Benefits of uric acid-lowering medication after bariatric surgery in patients with gout.

BACKGROUND/PURPOSE: Patients with gout are at risk for increased serum uric acid (SUA) levels and gout attacks in the short term after undergoing bariatric surgery, and the purpose of this study was to evaluate the benefits of short-term treatment with uric acid-lowering medication after bariatric surgery for the control of gout attacks and SUA levels in patients with gout. METHODS: 71 patients who underwent SG from January 2020 to December 2022 were prospectively included. These patients were diagnosed with hyperuricemia before surgery and had a history of gout attacks. Patients were classified into a drug-treatment group (DTG, n = 32) and a non-drug-treatment group (NDTG, n = 39) according to whether they took uric acid-lowering medication after surgery. Changes in the number of gout attacks, body mass index (BMI), and SUA levels at 1 week, 1 month, 3 months, and 6 months after bariatric surgery were measured in both groups. RESULTS: In the DTG, 22 patients (68.8%) experienced an increase in SUA within 1 week, 3 patients (9.4%) had an acute attack of gout within the first month, and no patients had a gout attack thereafter. In the NDTG, 35 patients (89.7%) experienced an increase in SUA within 1 week, 7 patients (17.9%) had an acute gout attack within the first month, and 4 patients (10.3%) experienced gout attacks between month 1 and month 3 postoperatively. Both groups were free of gout attacks between the 3rd and 6th postoperative month and showed a significant decrease in SUA and BMI by the sixth month. CONCLUSION: In patients with gout, continued use of uric acid-lowering medication after bariatric surgery is beneficial in reducing the number of gout attacks and the risk of rising SUA.

Prevalence of hyperuricemia among type 2 diabetes mellitus patients in Africa: a systematic review and meta-analysis.

BACKGROUND: Hyperuricemia increases morbidity and mortality in type 2 diabetic individuals. It is linked to the expansion of diabetes and cardiovascular diseases indicators, as well as being a significant predictor of coronary artery disease. It also leads to a poor prognosis and increment of diabetic complications including diabetic neuropathy, retinopathy, and nephropathy. Therefore, this systematic review and meta-analysis was aimed to determine the pooled prevalence of hyperuricemia among type 2 diabetes mellitus patients in Africa. METHODS: We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. To identify relevant articles, we searched electronic databases such as PubMed, Google Scholar, African Journal Online, Science Direct, Embase, ResearchGate, Scopus, and Web of Sciences. The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Statistical analysis was performed using Stata 14.0 software. To evaluate heterogeneity, we utilized Cochran's Q test and I2 statistics. Publication bias was assessed through the examination of a funnel plot and Egger's test. The pooled prevalence was estimated using a random effect model. Furthermore, sub-group and sensitivity analyses were conducted. RESULTS: The overall pooled prevalence of hyperuricemia among type 2 diabetic patients in Africa was 27.28% (95% CI: 23.07, 31.49). The prevalence was highest in Central Africa 33.72% (95% CI: 23.49, 43.95), and lowest in North Africa 24.72% (95% CI: 14.38, 35.07). Regarding sex, the pooled prevalence of hyperuricemia among female and male type 2 diabetic patients was 28.02% (95% CI: 22.92, 33.48) and 28.20% (95% CI: 22.92, 33.48), respectively. CONCLUSION: This systematic review and meta-analysis showed a high prevalence of hyperuricemia among type 2 diabetic patients. So, regular screening and diagnosis of hyperuricemia required for preventing its pathological effects and contribution to chronic complications of diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (2022: CRD42022331279).

The efficacy and cost-impact of rasburicase 3†mg versus 6†mg for the management of tumor lysis syndrome: A multicenter analysis.

