High Serum Uric Levels Research Articles

Joint association of serum urate and healthy diet with chronic obstructive pulmonary disease incidence: results from the UK Biobank study.

Background: The role of serum urate (SU) levels in the development of chronic obstructive pulmonary disease (COPD) remains a topic of debate, and it is unclear whether a healthy diet can mitigate the impact of SU on COPD risk. The objective of this study is to examine whether and to what extent a healthy diet can reduce the risk of COPD in relation to SU levels. Methods: The cohort analysis included 155 403 participants from the UK Biobank. SU levels were measured at the time of recruitment. A healthy diet score was calculated based on the consumption of vegetables, fruits, fish, processed meats, unprocessed red meat, whole grains, and refined grains. The Cox proportional hazards model was used to analyze the associations between SU levels, a healthy diet score, and the risk of COPD. Results: During a follow-up period of 1 409 969 person-years, 2918 incident cases of COPD were identified. Compared with the lowest SU level group, the hazard ratio (HR) and 95% confidence interval (CI) for COPD were 1.17 (1.03, 1.34) for participants with the highest SU level (hyperuricemia), indicating a positive association. Additionally, a dose-response relationship was observed between SU levels and the incidence of COPD (P-value for overall <0.0001). In the combined effect analysis, compared to individuals with high SU (hyperuricemia) + a low diet score (diet score <4), those with normal SU + a high diet score (diet score ≥4) had a HR (95% CI) of 0.75 (0.65, 0.87) for COPD. Conclusions: In summary, there is a positive association between SU levels and the risk of COPD. Furthermore, a healthier diet can mitigate the risk of COPD associated with high SU levels.

Cohort study investigating gout flares and management in UK general practice

BackgroundGout is the most common inflammatory arthritis and is almost exclusively managed in primary care, however the course and severity of the condition is variable and poorly characterised. This research aims improve understanding about the frequency of, and factors associated with, gout flares in the UK and characterise the factors associated with the initiation of ULT.MethodsUsing the Clinical Practice Research Database, patients with a coded incident gout diagnosis without a prior prescription for urate-lowering therapy (ULT) were identified. Gout flares post diagnosis and ULT initiation were identified through prescribing and coded data. Patient characteristics, co-morbidities and co-prescribing were co-variants. Factors associated with gout flares and ULT initiation were analysed using cox-proportional hazard model and logistic regression.ResultsFifty-one thousand seven hundred eighty-four patients were identified: 18,605 (35.9%, 95%CI 35.5–36.3%) had experienced ≥ 1 recurrent flare, 17.4% (95%CI 17.1–17.8%) within 12 months of diagnosis. Male sex, black ethnicity, higher BMI, heart failure, CKD, CVD and diuretic use were associated with flares, with the highest HR seen with high serum urate levels (≥ 540 µmol/L HR 4.63, 95%CI 4.03–5.31). ULT initiation was associated with similar variables, although higher alcohol intake and older age were associated with lower odds of ULT initiation but were not associated with flares. ULT was initiated in 27.7% (95%CI 27.3–28.0%): 5.7% (95%CI 5.5–5.9%) within 12 months of diagnosis. ULT initiation rates were higher in patients with recurrent flares.ConclusionApproximately one in six people with incident gout had a second flare within 12 months. Factors associated with flare recurrence and ULT initiation were similar, but ULT initiation occurred later after diagnosis than previously thought.

New xanthine oxidase inhibitor from white mulberry (Morus alba L.) – anti-gout prospective study

