Hyperuricemia Research Articles

Hyperuricemia (HUA) impairs sperm function via oxidative stress and metabolic dysregulation. This retrospective cohort study aimed to investigate the therapeutic effect of density gradient centrifugation (DGC) on HUA-associated sperm dysfunction. A total of 490 couples undergoing their first intrauterine insemination (IUI) were stratified into the HUA group (200 cycles) and control group (290 cycles) based on male serum uric acid levels. At baseline, the percentage of progressively motile sperm (PR%) in the HUA group was significantly lower than that in the control group (39.55% ± 11.29% vs. 41.76% ± 11.89%, P = 0.040). Following DGC processing, PR% in both groups exceeded 90% with no significant intergroup difference; however, the increase in PR% (ΔPR%) was significantly greater in the HUA group (52.34% ± 10.62% vs. 50.29% ± 11.02%, P = 0.040). No significant difference was observed in the clinical pregnancy rate between the two groups (11.0% vs. 13.4%, P = 0.230). DGC specifically improves sperm motility in patients with HUA. While direct measurement of mechanistic markers (e.g., oxidative stress, metabolic factors) was not performed in this study, this motility-improving effect may correlate with DGC's known capacity to scavenge reactive oxygen species and optimize energy supply-an inference supported by prior mechanistic studies. However, improving sperm motility alone is insufficient to significantly enhance clinical pregnancy rates. These findings provide insights to optimize semen preparation strategies in HUA-associated male infertility.

Hyperuricemia (HUA) is the second most common metabolic disease after diabetes and refers to a type of disease in which serum uric acid (SUA) levels are excessively high due to excessive production of uric acid (UA) or reduced metabolic capacity. To elucidate the effect of HUA on angiogenesis in endometrial decidualization, the authors investigated endometrial decidualization markers and angiogenesis factors in the decidua after abortion in women with high uric acid levels and the uterus of mice with high uric acid induced by purines on day 7.5 (D7.5) of gestation. Moreover, immunohistochemical staining was used to measure the diameter of the microvascular lumen and the density of the vessels. Real-time PCR and Western blot results showed that the expressions of prolactin (PRL) and decidua/trophoblast PRL-related protein prolactin family 8, subfamily a, member 2 (Prl8a2) in the decidua of patients with hyperuricemia and the pregnant uterus of high uric acid mice with D7.5 days of gestation were significantly reduced. Additionally, the diameter and density of the microvascular lumen were decreased by immunohistochemical staining of uterine CD34. The expression of vascular endothelial growth factor a (VEGFA) in the endometrium was significantly decreased (P < 0.05). High UA can lead to endometrial decidualization damage and angiogenesis disorders in early pregnancy in humans and mice.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-22489-y.