Purpose: Hyperuricemia is a complication arising from tumor lysis syndrome (TLS). Literature has shown that a single 3 mg dose was just as efficacious as a single 6 mg dose when the uric acid (UA) levels were ≤12 mg/dL. Here, we present a multi-center analysis rasburicase utilization and its effect on healthcare costs. Methods: This is a multi-center, retrospective analysis of adult cancer patients who were admitted to Methodist Le Bonheur Healthcare hospitals and received rasburicase from February 2020 to February 2021. The primary endpoint was to test whether rasburicase 3 mg had similar rates of uric acid normalization (defined as uric acid ≤7.5 mg/dL) within 24 h as a dose of 6 mg. Results: Seventy-nine patients were included in the study. While the baseline uric acid was lower in the 3 mg arm compared to the 6 mg arms, there was no difference in the uric acid normalization at 24 h between the 3 mg arm (95%) and 6 mg arm (82%) (p = 0.134). A cost-savings of over $300,000 annually can be achieved with the proposed protocol. Conclusion: A single, fixed rasburicase dose of 3 mg was effective in normalizing uric acid levels within 24 h, and is associated with significant cost-savings.

Individualized Homeopathic Medicines in Treatment of Hyperuricemia: Evaluation by Double-Blind, Randomized, Placebo-Controlled Trial.

INTRODUCTION: Hyperuricemia (HU) is a major health issue in India and across the globe. It increases the disease burden and hampers quality of life. This study was aimed at exploring the effects of individualized homeopathic medicines (IHMs) against placebo in the treatment of HU. METHODS: This double-blind, randomized, placebo-controlled trial was conducted on 60 patients suffering from HU in the outpatient department of D. N. De Homoeopathic Medical College and Hospital, Kolkata. Each patient received either IHMs or identical-looking placebos, along with advice on dietary modifications irrespective of codes. Serum uric acid (SUA) level was the primary outcome measure; the HU quality of life questionnaire (HUQLQ) and the Measure Yourself Medical Outcome Profile version 2 (MYMOP-2) were the secondary outcomes; all measured at baseline, and every month, up to 3 months. Group differences were examined by two-way (split-half) repeated-measures analysis of variance after adjusting for baseline differences. Significance level was set at p ≤0.05, two-tailed. RESULTS: The intention-to-treat sample (n = 58) was analyzed. Between-group differences in SUA levels (F 1, 56 = 13.833, p <0.001), HUQLQ scores (F 1, 56 = 32.982, p <0.001) and MYMOP-2 profile scores (F 1, 56 = 23.873, p <0.001) were statistically significant, favoring IHMs against placebos, with medium to large effect sizes. Calcarea carbonica and Pulsatilla nigricans were the most frequently prescribed medicines. No serious adverse events were reported from either of the groups. CONCLUSION: IHMs showed significantly better results than placebos in reducing SUA levels and improving quality of life in patients suffering from HU. TRIAL REGISTRATION: CTRI/2019/10/021503; UTN: U1111-1241-1431.

Prevalence and Outcomes Associated with Hyperuricemia in Hospitalized Patients with COVID-19.

INTRODUCTION: Coronavirus 2019 (COVID-19) can increase catabolism and result in hyperuricemia. Uric acid (UA) potentially causes kidney damage by alteration of renal autoregulation, inhibition of endothelial cell proliferation, cell apoptosis, activation of the pro-inflammatory cascade, and crystal deposition. Hyperuricemia in patients with COVID-19 may contribute to acute kidney injury (AKI) and poor outcomes. METHODS: We included 834 patients with COVID-19 who were >18 years old and hospitalized for >24 h in the Mount Sinai Health System and had at least 1 measurement of serum UA. We examined the association between the first serum UA level and development of acute kidney injury (AKI, defined by KDIGO criteria), major adverse kidney events (MAKE, defined by a composite of all-cause in-hospital mortality or dialysis or 100% increase in serum creatinine from baseline), as well as markers of inflammation and cardiac injury. RESULTS: Among the 834 patients, the median age was 66 years, 42% were women, and the median first serum UA was 5.9 mg/dL (interquartile range 4.5-8.8). Overall, 60% experienced AKI, 52% experienced MAKE, and 32% died during hospitalization. After adjusting for demographics, comorbidities, and laboratory values, a doubling in serum UA was associated with increased AKI (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.9-4.1), MAKE (OR 2.5, 95% CI 1.7-3.5), and in-hospital mortality (OR 1.7, 95% CI 1.3-2.3). Higher serum UA levels were independently associated with a higher level of procalcitonin (ß, 0.6; SE 0.2) and troponin I (ß, 1.2; SE 0.2) but were not associated with serum ferritin, C-reactive protein, and interleukin-6. CONCLUSION: In patients admitted to the hospital for COVID-19, higher serum UA levels were independently associated with AKI, MAKE, and in-hospital mortality in a dose-dependent manner. In addition, hyperuricemia was associated with higher procalcitonin and troponin I levels.