Abstract In recent years, Morus sp. (mulberry) has acquired a special importance due to its phytochemical composition and its beneficial effects on human health, including antioxidant, anticancer, antidiabetic and immuno-modulatory effects. The various parts of Morus sp., such as its fruits, leaves, twigs, and roots, are recognized as abundant sources of secondary metabolites, with the leaves containing significant amounts of glycosylated flavonols like quercetin and kaempferol, along with chlorogenic acid as the primary phenolic compound. Overall, it can be considered a multi utility plant and can be exploited as an alternative therapy in various ailments. Xanthine oxidase (XO) is the key enzyme for high serum urate levels which is the main cause of developing gout. Under the urate lowering therapy, allopurinol and febuxostat are the main XO inhibitors used to treat gout. However, mild to severe side effects of these synthetic XO inhibitors lead to finding an effective natural alternative without having any side effects. The present study was designed to find out phytochemical analysis and antigout properties of leaves of white mulberry plant. The phytochemical analysis was performed on quantitative and qualitative basis. The qualitative basis indicated the presence of alkaloids, glycosides, flavonoids, steroids, tannins, saponins and Anthraquinone. Biochemical regulation of extracts on anti-gout property using XO inhibition study. Microbial XO was isolated from the Bacillus pumilus to study the anti-gout effects of plant extracts qualitatively on xanthine – NBT plate. Additionally, image analysis studies revealed more clear aspects toward the inhibition studies by plant extracts. The XO activity observed varied from 2.89 to 13.80 μM of uric acid formed/min/ml of enzyme used. Ethanolic extract of mulberry leaves (EEML) showed higher XO inhibition than allopurinol. This is associated with its total polyphenol content, which ranged from 81.25 to 103.12 mg GAE/g of dried extract used, as reported in the case of EEML. The present study is the very first report of relating polyphenol content of EEML with the anti-gout property. EEML is a potential candidate for anti-gout property due to the presence of higher amounts of total polyphenol content and B. pumilus is the best source to extract microbial XO.

Differences in the Association Between Alcoholic Beverage Type and Serum Urate Levels Using Standardized Ethanol Content

Differences have been observed in the association of serum urate levels with consumption of different types of alcoholic beverages. However, previous studies have not standardized the unit of intake for ethanol content, and only limited types of alcoholic beverages have been evaluated. To examine differences in the association of serum urate levels with various types of alcoholic beverages when their intakes are standardized for ethanol content. This retrospective cross-sectional study was conducted using data from participants aged 20 years or older who completed a medical checkup at St Luke's International University in Japan between October 1, 2012, and October 31, 2021. Participant demographics, blood test results, and lifestyle questionnaire data were used as covariates. Analysis was performed in December 2021. Consumption of alcoholic beverages, including beer, sake (rice wine), shochu (Japanese spirit), wine, and whiskey. Serum urate levels were measured during the medical checkup. The beverage unit was standardized to 1 standard drink, which contained 20 g of ethanol. Multivariable linear regression including interaction terms of alcohol consumption and dominant alcoholic beverage was performed. This study included 78 153 participants. Their mean (SD) age was 47.6 (12.8) years; 36 463 (46.7%) were men and 41 690 were women (53.3%). A total of 45 755 participants (58.5%) were regular alcohol drinkers. Consistent associations of serum urate levels with alcohol consumption were observed in the beer-dominant group, with β coefficients (for 1 standard drink per day) of 0.14 mg/dL (95% CI, 0.11-0.17 mg/dL; P < .001) for men and 0.23 mg/dL (95% CI, 0.20-0.26 mg/dL; P < .001) for women. A moderate increase in serum urate levels was observed in the wine-dominant group compared with a modest and nonsignificant increase in the sake-dominant group, with β coefficients (for 1 standard drink per day) for the latter group of 0.05 mg/dL (95% CI, -0.01 to 0.10; P = .10) for men and 0.04 mg/dL (95% CI, -0.05 to 0.14 mg/dL; P = .38) for women. Restricted cubic splines showed different patterns in associations of serum urate levels with ethanol intake by dominant alcoholic beverages. The results of this study suggest that the extent of the association of serum urate levels with alcohol intake was different for alcoholic beverages even after ethanol content was standardized. Higher beer consumption among men and women was consistently associated with higher serum urate levels, whereas sake was not associated with changes in serum urate levels. Therefore, alcoholic beverage type, in addition to ethanol content, should be considered as a factor contributing to hyperuricemia.