BackgroundSerum uric acid(SUA) is proinflammatory and increases the risk of cardiovascular events in patients with coronary artery disease. SUA levels differ between men and women, and it is unclear whether there are gender differences in the correlation between SUA levels and major adverse cardiovascular events (MACE) in patients with acute coronary syndromes (ACS). In this paper, we analyze the correlation between SUA and MACE in men and women with ACS respectively, to achieve a more accurate prognosis prediction and to determine the optimal level of SUA control in ACS patients of different genders.MethodsThis was a retrospective cohort study that ultimately selected 2799 ACS patients who were hospitalized in the Department of Cardiology of the Affiliated Hospital of Jining Medical College from May 2013 to October 2015, and grouped the patients according to the gender-specific criteria for hyperuricemia(HUA). With a mean follow-up of 4.42 years after discharge, MACE were collected, and the correlation between SUA and MACE risk in patients of different genders was investigated using the Cox proportional risk regression model. Smooth curve fitting was used to analyze the nonlinear relationship between SUA and MACE, and sensitivity and subgroup analyses were performed to investigate further the correlation between SUA and MACE in different populations.ResultsA total of 309 patients developed MACE during the follow-up period. Kaplan-Meier curves showed that patients with HUA had a higher risk of MACE (p < 0.01). Multivariate Cox proportional risk regression modeling analysis revealed a significant correlation between SUA and MACE risk. In crude Cox analyses, SUA levels were associated with higher risk of MACE (total: HR 1.22,95% CI 1.13, 1.31, p < 0.0001, men: HR 1.24, 95% CI 1.14, 1.35, p < 0.0001, women: HR 1.16, 95% CI 1.00, 1.34, p = 0.0477). However, after adjusting for various covariates including SYNTAX scores(SS), the prediction of MACE risk by SUA was clinically significant only in men (HR 1.21, 95% CI 1.03, 1.42, p = 0.0191), and the incidence of MACE events was elevated with elevated uric acid in women but was not clinically significant (HR 1.06, 95% CI 0.82, 1.38, p = 0.6633). In addition, when results were analyzed according to SUA tertiles and gender, men with higher SUA tertiles had a higher risk of MACE (p < 0.0001). After adjusting for variables, smoothed-fit curve analysis similarly showed a trend toward higher MACE occurrence with elevated uric acid in a variety of populations. The inflection points present in the threshold effect analysis in the whole population, men and women curve fits were 7.11 mg/dL, 7.13 mg/dL, and 6.31 mg/dL, respectively, and for every 1-unit increase in uric acid to the right of the inflection point, the risk of MACE increased by 1.48-fold, 1.24-fold, and 1.48-fold, respectively. (( HR (95%) CI: 2.48 (1.57, 3.90) p < 0.0001, in total; 2.24 (1.37, 3.65) p = 0.0013, in men; 2.48 (1.02, 6.01) p = 0.0442, in women)). Subgroup analyses and interaction tests showed that the association between uric acid and MACE was more significant in men in the high triglyceride and high LDL population, whereas in women it was more significant in patients with high BMI, mild coronary artery stenosis, high creatinine, and normoglycemia (interaction p-value < 0.05).ConclusionsThere is a gender difference in the risk of MACE and uric acid levels in patients with ACS, with elevated uric acid levels being more likely to lead to cardiovascular events in men patients, whereas there was no significant difference in women patients.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12872-025-05262-x.

Gut dysbiosis contributes to hyperuricemia (HUA), yet plant-based synbiotics that boost short-chain fatty acids (SCFAs) are underexplored. We developed a kiwifruit-derived synbiotic combining Lactiplantibacillus plantarum LP220 with kiwifruit powder and evaluated its effects in vitro and in an adenine and potassium oxonate mouse HUA model (8 weeks). In vitro, LP220 produced propionate 2.528 ± 0.369 μg/109 CFU/mL and butyrate 36.06 ± 2.353 μg/109 CFU/mL. In vivo, the synbiotic lowered serum uric acid by 62.27% versus untreated HUA (P < 0.01) and outperformed LP220 or kiwifruit alone, increasing fecal/serum and urinary/serum uric acid ratios by 242.99 and 117.49% (P < 0.01). Fecal and serum propionate and butyrate rose 38.01-129.34% (P < 0.01), accompanied by reduced systemic inflammation (serum LPS - 38.81%; IL-1β - 23.74%). Mechanistically, the synbiotic decreased hepatic xanthine oxidase activity and upregulated ABCG2 expression in colon and kidney, with recovery of gut diversity and enrichment of SCFAs-producers. These results indicate the kiwifruit synbiotic suppresses urate synthesis and promotes excretion via SCFA-mediated microbiota-host interactions, suggesting a microbiota-targeted nutritional strategy for HUA.

Isobavachin alleviates hyperuricemia-induced bone loss by GPR35-NLRP3 signal.

Revisiting the metabolic crosstalk between type 2 diabetes and hyperuricemia: Pathophysiological insights and therapeutic perspectives.

Moderate-intensity exercise attenuates bone loss in hyperuricemic nephropathic mice.

The interplay of NAD+, hyperuricemia, and renal damage: A scientific review.

Novel FAD-dependent uricase produced by food-sourced Priestia megaterium and activity assessment using hyperuricemia Caenorhabditis elegans.

MicroRNA-93-5p alleviates uric acid-induced fibrosis in renal tubular epithelial cells by regulating the SMAD5/Id2 signaling pathway.