Rationale, design, demographics and baseline characteristics of the randomized, controlled, Phase 2b SAPPHIRE study of verinurad plus allopurinol in patients with chronic kidney disease and hyperuricaemia.

BACKGROUND: Verinurad is a human uric acid (UA) transporter (URAT1) inhibitor known to decrease serum UA (sUA) levels and that may reduce albuminuria. In a Phase 2a study (NCT03118739), treatment with verinurad + febuxostat lowered urine albumin-to-creatinine ratio (UACR) at 12 weeks by 39% (90% confidence interval 4-62%) among patients with Type 2 diabetes mellitus, hyperuricaemia and albuminuria. The Phase 2b, randomized, placebo-controlled Study of verinurAd and alloPurinol in Patients with cHronic kIdney disease and hyperuRicaEmia (SAPPHIRE; NCT03990363) will examine the effect of verinurad + allopurinol on albuminuria and estimated glomerular filtration rate (eGFR) slope among patients with chronic kidney disease (CKD) and hyperuricaemia. METHODS: Adults (≥18 years of age) with CKD, eGFR ≥25 mL/min/1.73 m2, UACR 30-5000 mg/g and sUA ≥6.0 mg/dL will be enrolled. Approximately 725 patients will be randomized 1:1:1:1:1 to 12, 7.5 or 3 mg verinurad + allopurinol, allopurinol or placebo. An 8-week dose-titration period will precede a 12-month treatment period; verinurad dose will be increased to 24 mg at Month 9 in a subset of patients in the 3 mg verinurad + allopurinol arm. The primary efficacy endpoint the is change from baseline in UACR at 6 months. Secondary efficacy endpoints include changes in UACR, eGFR and sUA from baseline at 6 and 12 months. CONCLUSIONS: This study will assess the combined clinical effect of verinurad + allopurinol on kidney function in patients with CKD, hyperuricaemia and albuminuria, and whether this combination confers renoprotection beyond standard-of-care.

Relationship between seaweeds consumption and hyperuricaemia in general adults: a Population-based study from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort study.

Seaweeds have numerous biologically active ingredients, such as polysaccharides, polyphenols and carotenoids, that are beneficial to human health. Although these benefits might be related to the synthesis, secretion or reabsorption of uric acid, no studies have explored the relationship between seaweeds consumption and hyperuricaemia (HUA) in the general population. The aim of this study was to investigate whether seaweeds consumption is related to HUA in a large-scale adult population. A cross-sectional study was conducted with 32 365 adults (17 328 men and 15 037 women) in Tianjin, People's Republic of China. Frequency of seaweeds consumption was assessed by a validated self-administered FFQ. HUA was defined as serum uric acid levels >420 µmol/L in men and >350 µmol/L in women. The association between seaweeds consumption and HUA was assessed by multiple logistic regression analysis. Restricted cubic spline functions were used for non-linearity tests. The prevalence of HUA in men and women was 21·17 % and 5·93 %, respectively. After adjustments for potential confounding factors, the OR (95 % CI) for HUA across seaweed consumption (g/1000 kcal per d) were 1·00 (reference) for level 1, 0·91 (95 % CI 0·81, 1·02) for level 2; 0·90 (95 % CI 0·81, 1·01) for level 3; 0·86 (95 % CI 0·78, 0·97) for level 4 in men and 0·90 (95 % CI 0·73, 1·10) for level 2; 0·82 (95 % CI 0·67, 1·00) for level 3; 0·84 (95 % CI 0·68, 1·03) for level 4 in women, respectively. A negative correlation between seaweeds consumption and HUA in males but not in females was observed. Further studies are needed to explore the causal relationship.

