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Objective: Hyperuricemia can be stratified into four subtypes according to renal uric acid handling. The aim of this study was to comprehensively describe the biologic characteristics (including genetic background) of clinically defined hyperuricemia subtypes in two large geographically independent gout cohorts., Methods: Hyperuricemia subtype was defined as renal uric acid overload (ROL), renal uric acid underexcretion (RUE), combined, or renal normal. Twenty single nucleotide polymorphisms (SNPs) previously identified as gout risk loci or associated with serum urate (SU) concentration in the East Asian population were genotyped. Weighted polygenic risk scores were calculated to assess the cumulative effect of genetic risks on the subtypes., Results: Of the 4,873 participants, 8.8% had an ROL subtype, 60.9% RUE subtype, 23.1% combined subtype, and 7.2% normal subtype. The ROL subtype was independently associated with older age at onset, lower SU, tophi, and diabetes mellitus; RUE was associated with lower body mass index (BMI) and non-diabetes mellitus; the combined subtype was associated with younger age at onset, higher BMI, SU, estimated glomerular filtration rate (eGFR), and smoking; and the normal subtype was independently associated with older age at onset, lower SU, and eGFR. Thirteen SNPs were associated with gout with 6 shared loci and subtype-dependent risk loci patterns. High polygenic risk scores were associated with ROL subtype (odds ratio [OR] = 9.63, 95% confidence interval [95% CI] 4.53-15.12), RUE subtype (OR = 2.18, 95% CI 1.57-3.03), and combined subtype (OR = 6.32, 95% CI 4.22-9.48) compared with low polygenic risk scores., Conclusion: Hyperuricemia subtypes classified according to renal uric acid handling have subtype-specific clinical and genetic features, suggesting subtype-unique pathophysiologic mechanisms., (© 2024 American College of Rheumatology.)

Objective: To investigate the incidence and potential risk factors for development of fenofibrate-associated nephrotoxicity in gout patients., Methods: A total of 983 gout patients on fenofibrate treatment who visited the dedicated Gout Clinic at the Affiliated Hospital of Qingdao University between September 2016 and June 2020 were retrospectively enrolled from the electronic records system. Fenofibrate-associated nephrotoxicity was defined as an increase in serum creatinine (SCr) ≥0.3 mg/dl within 6 months of fenofibrate initiation. The change trend of SCr and uric acid levels during the treatment period were assessed by a generalised additive mixed model (GAMM). Multivariate analysis was performed for risk factors affecting elevated SCr., Results: A total of 100 (10.2%) patients experienced an increase in SCr ≥0.3 mg/dl within 6 months after fenofibrate initiation. The median change of SCr in the whole cohort was 0.11 mg/dl [interquartile range (IQR) 0.03-0.20], whereas it was 0.36 (0.33-0.45) in the fenofibrate-associated nephrotoxicity group. In a multivariable regression model, chronic kidney disease (CKD) [odds ratio (OR) 2.39 (95% CI 1.48, 3.86)] and tophus [OR 2.29 (95% CI 1.39, 3.78)] were identified to be risk predictors, independent of measured covariates, of fenofibrate-associated nephrotoxicity. During the treatment period, although SCr temporarily increased, serum urate and triglyceride concentrations decreased using the interaction analysis of GAMM. Of those with fenofibrate withdrawal records, the SCr increase in 65% of patients was reversed after an average of 49 days off the drug., Conclusions: This observational study implied that fenofibrate-associated nephrotoxicity occurs frequently in gout patients, especially in patients with tophi or CKD. The potential renal risks of fenofibrate usage in gout needs additional research., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To clarify the relationship between serum urate (SU) decrease and visceral fat area (VFA) reduction in patients with gout., Methods: We retrospectively analyzed 237 male gout patients who had two sets of body composition and metabolic measurements within 6 months. Subjects included had all been treated with urate-lowering therapy (ULT) (febuxostat 20-80 mg/day or benzbromarone 25-50 mg/day, validated by the medical record). All patients were from the specialty gout clinic of The Affiliated Hospital of Qingdao University. The multiple linear regression model evaluated the relationship between change in SU [ΔSU, (baseline SU) - (final visit SU)] and change in VFA [ΔVFA, (baseline VFA) - (final visit VFA)]., Results: ULT resulted in a mean (standard deviation) decrease in SU level (464.22 ± 110.21 μmol/L at baseline, 360.93 ± 91.66 μmol/L at the final visit, p < 0.001) accompanied by a decrease in median (interquartile range) VFA [97.30 (81.15-118.55) at baseline, 90.90 (75.85-110.05) at the final visit, p < 0.001]. By multiple regression model, ΔSU was identified to be a significant determinant variable of decrease in VFA (beta, 0.302; p = 0.001)., Conclusions: The decrease in SU level is positively associated with reduced VFA. This finding provides a rationale for clinical trials to affirm whether ULT promotes loss of visceral fat in patients with gout., Competing Interests: RT is funded by a research award from Astra-Zeneca and has consulted with Horizon, Selecta, SOBI, and Astra-Zeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ran, Xue, Han, Terkeltaub, Merriman, Zhao, He, Wang, Li, Liu, Cui, Li, Ji, Hu, Lu and Li.)

