbituric acid reactive substances, and superoxide dismutase were lower in the Mujahid Ghee group. HPLC showed that Mujahid Ghee had the highest quantified value of elaidic acid among all selected samples. Overall, this study demonstrated that elaidic acid in its purest form aggravated MAFLD in rabbit livers and provoked CVK and CVD.

Hyperuricemia is frequently observed in patients with type 2 diabetes (T2D) and is associated with increased risk of gout and cardiovascular disease (CVD). Empagliflozin lowers serum urate levels by enhancing its urinary excretion.

To compare initiators of empagliflozin vs dipeptidyl peptidase-4 inhibitor (DPP4i) and initiators of empagliflozin vs glucagon-like peptide-1 receptor agonist (GLP-1RA) with respect to the risk of incident gout events.

Using three claims-based datasets from 08/2014 to 09/2019, we generated two cohorts (cohort 1: empagliflozin vs DPP4i; cohort 2: empagliflozin vs GLP-1RA) of adult patients with T2D and without prior history of gout or gout-specific medication dispensing separately in each dataset. To assess the risk of incident gout, we estimated hazard ratios (HR) and rate differences (RD) per 1000 person-years (PY) with their 95% confidence intervals (CI) before and after 1:1 propensity score (PS) matching adjusting for 141 baseline covariates.

We identified 102,262 pairs of 1:1 propensity score-matched adults in cohort 1 and 131,216 pairs in cohort 2. Over a mean follow-up period of 8 months on treatment, the risk of gout was lower in patients initiating empagliflozin compared to DPP4i (HR = 0.69: 95% CI (0.60-0.79); RD =  - 2.27: 95% CI (- 3.08, 1.46)) or GLP-1RA (HR = 0.83: 95% CI (0.73-0.94); RD =  - 0.99: 95% CI (- 1.66, - 0.32)). Results were consistent across subgroups (sex, age, body mass index, chronic kidney disease, heart failure, cardiovascular disease, and concurrent diuretic use) and sensitivity analyses.

Among adults with T2D, the initiation of empagliflozin vs a DPP4i or GLP-1RA was associated with lower risk of incident gout, complementing results from a post hoc analysis of the EMPA-REG OUTCOME trial and previously published observational research focusing on the sodium-glucose co-transporter-2 inhibitor class in more narrowly defined study populations.

Hyperuricemia, characterized by elevated uric acid levels and subsequent crystal deposition, contributing to conditions such as gout, cardiovascular events, and kidney injury, poses a significant health threat, particularly in developed countries. Current drug options for treatment are limited, with safety concerns, leading to suboptimal therapeutic outcomes in symptomatic hyperuricemia patients and a lack of pharmaceutical interventions for asymptomatic cases. Distinguishing from the previous drug design strategies, we directly target uric acid, the pathological molecule of hyperuricemia, resulting in a pyrimidine derivative capable of increasing the solubility and excretion of uric acid by forming a complex with it. Its prodrug showed an anti-hyperuricemia activity comparable to benzbromarone and a favorable safety profile in vivo. Our finding provides a strategy purely based on organic chemistry to address the largely unmet therapeutic needs on novel anti-hyperuricemia drugs.