Although laparoscopic sleeve gastrectomy (LSG) effectively addresses obesity, its outcomes on hyperuricemia (HUA) remission remain inconsistent. We aimed to identify baseline predictors and develop a nomogram for HUA persistence six months following LSG. We retrospectively analyzed patients with obesity and HUA undergoing primary LSG at Huashan Hospital. An independent validation cohort from the Affiliated Hospital of Xuzhou Medical University was included. Clinical data, including demographics, anthropometric measurements, and biochemical markers were analyzed. Logistic regression analyses identified independent predictors of persistent HUA, and a predictive nomogram was developed and externally validated. A total of 631 patients was enrolled in this study. Persistent HUA was observed in 41.8% (159/380) of patients in the training cohort. Multivariate analysis identified male sex (OR = 4.97, 95% CI: 2.35-10.51, P < 0.001), waist circumference (WC; OR = 1.06, 95% CI: 1.02-1.10, P = 0.006), and baseline UA levels (OR = 1.01, 95% CI: 1.01-1.02, P < 0.001) as significant predictors. The nomogram demonstrated excellent discriminative ability (AUC = 0.85, 95% CI: 0.82-0.86) and calibration. In the validation cohort, persistent HUA was observed in 35.5% (89/251), and the nomogram maintained robust predictive performance (AUC = 0.81, 95% CI: 0.76-0.82). Male sex, increased WC, and elevated baseline UA predict postoperative persistent HUA. The nomogram provides a practical clinical tool for predicting short-term HUA non-remission post-LSG.

Background: Hyperuricemia (HUA), a metabolic disorder characterized by high serum uric acid (UA) level, presents a growing global health challenge. Method: In this study, a stable murine model of HUA was established by orally administering adenine (100 mg/kg) and potassium oxonate (600 mg/kg) in C57BL/6J mice, resulting in significant elevation of serum UA and xanthine oxidase (XOD) activity, as well as renal pathological alterations. Given the anti-hyperuricemia potential of Lactiplantibacillus plantarum WLPL04, a strain from a human breast milk was evaluated. Conclusions: Oral administration of L. plantarum WLPL04 significantly reduced serum UA level and XOD activity in a dose-dependent manner. Moreover, L. plantarum WLPL04 treatment enhanced UA excretion by upregulating ABCG2 and downregulating URAT1 and GLUT9 expression. It ameliorated renal injury and suppressed inflammation via downregulation of the NLRP3 inflammasome pathway. 16S rRNA gene sequencing revealed that L. plantarum WLPL04 restored gut microbial diversity and promoted the enrichment of beneficial genera such as Bacteroides, which was negatively correlated with UA in serum, creatinine, and inflammatory cytokines. Moreover, transcript analysis revealed upregulation of purine salvage genes (hpt and xpt), suggesting enhanced salvage pathway recycling of purine bases and reduced urate production. Those findings suggest that L. plantarum WLPL04 exerted multi-targeted anti-hyperuricemia effects through coordinated regulation of host purine metabolism, urate transport, inflammation, and gut microbiota composition, providing a promising probiotic candidate for HUA management.

Hyperuricemia (HUA), a metabolic disorder characterized by elevated serum uric acid resulting from imbalanced production and excretion, is associated with gout and other serious health issues. This study aimed to screen out the potential probiotics with HUA-alleviating properties among 20 Lactobacillus strains. The results showed that L. reuteri Urob-7 exhibited the highest degradation rates for inosine and guanosine (82.10% and 88.78%, respectively) and strong xanthine oxidase (XOD) inhibitory activity (62.86%). In a HUA mouse model induced by inosine, guanosine, and potassium oxonate, L. reuteri Urob-7 intervention significantly reduced serum uric acid levels by 46.54%, restoring them to levels similar to control groups, and improved kidney function indicators. Moreover, Urob-7 reduced hepatic XOD activity by 37.6% and downregulated XOD expression in the intestines, decreasing excessive uric acid synthesis. It also significantly inhibited the NF-κB/NLRP3 inflammatory pathway, reducing the expression levels of NF-κB and NLRP3 in the kidneys by 39.3% and 47.6%, respectively. Furthermore, L. reuteri Urob-7 increased the abundance of short-chain fatty acid-producing bacteria (e.g., Ruminococcus and Intestinimonas) while reducing the proportion of pathogenic bacteria (e.g., Bacteroides and Anaerovorax), thus ameliorating gut microbiota dysbiosis and intestinal barrier dysfunction. In summary, L. reuteri Urob-7 effectively relieved HUA by modulating uric acid metabolism, suppressing inflammation, and improving gut microbiota balance. These results highlighted its potential as a promising candidate for HUA.