Background: The prevalence of hyperuricemia is increasing in adults, while the prevalence among adolescents is seldom reported., Methods: A cross-sectional survey by multistage, stratified sampling method was carried out in Shandong Province during 2017-2018. A total of 9371 adolescents aged from 13 to 19 years were randomly sampled and analyzed in this survey., Results: The overall mean serum uric acid (sUA) concentration was 6.08 ± 1.57 mg/dL and overall hyperuricemia prevalence was 25.4% and 60.5% (when hyperuricemia was defined as sUA ≥ 7 mg/dL or ≥ 5.5 mg/dL). Prevalence were 42.3% (male) and 8.0% (female) when limit was 7 mg/dL and prevalence were 82.1% (male) and 38.4% (female) when limit was 5.5 mg/dL. Male gender, increased body mass index, increased waist circumstance, increased triglycerides, increased fasting blood glucose, increased systolic blood pressure, decreased estimated glomerular filtration rate, and positive family gout history were associated with the enhanced risk of hyperuricemia according to univariate and/or multivariate logistic regression analysis. Food intake frequency of carbonate beverage, mutton, and other kinds varied between hyperuricemia adolescents and normal sUA ones., Conclusions: The studied adolescent population showed sUA level and hyperuricemia prevalence which are even higher than those of adults in China. The epidemic of youth hyperuricemia may pose a future threat of gout attacks and other hyperuricemia-related diseases, which alarms the public, health professionals and health policy makers to prepare the future health challenges.

Background: Serum uric acid (SUA), hyperuricemia (HUA) and gout are complex traits with relatively high heritability. This study aims to identify whether a candidate gene, SLC28A2 , exerts susceptibility for SUA fluctuation and incidence of HUA and gout in the Han Chinese population., Results: Three sample sets of 1376 gout patients, 1290 long-term HUA subjects (no gout attack) and 1349 normouricemic controls were recruited for this study. Eight polymorphisms in the SLC28A2 gene were genotyped using the ligase detection reaction-polymerase chain reaction (LDR-PCR) technology. Rs16941238 showed the most significant associations with SUA level (minor allele "A", BETA = - 13.84 μmol/L, P  = 0.0041, P perm  = 0.0042) and HUA (OR = 0.7734, P  = 0.0033, P perm  = 0.0020), but not with gout (OR = 0.8801, P  = 0.1315, P perm  = 0.1491). Rs2271437 was significantly associated with gout (minor allele "G", OR = 1.387, P  = 0.0277, P perm  = 0.0288), and was further confirmed in the meta-analysis with the previously published gout GWAS dataset (OR = 1.3221, P  = 0.0089). Each variant basically conferred consistent OR direction on gout and HUA, compared with the normouricemic control., Conclusions: Our findings support the associations of the SLC28A2 gene with the SUA level, the HUA phenotype and gout in Han Chinese., Competing Interests: The study was approved by the Ethics Committee of Shanghai Jiao Tong University and the Affiliated Hospital of Qingdao University, and in accordance with the principles of the Declaration of Helsinki. All participants gave their written informed consent to take part in the present study.Not applicable.The authors declare no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The urate oxidase (Uox) gene encodes uricase that in the rodent liver degrades uric acid into allantoin, forming an obstacle for establishing stable mouse models of hyperuricemia. The loss of uricase in humans during primate evolution causes their vulnerability to hyperuricemia. Thus, we generated a Uox-knockout mouse model on a pure C57BL/6J background using the transcription activator-like effector nuclease (TALEN) technique. These Uox-knockout mice spontaneously developed hyperuricemia (over 420 μmol/l) with about 40% survival up to 62 weeks. Renal dysfunction (elevated serum creatinine and blood urea nitrogen) and glomerular/tubular lesions were observed in these Uox-knockout mice. Male Uox-knockout mice developed glycol-metabolic disorders associated with compromised insulin secretion and elevated vulnerability to streptozotocin-induced diabetes, whereas female mice developed hypertension accompanied by aberrant lipo-metabolism. Urate-lowering drugs reduced serum uric acid and improved hyperuricemia-induced disorders. Thus, uricase knockout provides a suitable mouse model to investigate hyperuricemia and associated disorders mimicking the human condition, suggesting that hyperuricemia has a causal role in the development of metabolic disorders and hypertension., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Gout is a chronic disease resulting from elevated serum urate (SU). Previous genome-wide association studies (GWAS) have identified dozens of susceptibility loci for SU/gout, but few have been conducted for Chinese descent. Here, we try to extensively investigate whether these loci contribute to gout risk in Han Chinese. A total of 2255 variants in linkage disequilibrium (LD) with GWAS identified SU/gout associated variants were analyzed in a Han Chinese cohort of 1255 gout patients and 1848 controls. Cumulative genetic risk score analysis was performed to assess the cumulative effect of multiple "risk" variants on gout incidence. 23 variants (41%) of LD pruned variants set (n = 56) showed nominal association with gout in our sample (p < 0.05). Some of the previously reported gout associated loci (except ALDH16A1), including ABCG2, SLC2A9, GCKR, ALDH2 and CNIH2, were replicated. Cumulative genetic risk score analyses showed that the risk of gout increased for individuals with the growing number (≥8) of the risk alleles on gout associated loci. Most of the gout associated loci identified in previous GWAS were confirmed in an independent Chinese cohort, and the SU associated loci also confer susceptibility to gout. These findings provide important information of the genetic association of gout.