Higher dietary acid load is associated with hyperuricemia in Chinese adults: a case-control study.

BACKGROUND: This study aims to explore the association between dietary acid load and hyperuricemia in Chinese adults. METHODS: A case-control study was conducted. Adult participants with hyperuricemia were recruited as the cases and those without hyperuricemia were as the controls. Food consumption was evaluated by food frequency questionnaire (FFQ). Dietary acid load was assessed by potential renal acid load (PRAL) and net endogenous acid production (NEAP). Dietary acid load was divided into four levels: the first quartile (Q1), the second quartile (Q2), the third quartile (Q3) and the fourth quartile (Q4). Logistic regression model was applied for exploring the association between dietary acid load (PRAL and NEAP) and hyperuricemia. Odds ratio (OR) and its correspondence confidence interval (CI) were computed. RESULTS: A total of 290 participants were eligible in this study, in which there were 143 individuals in case group and 147 in control group. A higher level of PRAL was found to be associated with odds of hyperuricemia. ORs of hyperuricemia for Q2, Q3 and Q4 of PRAL were 2.74 (95%CI: 1.94 ~ 3.88, p-value: 0.004), 2.90 (95%CI: 2.05 ~ 4.10, p-value: 0.002) and 3.14 (95%CI: 2.22 ~ 4.45, p-value: 0.001), respectively. There was a positive association between elevated NEAP and hyperuricemia. OR of hyperuricemia for Q2 was not material significance (OR:1.54, 95%CI: 0.93 ~ 2.53, p-value: 0.210), however, ORs of hyperuricemia for Q3 (OR: 2.40, 95%CI: 1.70 ~ 3.38, p-value: 0.011) and Q4 (OR: 3.27, 95%CI: 2.31 ~ 4.62, p-value: 0.001) were statistically significant. CONCLUSION: Higher level of dietary acid load was found to be associated with hyperuricemia in Chinese adults, indicative of advocation of a well-balanced diet in this population.

High prevalence and low awareness of hyperuricemia in hypertensive patients among adults aged 50-79 years in Southwest China.

INTRODUCTION: This study was aimed to assess the prevalence of hyperuricemia and its associated risk factors among hypertensive patients in Southwest China. METHODS: From September 2013 to March 2014, a multistage, stratified sampling was conducted on 3505 hypertensive people aged 50-79 years who lived in urban communities within Chengdu and Chongqing, using a questionnaire and performing physical and biochemical measurements. RESULTS: In the study population, approximately 18.2% of all hypertensive participants had hyperuricemia (638/3505), with a prevalence rate of 21.5% in men and 16.2% in women (p < 0.05). Multivariate logistic regression analysis showed that aging, without spouse, current drinking, preferring hotpot, hypertriglyceridemia, BMI ≥ 25 kg/ m2, and central obesity were all positively correlated with hyperuricemia, whereas female gender was negatively correlated with hyperuricemia. The prevalence of hyperuricemia among hypertensive patients in urban adults aged 50-79 years in southwestern China was high, while levels of awareness were extremely low. DISCUSSION: Improved hyperuricemia health knowledge should be delivered to improve public awareness of the disease and it may need aggressive strategies aiming at the prevention and treatment of hyperuricemia. It is may necessary to encourage people to check blood uric acid levels when they first time to be diagnosed with hypertension, especially in the elderly.

Erosive Tophaceous Gouty Arthropathy of the Hand: A Case Report.