Hyperuricemia exacerbates acetaminophen hepatotoxicity via JNK activation and mitophagy reduction.

Background Diabetic kidney disease (DKD) combined with hyperuricemia (HUA) constitutes a pathological state of vicious cycle, where diabetic microvascular complications affect the kidneys and interact with persistent hyperuricemia. This condition significantly accelerates the progression of renal failure and increases all-cause mortality. Objective This study aims to systematically evaluate the clinical efficacy and safety of febuxostat in treating patients with DKD and HUA via a meta-analysis, thereby providing evidence-based guidance for optimizing clinical medication. Methods Following the PICOS principle, we systematically searched for randomized controlled trials (RCTs) on febuxostat for treating DKD combined with HUA, covering the period from the establishment of each database to June 26, 2025. Studies meeting the inclusion criteria were selected, and a meta-analysis was performed using Review Manager 5.4 software. Results A total of 17 RCTs were included, involving 1,300 patients (treatment group n=647, control group n = 653). The results of the meta-analysis showed that the overall effective rate of the febuxostat treatment group was significantly higher than that of the control group (RR = 1.24, 95%CI: 1.17–1.32; Z = 7.17, P &amp;lt; 0.001). In addition, febuxostat significantly reduced serum uric acid (SUA), urinary albumin-to-creatinine ratio (UACR), serum creatinine (Scr), and blood urea nitrogen (BUN) levels, and improved the estimated glomerular filtration rate (eGFR) ( P &amp;lt; 0.001 for all indicators). Conclusion This meta-analysis indicates that febuxostat, when used to treat patients with DKD and HUA, can significantly enhance overall clinical effectiveness and effectively improve key renal function indicators—including SUA, UACR, Scr, BUN, and eGFR. The results of this study showed that when febuxostat is used to treat patients with diabetic nephropathy complicated by hyperuricemia, it achieves a higher overall clinical response rate. It can significantly reduce the levels of SUA, UACR, Scr, and BUN in patients, while improving the eGFR. Additionally, the incidence of adverse reactions associated with febuxostat is lower, suggesting that this drug exhibits favorable clinical safety. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/ .

Abstract Background and Aims Previous studies from our group have highlighted anti-inflammatory and anti-oxidative properties of asymptomatic hyperuricemia (HU) in kidney disease and sterile inflammation, suggesting a compensatory physiological mechanism of autoregulation. Notably, diabetes mellitus (DM) is common in patients with CKD, where hyperglycemia-related glomerular hyperfiltration exacerbates nephron hypertrophy, thereby promoting proteinuria and nephron loss. However, the role of HU as a vasoconstrictor in the context of CKD plus DM remains poorly understood. We hypothesized that HU exhibits vasoactive effects in mice with CKD and that the presence of DM may mitigate crystalluria-associated CKD. Method To do so, we used our innovative animal models of HU with uric acid crystal-induced CKD (HU plus CU-CKD) and HU with aristolochic acid-induced CKD (HU plus AA-CKD, non-crystalline). Additionally DM was induced by injecting streptozotocin in Alb-creERT2; Glut9lox/lox mice and Glut9lox/lox (healthy) control mice. On day 28, 42 and 56, the GFR was determined, and blood and urine collected for measuring creatinine and BUN levels and urinary pH. On day 56, mice were sacrificed and kidneys harvested for immunohistochemistry staining (PAS, Picro Sirius red, F4/80, WT-1, αSMA/fibrin, Ly6G) and RT-qPCR (KIM-1, TNFα, TGF-β, Fibronectin). FACS analysis was performed to quantify the numbers of neutrophils and monocytes in blood. Results We found that the GFR significantly dropped in HU plus CU-CKD mice compared to the healthy and DM groups (Fig. 1A). Interestingly, HU plus CU-CKD mice with concomitant DM were protected from kidney disease, as demonstrated by a normal GFR and less tubular injury, inflammation and interstitial fibrosis. Mechanically, DM reduced the formation of renal uric acid crystals, promoted hyperfiltration, and increased the urinary pH in HU plus CU-CKD mice. This strong protective effect of DM in crystalluria-related CKD was not observed in HU plus AA-CKD mice (non-crystalline model). In these mice, concomitant DM did not improve kidney function nor prevented kidney injury. Additionally, in both the HU plus CU-CKD and HU plus AA-CKD models, DM contributed to renal vasodilation, while HU induced vasoconstriction (Fig. 1B). Conclusion Our results show that HU has vasoactive effects in mice with CKD and that DM exhibits renoprotective properties by preventing uric acid crystal deposition and therefore kidney injury, inflammation and fibrosis. This might be an explanation for the lower risk of kidney stones in CKD patients with DM.