Objective Gout flares during urate-lowering therapy (ULT) initiation are common, but predictors of these flares are poorly understood. The aim of this study was to determine whether serum CA72-4 is an independent predictor for gout flares during ULT initiation. Methods A prospective cohort study was conducted between March 2021 and January 2022. Men with gout, at least one gout flare in the past year, and at least three serum CA72-4 measurements in the previous six months were enrolled. Participants were grouped according to their highest recorded serum CA72-4 levels (above or within the normal range). All participants took oral febuxostat 20 mg daily without flare prophylaxis therapy, and attended face-to-face visits every four weeks until 24 weeks. The incidence of gout flare was compared between the two groups. Backward stepwise logistic regression analyses were used to identify risk factors associated with flares. Receiver operating characteristic curve analysis was used to evaluate prediction efficacy. Results A total of 193 completed the study (79 with high CA72-4; 114 with normal CA72-4). The cumulative incidence of at least one gout flare was 48.1% (62.1% in the high CA72-4 group, 38.4% in the normal CA72-4 group, P  = 0.001), and recurrent (≥2) flares was 33.0% (47.1% in the high CA72-4 group, 23.2% in the normal CA72-4, P  < 0.001). High CA72-4, disease duration, intra-articular tophus size, glucose, high-density lipoprotein-cholesterol and ESR were independent risk factors for gout flares. Serum CA72-4 alone predicted recurrent flares with an area under the curve of 0.63 (95% CI = 0.54, 0.71), and 0.78 (95% CI = 0.71, 0.85) when combined with other independent variables. Conclusion High serum CA72-4 predicts the risk of gout flares during ULT initiation. Trial registration ChiCTR; https://www.chictr.org.cn/ ; ChiCTR2100043573. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-17 is a proinflammatory cytokine mainly secreted by activated T helper 17 cells and involved in inflammatory immune responses. This study aimed to investigate the association between IL-17 variants as well as serum IL-17 levels with gout in male Chinese Han individuals. A total of 1,101 male gout patients and 1,239 ethic-matched controls were enrolled. Genetic distributions of three variants (rs2275913 in IL-17A, rs763780 in IL-17F, and rs4819554 in IL-17RA) were detected by real-time polymerase chain reaction using the Taqman probe method. The plasma concentrations of IL-17A and IL-17F were measured in 228 gout patients and 198 controls that came from above samples by an enzyme-linked immunosorbent assay. No significant differences were observed in the genetic distribution of these polymorphisms between cases and controls (rs2275913: χ2 = 0.15, p = 0.928 by genotype, χ2 = 0.14, p = 0.711 by allele; rs763780: χ2 = 2.24, p = 0.326 by genotype, χ2 = 0.26, p = 0.609 by allele; rs4819554: χ2 = 1.79, p = 0.409 by genotype, χ2 = 1.46, p = 0.227 by allele). Levels of serum IL-17A and IL-17F were significantly decreased in gout patients (both p<0.001). However, no difference was observed in acute gout patients between different genotypic carriers of rs2275913 and rs763780 regarding serum IL-17A and IL-17F levels (p>0.05). Although the genetic variants in IL-17 we studied in this research do not appear to be involved in the development of gout in male Chinese Han individuals, the IL-17 cytokine family may participate in gouty inflammation in an undefined way, which requires further validation. [ABSTRACT FROM AUTHOR]