Detection of Monosodium Urate Crystal of Hand and Wrist in Suspected Gouty Arthritis Patients on Dual-Energy CT and Relationship with Serum Urate Level

We retrospectively investigated the characteristics of patients with monosodium urate (MSU) deposits of the hand and wrist on dual-energy CT (DECT) compared to those without. We also attempted to determine the pattern of MSU distribution in DECT. In total, 93 patients were included who had undergone DECT for evaluation of the hand or wrist pain under the clinical impression of gouty arthritis. The total volume of MSU deposits on DECT was calculated and the pattern of MSU distribution on DECT was analyzed. Also, the level of the serum urate at the time of DECT and the highest level of the serum urate of the patients were obtained from their records and the relationship between MSU and serum urate level was evaluated. The range of the volume of MSU deposits on DECT was 0.01-16.11 cm3 (average: 1.07 cm3). The average level of serum urate was significantly higher in the MSU positive group than that in the MSU negative group. MSU deposits were most frequently observed in the wrists followed by fingers and digitorum tendons. On DECT, MSU deposits were most frequently detected in the wrist and related with high serum urate level.

Impact of ABCG2 Gene Polymorphism on the Predisposition to Psoriasis.

Psoriasis is a chronic inflammatory disease which is caused by the interaction between genetic and environmental factors. Evidence shows an association of psoriasis with co-morbidities including cardiovascular diseases, metabolic syndrome and hyperuricemia. Genome-wide association studies have revealed that the ABCG2 gene encoding ATP-binding cassette G2 protein was associated with inflammation and higher serum urate concentrations. In this study, we aimed to evaluate the role of ABCG2 gene polymorphisms on the susceptibility to psoriasis. The genotype distribution of two ABCG2 single nucleotide polymorphisms (SNPs), rs2231142 and rs2231137, was examined in 410 psoriasis patients and 1,089 gender-matched non-psoriasis controls. We found that heterozygotes (GT) for rs2231142 was associated with a decreased risk of psoriasis (p = 0.001; adjusted OR = 0.532; 95% CI, 0.370–0.765) after adjusting for age, as compared with homozygotes for the major allele (GG). Subjects who carried at least one polymorphic allele (homozygote or heterozygote for the minor allele) were less susceptible to psoriasis (p = 0.002; adjusted OR = 0.594; 95% CI, 0.249–0.823) and bearing higher serum urate levels (p = 0.026) than those homozygous for the major allele. Our results indicated that the ABCG2 gene polymorphism was associated with the risk of psoriasis.

What is the diagnostic value of dual-energy computed tomography in patients with clinical diagnosis of gout?

ObjectivesTo investigate the frequency of monosodium urate (MSU) crystal deposits on dual-energy computed tomography (DECT) in patients with clinical diagnosis of gout and the factors associated MSU crystal positivity.MethodsThis study was conducted in patients with clinical diagnosis of gout who underwent DECT. Clinical features were compared between patients with positive and those with negative DECT results. A logistic regression analysis was performed to determine the factors associated with MSU crystal positivity on DECT.ResultsA total of 148 patients with clinical diagnosis of gout were included, and MSU crystal deposition on DECT was observed in 64 patients (43.3%). The patients with positive DECT results were more likely to have renal insufficiency, longer disease duration, and higher serum urate level than those with negative. In the multivariable analysis, first gout attack (odds ratio 0.462; 95% confidence interval 0.229–0.931, p = 0.031) was associated with a less likely MSU crystal deposit-positive DECT result. In the subgroup analysis of patients with first attack, serum urate level > 8 mg/dL was associated with DECT positivity.ConclusionOf the patients with clinical diagnosis of gout, those with renal insufficiency, longer disease duration, and high serum urate level were more likely to be positive of gout on DECT. First gout attack was associated with less likely to be positive for MSU crystal on DECT. Thus, performing DECT scan in the selected patients who had characteristics that highly probability of DECT positivity could increase positive predictive value.

Higher Serum Urate Levels Are Associated With an Increased Risk for Sudden Cardiac Death.