The relationship between the calcium-phosphorus product (Ca × P) and hyperuricemia (HUA) has not been thoroughly explored. This study sought to investigate this association across BMI groups in US adults. A cross-sectional analysis was conducted using the 2017-2018 National Health and Nutrition Examination Survey (NHANES) dataset (N = 5068). The association was evaluated through restricted cubic splines, logistic regression, and mediation analysis. Participants in the highest quartile of Ca × P had a 1.31-fold higher odds of HUA (OR 1.31; 95% CI 1.04-1.65) compared to those in the lowest quartile. A positive linear association between Ca × P and HUA was observed among overweight or obese individuals (OR 1.04; 95% CI 1.01-1.08 and OR 1.04; 95% CI 1.01-1.06, respectively). In the obese subgroup, those in the highest Ca × P quartile had a 1.50-fold increased odds of HUA (OR 1.50; 95% CI 1.11-2.03). Moreover, serum triglycerides mediated 23.12% of the association between Ca × P and HUA in obese adults, showing differential effect patterns. Ca × P levels were positively associated with a greater prevalence of HUA, especially in the overweight or obesity population. Serum triglycerides play a crucial mediating role in the relationship between Ca × P and HUA among obese people. Key Points • Elevated per Ca × P level is significantly associated with a 3% increased risk of hyperuricemia among US adults, with individuals in the highest quartile exhibiting 1.31-fold higher odds compared to those in the lowest quartile. • The association between Ca × P and hyperuricemia is notably stronger in overweight and obese populations, with obese adults in the highest Ca × P quartile showing a 1.5-fold increased risk of hyperuricemia. • Serum triglycerides mediate 23.12% of the relationship between Ca × P and hyperuricemia in obese individuals, indicating a substantial metabolic pathway influencing hyperuricemia development in this high-risk group.