The presence of tophaceous gout in the hand is a classic finding seen in uncontrolled gout. Occasionally gouty tophi can be the initial physical finding in asymptomatic hyperuricemia. Composed of monosodium urate (MSU) crystals, gouty tophi can cause significant soft tissue and joint pathology. In addition, tophaceous gout and hyperuricemia are associated with increased mortality. We present a patient with tophaceous gout causing erosive arthropathy of the proximal interphalangeal (PIP) joint. The diagnosis and treatment for tophaceous gout is reviewed.

Antidiabetic Effect of Taxifolin in Cultured L6 Myotubes and Type 2 Diabetic Model KK-Ay/Ta Mice with Hyperglycemia and Hyperuricemia.

Muscle is the largest tissue in our body and plays an important role in glucose homeostasis and hence diabetes. In the present study, we examined the effects of taxifolin (TXF) on glucose metabolism in cultured L6 muscle cells (myotubes) and in type 2 diabetic (T2D) model KK-Ay/Ta mice. TXF dose-dependently increased glucose uptake (GU) in L6 myotubes under the condition of insulin absence. This increase in GU was partially, but significantly canceled by TXF treatment in combination with either LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), which phosphorylates protein kinase B (Akt) or Compound C, an inhibitor of 5'-adenosine monophosphate-activated protein kinase (AMPK). Furthermore, TXF was demonstrated to activate (=phosphorylate) both Akt and AMPK, and promote glucose transporter 4 (GLUT4) translocation to the plasma membrane from cytosol of L6 myotubes via both PI3K/Akt and AMPK signaling pathways. Based on these in vitro findings, we conducted an in vivo experiment in KK-Ay/Ta mice with hyperglycemia and hyperuricemia. Fasting plasma glucose, insulin, uric acid levels and an index of insulin resistance (HOMA-IR) increased significantly in the T2D model mice compared with normal ones. Such rises in the T2D state were significantly suppressed by oral administration of TXF for four weeks. These results suggest that TXF is a potent antihyperglycemic and antihyperuricemic phytochemical in the T2D state.

CD38 activation by monosodium urate crystals contributes to inflammatory responses in human and murine macrophages.

Cluster of differentiation (CD) 38, a major enzyme for nicotinamide adenine dinucleotide (NAD+) degradation, plays a key role in inflammation. Meanwhile, intracellular NAD+ decline is also associated with inflammatory responses. However, whether CD38 activation is involved in gouty inflammation has not been elucidated. The present study aimed to clarify the role of CD38 in monosodium urate crystals (MSU)-triggered inflammatory responses. The results showed that MSU crystals increased the protein expression of CD38 in time- and concentration-dependent manner in THP-1 macrophages and mouse bone marrow-derived macrophages (BMDMs). Moreover, intracellular NAD+ levels were reduced by MSU crystals along with the increased IL-1ß release. However, CD38 inhibition by 78c elevated intracellular NAD+ levels and suppressed IL-1ß release in MSU crystals-treated THP-1 macrophages and BMDMs. Interestingly, CD38 inhibition without significant elevation of intracellular NAD+ also decreased IL-1ß release driven by MSU crystals in THP-1 macrophages. In conclusion, the present study revealed that MSU crystals could activate CD38 with the ensuing intracellular NAD+ decline to promote inflammatory responses in THP-1 macrophages and BMDMs, while CD38 inhibition could suppress MSU crystals-triggered inflammatory responses, indicating that CD38 is a potential therapeutic target for gout.

Low expression of estrogen receptor ß in renal tubular epithelial cells may cause hyperuricemia in premenopausal patients with systemic lupus erythematosus.