To determine the association of serum urate (SU) levels with sudden cardiac death and incident coronary heart disease (CHD), separately, among adults without a history of CHD. We conducted a case-cohort analysis of Black and White participants aged ≥ 45 years enrolled in the REason for Geographic And Racial Differences in Stroke (REGARDS) study without a history of CHD at baseline between 2003 and 2007. Participants were followed for sudden cardiac death or incident CHD (i.e., myocardial infarction [MI] or death from CHD excluding sudden cardiac death) through December 31, 2013. Baseline SU was measured in a random sample of participants (n = 840) and among participants who experienced sudden cardiac death (n = 235) or incident CHD (n = 851) during follow-up. Participants with higher SU levels were older and more likely to be male or Black. The crude HR (95% CI) per 1 mg/dL higher SU level was 1.26 (1.14-1.40) for sudden cardiac death and 1.17 (1.09-1.26) for incident CHD. After adjustment for age, sex, race, and cardiovascular risk factors, the HR (95% CI) per 1 mg/dL higher SU level was 1.19 (1.03-1.37) for sudden cardiac death and 1.05 (0.96-1.15) for incident CHD. HRs for sudden cardiac death were numerically higher among participants aged 45-64 vs ≥ 65 years, without vs with diabetes, and among those of White vs Black race, although P values for effect modification were all ≥ 0.05. Higher SU levels were associated with an increased risk for sudden cardiac death but not with incident CHD.

DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function

BackgroundThe difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies.ResultsWe identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E−03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang’s 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (β = − 0.12, 95% CI = [− 0.16, − 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E−08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (β = 0.12 [0.07, 0.16], p = 2.08E−06). The “first-generation” clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria.ConclusionDNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease.

Non-Genetic Risk Factors for Parkinson's Disease: An Overview of 46 Systematic Reviews.

Background:Numerous systematic reviews (SRs) and meta-analyses on non-genetic risk factors for Parkinson’s disease (PD) development have been published with inconsistent conclusions.Objective:This overview of SRs aimed to summarize evidence on non-genetic factors for the development of PD from the published SRs, and explore the reasons behind the conflicting results.Methods:Three international databases were searched for SRs with meta-analyses summarized evidence on non-genetic factors for PD development. The Assessing the Methodological Quality of Systematic Reviews 2 tool was used to appraise the methodological quality of included SRs. Pooled effect estimations were extracted from each meta-analysis.Results:Forty-six SRs covered six categories, and more than 80 factors were included in this overview. Thirty-nine SRs (84.7%) were judged to be of critically low methodological quality. Evidence from prospective studies showed that physical activity, smoking, coffee, caffeine, tea, fat intake, ibuprofen use, calcium channel blocker use, statin use, thiazolidinediones, and high serum urate levels significantly reduced the risk of PD, while dairy intake, diabetes, hormone replacement therapy, depression, mood disorder, bipolar disorder, and aspirin use significantly increased the risk of PD. Differences in study designs (e.g., cohort studies, case-control studies) accounted for the conflicting results among included SRs.Conclusion:Modifiable lifestyle factors such as physical activity and tea and coffee drinking may reduce the risk of PD, which may offer PD prevention strategies and hypotheses for future research. However, the designs of primary studies on PD risk factors and related SRs need to be improved and harmonized.

High-Protein Diet Induces Hyperuricemia in a New Animal Model for Studying Human Gout.

Hyperuricemia is a central risk factor for gout and increases the risk for other chronic diseases, including cardiometabolic disease, kidney disease, and hypertension. Overproduction of urate is one of the main reasons for hyperuricemia, and dietary factors including seafoods, meats, and drinking are contributed to the development of it. However, the lack of a suitable animal model for urate metabolism is one of the main reasons for the delay and limitations of hyperuricemia research. Combining evolutionary biological studies and clinical studies, we conclude that chicken is a preferred animal model for hyperuricemia. Thus, we provided chickens a high-protein diet (HPD) to evaluate the changes in the serum urate levels in chickens. In our study, the HPD increased the serum urate level and maintained it at a long-term high level in chickens. Long-term high serum urate levels induced an abnormal chicken claw morphology and the precipitation of monosodium urate (MSU) in joint synovial fluid. In addition, a long-term HPD also decreased the glomerular filtration rate and induced mild renal injury. Most importantly, allopurinol and probenecid displayed the positive effects in decreasing serum urate and then attenuated hyperuricemia in chicken model. These findings provide a novel model for hyperuricemia and a new opportunity to further investigate the effects of long-term hyperuricemia on other metabolic diseases.