Abstract Background and Aims Globally, the prevalence of hyperuricemia (HUA) has exceeded 20% and is shifting toward younger age groups. Chronic kidney disease (CKD) is a common complication of gout, with approximately 24% of gout patients progressing to stage Ⅲ or higher CKD. However, the dose-response relationship between serum uric acid (SUA) levels and CKD development in gout patients remains unexplored. This study, focusing on gout patients in Southwest China, aimed to investigate the relationship and dose-response relationship between SUA levels and CKD risk, providing a scientific basis for CKD prevention and management. Method We collected clinical data from 502 gout patients who visited our hospital between February 2023 and February 2024. Gout diagnosis was based on the criteria established by the 2015 American College of Rheumatology (ACR) guidelines. The estimated glomerular filtration rate (eGFR) was calculated based on creatinine levels using the CKD Epidemiology Collaboration 2021 (CKD-EPI) equation, with CKD defined as eGFR &amp;lt;60 ml/min/1.73 m². Patients were divided into two groups based on eGFR: the CKD group (eGFR &amp;lt; 60 ml/min/1.73 m²) and the non-CKD group (eGFR ≥ 60 ml/min/1.73 m²). Multivariate logistic regression was used to assess the association with CKD. A three-node restricted cubic spline (RCS) was employed to model the dose-response relationship between SUA levels and the development of CKD, based on model 2. P-values &amp;lt; 0.05 were considered statistically significant. Results The mean SUA was higher in CKD patients (629.15 μmol/l) compared to non-CKD patients (581.2 μmol/l), (P = 0.006) (Table 1). No significant association was found between CKD and gouty arthritis (χ = 2.332, P = 0.267). However, the presence of CKD was significantly linked to the development of gouty stones (χ = 6.028, P = 0.022). Additionally, three models were developed to adjust for confounders and further examine the relationship between SUA and CKD (Table 2). The results indicated a strong positive correlation between SUA and CKD. In the unadjusted model, the odds ratio (OR) was 1.002, with a 95% confidence interval (CI) of 1.000 to 1.004 (P = 0.023). This positive association remained statistically significant after adjusting for all confounders in Model 3 (P = 0.034). Using Model 2, the dose-response relationship between CKD and HUA was further explored through RCS analysis. The continuous change in SUA was plotted on the horizontal axis, while the risk of CKD occurrence was plotted on the vertical axis. The results revealed a significant association between SUA levels and CKD incidence risk (P = 0.035). However, the non-linear relationship was not significant, suggesting a more linear association. This implies that the risk of CKD may exhibit a regular upward or downward trend as SUA levels change, rather than a complex curvilinear relationship (Fig. 1). Conclusion In gout patients, serum uric acid (SUA) is a significant risk factor for the development of CKD, with the risk of CKD exhibiting a consistent upward or downward trend as SUA levels change. This study offers valuable scientific evidence for the prevention and management of CKD in gout patients, emphasizing that close monitoring of SUA levels and timely intervention could reduce CKD risk and improve clinical outcomes.

BackgroundThere have been sufficient previous studies demonstrating that hyperuricemia (HUA) is closely associated with the occurrence of atrial fibrillation (AF).The incidence of AF in patients with hyperuricemia is higher than that in the general population. Therefore, it is meaningful to explore the serum markers of AF in the HUA population and establish early warning indicators.ObjectiveTo preliminarily explore the correlation between HUA and AF at the metabolomics level, and to identify a group of metabolites with potential predictive power for AF that can be used for further large-scale studies.MethodsThis study used untargeted metabolomics technology to detect serum metabolites of patients with AF, patients with AFHUA, and control group. Receiver operator characteristic (ROC) curve were used to analyze differential metabolites.ResultsUltimately, multiple metabolites such as L-Threonine, DL-Malic acid, L-Valine, L-Cysteine were identified as early warning markers of AF in patients with HUA. Combined ROC curve using these four metabolites between the AFHUA/Control comparison group and the AFHUA/AF comparison group showed good predictive efficacy, with Area Under the ROC Curve (AUC) = 0.923 (P < 0.001) in the AFHUA/Control comparison group and AUC = 0.714 (P < 0.001) in the AFHUA/AF comparison group. This provides an early predictive method for patients who may develop atrial fibrillation among those with hyperuricemia. And offers new approaches for the prevention and treatment of atrial fibrillation.ConclusionThis study indicates that serum metabolomics can be specifically used to predict the probability of AF occurrence in individuals with HUA, and has identified metabolites such as L-Threonine, DL-Malic acid, L-Valine, and L-Cysteine that possess potential predictive efficacy.

The first part of this review analyzes the impact of red meat, meat products, meat by-products, and alternative protein sources, including artificial meat, on serum uric acid levels and the risk of developing gout. For decades, meat products rich in purines were considered among the main risk factors for hyperuricemia (HUA) and gout. However, recent studies suggest that the relationship between meat consumption and the development of gout is far less straightforward than previously thought. The authors attempt to address whether complete exclusion of these products is truly necessary, or whether a balance between diet and control of HUA can be achieved.