We investigated the impact of estrogen receptor (ER) expression in renal tubular epithelial cells on serum uric acid (UA) levels in premenopausal patients with systemic lupus erythematosus (SLE). Thirty patients underwent renal biopsy: 18 with SLE (LN group) and 12 with IgA nephritis (IgAN group). ERs (ERα and ERß) in renal tubular epithelial cells were measured using immunohistochemistry. The ER expression levels of the two groups were compared, and the relationship between the expression of ERs and serum UA levels was analyzed. Mean serum UA levels in the LN group were significantly higher than those of the IgA nephropathy group, while the mean creatinine levels and GFRs of the two groups were similar. Pathological changes in the LN group were significantly more severe than those in the IgAN group. ERß was expressed in renal tubular epithelial cells in both groups, but not in the glomeruli. ERß expression in the LN group was significantly lower than that in the IgAN group. ERß expression scores significantly negatively correlated with serum UA levels. These findings suggest that the expression of ERß in premenopausal female SLE patients may cause hyperuricemia, and may subsequently promote glomerular damage, suggesting that ERß may be involved in UA excretion.

Serum albumin predicts hyperuricemia in patients with idiopathic membranous nephropathy.

AIM: The aim of the study was to examine the cross-sectional association between serum albumin and hyperuricemia (HU). MATERIALS AND METHODS: HU was defined as uric acid ≥ 420 umol/L for the male population and ≥ 357 umol/Lfor the female population. We reviewed the files of 216 consecutive patients with idiopathic membranous nephropathy treated at our hospital between 2010 and 2019. The correlation of serum albumin with hyperuricemia and the association between serum uric acid levels and the clinical of Idiopathic membranous nephropathy were assessed by statistical analysis. A multivariable logistic analysis model was applied to test the association after adjusting for a number of potential confounding factors. RESULTS: Triglyceride and serum albumin were higher in the group with hyperuricemia than in the group without hyperuricemia (p = 0.020, p < 0.001, respectively). As serum albumin rose to 1 g/L, the probability for hyperuricemia increased to 17% (adjusted II OR = 1.17, 95% CI (1.02, 1.35), p = 0.0294). A unit increase in serum albumin was associated with an increase of 6.64 g/L in uric acid (adjusted II ß = 6.64, p = 0.0135). Using tertile 1 (T1) for reference, the tertile 3 (T3) group was positively associated with both hyperuricemia (adjusted II OR = 44.21, 95% CI (12.76, 75.67), p = 0.0064) and uric acid (adjusted II ß = 98.64, p = 0.0116). The interaction test showed significant interactions between serum albumin and the body mass index (BMI) when hyperuricemia or uric acid were used to determine the outcomes. The participants with a BMI ≥ 25 kg/m2 had a higher OR between serum albumin and hyperuricemia and had a higher ß between serum albumin and uric acid than those with a BMI ≥ 25 kg/m2 (for hyperuricemia: OR = 1.01 vs. 1.18, p for interaction = 0.0056; for uric acid: ß = 0.96 vs. 6.23, p for interaction = 0.0154). The area under the ROC curve (AUC) was 0.7615 in the participants with a BMI ≥ 25 kg/m2. The sensitivity and specificity of this point were 47.37% and 95.83%, respectively. CONCLUSION: Our study showed that serum albumin was positively associated with hyperuricemia and uric acid, especially in obese subjects.

Association between retinol intake and hyperuricaemia in adults.

OBJECTIVE: Current evidences on the association between hyperuricaemia and retinol intake remain inconsistent. Furthermore, no known studies have investigated the relationship between hyperuricaemia and retinol intake from animal food and plant food separately. This study aimed to assess the relationship between different sources of retinol intake and risk of hyperuricaemia among US adults. DESIGN: Univariate and multivariate weighted logistic regression models and restricted cubic spline models were used to assess the associations of total, animal-derived and plant-derived retinol intakes with the risk of hyperuricaemia. Dietary retinol was measured through two 24-h dietary recall interviews. Hyperuricaemia was defined as serum uric acid level ≥7·0 and ≥6·0 mg/dl in men and women, respectively. SETTING: Data from the National Health and Nutrition Examination Survey 2009-2014 were used in this cross-sectional study. PARTICIPANTS: Overall, 12 869 participants aged ≥20 years were included. RESULTS: Compared with the lowest quintile, the multivariable OR of hyperuricaemia for the highest quintile intake of total, animal-derived and plant-derived retinol were 0·71 (95 % CI 0·52, 0·96), 0·76 (95 % CI 0·59, 0·96) and 0·92 (95 % CI 0·72, 1·17), respectively. The inverse association between dietary intake of total retinol and the risk of hyperuricaemia was observed in men. Dose-response analyses revealed a novel linear trend between the risk of hyperuricaemia and total, animal-derived retinol intake separately. CONCLUSIONS: Our findings indicated that intakes of total and animal-derived retinol were negatively associated with hyperuricaemia in US adults.