Abstract P110: High Serum Urate Levels are Associated With an Increased Risk for Sudden Cardiac Death in the Reasons for Geographic and Racial Differences in Stroke (regards) Study

Background: Higher serum urate (SU) levels were shown to causally increase the risk for sudden cardiac death (SCD) in a Mendelian randomization analysis of white adults, most of whom had coronary heart disease (CHD). It is unclear if these results are generalizable to more racially diverse adults without CHD. Objective: To assess the risk for SCD and incident CHD associated with SU levels in adults without a history of CHD using data from a large, population-based cohort of US black and white men and women ≥45 years of age, the REason for Geographic And Racial Differences in Stroke (REGARDS) study. Methods: We conducted a case-cohort analysis of REGARDS study participants without a history of CHD at baseline between 2003 and 2007. Participants were followed for SCD or incident CHD (i.e., myocardial infarction or CHD death excluding SCD) from baseline through December 31, 2013. Baseline SU levels were measured in a random sample of participants (n=840) and among 235 participants with SCD and 851 participants with incident CHD. Results: Participants with higher SU levels were older and more likely to be black and male. The crude hazard ratio (95%CI) per 1 mg/dL higher SU level was 1.26 (1.14, 1.40) for SCD and 1.17 (1.09, 1.26) for incident CHD. Analyses modeling SU levels using splines supported that these associations were linear. After multivariable adjustment, higher SU levels remained associated with an increased risk for SCD, but not for incident CHD ( Table ). There was no effect modification in the association of SU levels with SCD or incident CHD by either age, gender, race or chronic kidney disease. However, the increased risk for SCD associated with higher SU levels was present in whites but not among blacks. Limitations: The study has limited statistical power for subgroup comparisons. Race differences in the association between SU levels and SCD require further investigation. Conclusions: In adults without a history of CHD, higher SU levels appear to be an independent risk factor for SCD, but no association was detected with incident CHD.

Spectrum and dosing of urate-lowering drugs in a large cohort of chronic kidney disease patients and their effect on serum urate levels: a cross-sectional analysis from the German Chronic Kidney Disease study.

BackgroundDespite a plethora of studies on the effect of urate-lowering therapy (ULT) in patients with chronic kidney disease (CKD), current guidelines on the treatment of hyperuricaemia and gout vary, especially concerning the need for dose adjustment of allopurinol, whose main metabolite is accumulating with declining renal function. Data on allopurinol dosing and its relationship to renal function, co-medication and sex and the resulting urate level in large cohorts are missing.MethodsWe studied a subgroup of 2378 patients of the German Chronic Kidney Disease (GCKD) study to determine prescription patterns of ULT among CKD patients under nephrological care and the relationship of ULT dose to urate levels. Prescription and dosing of ULT were manually abstracted from the patient’s paper charts at the baseline visit, in which all currently used medications and their dosing were recorded.ResultsIn this cohort, 39.6% were women, the mean estimated glomerular filtration rate (eGFR) was 51.3 ± 19.3 mL/min/1.73 m2 and the mean age was 59.0 ± 12.4 years. Of the 2378 examined patients, 666 (28.0%) received ULT. The dose of ULT was available for 572 patients. The main ULT agent was allopurinol (94.4%), followed by febuxostat (2.9%) and benzbromarone (2.6%). Of the 540 patients who used allopurinol with a reported daily dose, 480 had an eGFR <60 mL/min/1.73 m2 and 320 had an eGFR <45 mL/min/1.73 m2, 31.5% of the latter (n = 101) received a dose >150 mg/day, the recommended maximal dose for this level of eGFR. The prescribed dose was not related to eGFR: the median eGFR for patients taking 100, 150 and 300 mg/day was 40 [interquartile range (IQR) 32–49], 43 (34–52) and 42 (35–54) mL/min/1.73 m2, respectively. Patients with lower doses of allopurinol had higher serum urate levels than patients with higher (than recommended) allopurinol doses. Sex, alcohol intake, eGFR, use of diuretics and treatment with allopurinol were independent determinants of serum urate levels in multivariate regression analysis.ConclusionsThe most frequently used drug to lower serum urate levels in this CKD cohort was allopurinol. Even in patients regularly seen by nephrologists, the dose of allopurinol is often not adjusted to the current eGFR. Patients with higher ULT doses achieved better control of their serum urate levels. Lowering of serum urate in CKD patients requires balancing potential adverse effects of allopurinol with suboptimal control of serum urate levels.