Nut intake and hyperuricemia risk in young adults.

OBJECTIVE: The relationship between dietary nut intake and hyperuricemia risk remains unclear. The aim of this study was to investigate the relationship between different nut intake and hyperuricemia risk with a cross-sectional study. DESIGN: A semi-quantitative FFQ was adopted to collect dietary information. Biochemical and anthropometric parameters were measured by standard methods. Multivariate-adjusted logistic regression models were implemented to analyse the relationship between individual nut intake and hyperuricemia risk. SETTING: Qingdao University in Shandong Province, China. PARTICIPANTS: During 2018-2019, a total of 14 056 undergraduates (6862 males and 7194 females) aged 15-25 years participated in the study. RESULTS: After adjusting for multiple confounding factors, compared with the lowest quartile, the highest quartile intakes of pine nut (95 % CI (0·51, 0·98)) was significantly associated with 29 % reduction in hyperuricemia risk, the highest quartile intake of walnut (OR = 0·78; 95 % CI (0·58, 1·05)) was marginally negatively associated with hyperuricemia risk. CONCLUSIONS: The present study showed that the relationships between intakes of different nuts and hyperuricemia risk were different. Increased dietary intakes of walnut and pine nut are negatively associated with the hyperuricemia.

Age difference in the combined effect of soda drinks consumption and body adiposity on hyperuricaemia in US adults.

OBJECTIVE: To evaluate age-related differences in the independent/combined association of added sugar intake from soda and body adiposity with hyperuricaemia in gender-stratified US adults. DESIGN: Consumption of added sugar from soda was calculated from 24-h dietary interviews and categorised into none, regular and excessive consumption. Hyperuricaemia was defined as serum uric acid levels >417 mmol/l in men and >357 mmol/l in women. Multiple regression models with interaction terms and logistic models adjusted for covariates were conducted under survey-data modules. SETTING: National Health and Nutrition Examination Survey during 2007-2016. PARTICIPANTS: 15 338 adults without gout, failing kidneys, an estimated glomerular filtration rate < 30 or diabetes were selected. RESULTS: The age-stratified prevalence rate of hyperuricaemia was 18·8-20·4 % in males and 6·8-17·3 % in females. Hyperuricaemia prevalence of approximately 50 % was observed in young and middle age males who consumed excessive added sugar from soda. Excessive added sugar intake was observed to be associated with 1·5- to 2·0-fold and 2·0- to 2·3-fold increased risk of the probability of hyperuricaemia in young and middle age males and middle age females, respectively. Study participants, regardless of age or gender, who were obese and consumed excessive added sugar from soda had the highest risk of having hyperuricaemia. CONCLUSIONS: Our study revealed that the association between hyperuricaemia and consumption of excessive added sugar from soda may vary by age and gender. Obese adults who consumed excessive added sugar from soda had the highest risk of hyperuricaemia, a finding that was found across all age-specific groups for both genders.

Hereditary hemochromatosis disrupts uric acid homeostasis and causes hyperuricemia via altered expression/activity of xanthine oxidase and ABCG2.

Hereditary hemochromatosis (HH) is mostly caused by mutations in the iron-regulatory gene HFE. The disease is associated with iron overload, resulting in liver cirrhosis/cancer, cardiomegaly, kidney dysfunction, diabetes, and arthritis. Fe2+-induced oxidative damage is suspected in the etiology of these symptoms. Here we examined, using Hfe-/- mice, whether disruption of uric acid (UA) homeostasis plays any role in HH-associated arthritis. We detected elevated levels of UA in serum and intestine in Hfe-/- mice compared with controls. Though the expression of xanthine oxidase, which generates UA, was not different in liver and intestine between wild type and Hfe-/- mice, the enzymatic activity was higher in Hfe-/- mice. We then examined various transporters involved in UA absorption/excretion. Glut9 expression did not change; however, there was an increase in Mrp4 and a decrease in Abcg2 in Hfe-/- mice. As ABCG2 mediates intestinal excretion of UA and mutations in ABCG2 cause hyperuricemia, we examined the potential connection between iron and ABCG2. We found p53-responsive elements in hABCG2 promoter and confirmed with chromatin immunoprecipitation that p53 binds to this promoter. p53 protein was reduced in Hfe-/- mouse intestine. p53 is a heme-binding protein and p53-heme complex is subjected to proteasomal degradation. We conclude that iron/heme overload in HH increases xanthine oxidase activity and also promotes p53 degradation resulting in decreased ABCG2 expression. As a result, systemic UA production is increased and intestinal excretion of UA via ABCG2 is decreased, causing serum and tissue accumulation of UA, a potential factor in the etiology of HH-associated arthritis.

Inter-relationship of risk factors and pathways associated with chronic kidney disease in patients with type 2 diabetes mellitus: a structural equation modelling analysis.

OBJECTIVES: Diabetes mellitus is the most common cause of chronic kidney disease (CKD); however, the inter-relationships and pathogenetic mechanisms among risk factors are still largely unknown. Structural equation modelling (SEM) was applied to test a hypothesis of causal pathways related to CKD in patients with type 2 diabetes mellitus (T2DM). STUDY DESIGN: This is a prospective observational study. METHODS: A total of 3395 patients with T2DM were enrolled in this study. A hypothesised SEM was applied to assess associations among demographic data, diabetic self-management behaviours, diabetes control, lifestyle, psycho-social, chronic inflammation factors, anthropometric and metabolic variables simultaneously and the risk of CKD. RESULTS: Demographic data (including education, marital status and mini-mental state examination score) (-0.075), white blood cell count (0.084), high blood pressure (0.144), World Health Organisation (WHO) 5 well-being index (-0.082), diabetes control (0.099), triglyceride (0.091) and uric acid (0.282) levels had direct effects on the risk of CKD. The final model could explain 26% of the variability in baseline CKD status. In addition, the same direct and specific indirect factors at baseline CKD status analysis contributed to the risk of CKD at the 12-month follow-up. The final model could explain 31% of the variability in the risk of CKD at the 12-month follow-up. CONCLUSIONS: This study investigates associations between factors obtained from real-world daily practice and CKD status simultaneously and delineates the potential pathways and inter-relationships of the risk factors that contribute to the development of CKD in patients with T2DM.

The Role of ABCG2 in the Pathogenesis of Primary Hyperuricemia and Gout-An Update.

Urate homeostasis in humans is a complex and highly heritable process that involves i.e., metabolic urate biosynthesis, renal urate reabsorption, as well as renal and extrarenal urate excretion. Importantly, disturbances in urate excretion are a common cause of hyperuricemia and gout. The majority of urate is eliminated by glomerular filtration in the kidney followed by an, as yet, not fully elucidated interplay of multiple transporters involved in the reabsorption or excretion of urate in the succeeding segments of the nephron. In this context, genome-wide association studies and subsequent functional analyses have identified the ATP-binding cassette (ABC) transporter ABCG2 as an important urate transporter and have highlighted the role of single nucleotide polymorphisms (SNPs) in the pathogenesis of reduced cellular urate efflux, hyperuricemia, and early-onset gout. Recent publications also suggest that ABCG2 is particularly involved in intestinal urate elimination and thus may represent an interesting new target for pharmacotherapeutic intervention in hyperuricemia and gout. In this review, we specifically address the involvement of ABCG2 in renal and extrarenal urate elimination. In addition, we will shed light on newly identified polymorphisms in ABCG2 associated with early-onset gout.