Genetically determined serum urate levels and cardiovascular and other diseases in UK Biobank cohort: A phenome-wide mendelian randomization study.

BackgroundThe role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance.Methods and findingsA phenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic model (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 unrelated White British individuals (54% female) in the UK Biobank who were aged 40–69 years (mean age, 56.87; SD, 7.99) when recruited from 2006 to 2010. Mendelian randomization (MR) analyses were performed to replicate significant findings using various genome-wide association study (GWAS) consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effects on metabolic traits of the genetic variants used as instruments for urate. PheWAS analysis, examining the association with 1,431 disease outcomes, identified 13 distinct phecodes representing 4 disease groups (inflammatory polyarthropathies, hypertensive disease, circulatory disease, and metabolic disorders) and 9 disease outcomes (gout, gouty arthropathy, pyogenic arthritis, essential hypertension, coronary atherosclerosis, ischemic heart disease, chronic ischemic heart disease, myocardial infarction, and hypercholesterolemia) that were associated with genetically determined serum urate levels after multiple testing correction (p < 3.35 × 10−4). TreeWAS analysis, examining 10,750 ICD-10 diagnostic terms, identified more sub-phenotypes of cardiovascular and cerebrovascular diseases (e.g., angina pectoris, heart failure, cerebral infarction). MR analysis successfully replicated the association with gout, hypertension, heart diseases, and blood lipid levels but indicated the existence of genetic pleiotropy. Sensitivity analyses support an inference that pleiotropic effects of genetic variants on urate and metabolic traits contribute to the observational associations with CVDs. The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and possible misclassification of cases for mild disease that did not require hospitalization.ConclusionIn this study, high serum urate levels were found to be associated with increased risk of different types of cardiac events. The finding of genetic pleiotropy indicates the existence of common upstream pathological elements influencing both urate and metabolic traits, and this may suggest new opportunities and challenges for developing drugs targeting a common mediator that would be beneficial for both the treatment of gout and the prevention of cardiovascular comorbidities.

Association between uric acid and coron ary collateral circulation in stable coronary artery disease patients

Objective The aim of this study was to investigate the association between serum uric acid levels and the development of coronary collateral circulation (CCC) in patients with stable coronary artery disease. Background Serum uric acid can cause atherosclerosis. High serum uric acid levels may be associated with poor CCC in patients with stable coronary artery disease. Patients and methods A cross-sectional study was carried out on 100 patients with stable CAD who underwent coronary angiography and documented total occlusion in one or more of the major coronary arteries in Cardiovascular Department Menoufia University Hospital during the period from 1 February 2016 to 30 January 2017. Development of CCC will be graded according to the Cohen–Rentrop method: grades 2–3 will be classified as good CCC (group A) and grades 0–1 as poor CCC (group B). Results A significant relationship between high level of serum uric acid and poor coronary collaterals was observed. Mean value of uric acid in group A was 4.72 ± 1.69 mg/dl and mean value of uric acid in group B was 6.68 ± 2.36 mg/dl (P Conclusion The measurement of uric acid level provides a good predictor of poor CCC in stable coronary artery disease patients.

Recapture and improved outcome of pegloticase response with methotrexate–A report of two cases and review of the literature

IntroductionPegloticase is a PEGylated uric acid specific enzyme indicated for the treatment of refractory gout. Anti-pegloticase antibodies contribute to high discontinuation rates, increased risk of infusion reactions, and early loss of drug efficacy. ObjectiveTo describe the use of methotrexate to recapture function of pegloticase after development of anti-drug antibodies while treating gout. MethodsWe report two cases of using methotrexate as an adjunct to treatment with pegloticase for refractory tophaceous gout. We also present the results of a literature review on the use of concomitant immunosuppressive therapy with pegloticase to prevent anti-pegloticase antibody development. ResultsPatient A, a 55-year-old man with a history of tophaceous gout, was treated with pegloticase but developed high serum urate(sUA) levels prior to his third infusion. Adjunctive treatment with methotrexate restored pegloticase response and the patient's sUA levels decreased, and remained low for the remainder of his treatment.Patient B, a 36-year-old man with a history of tophaceous gout, was treated with pegloticase. Oral methotrexate was initiated at the first infusion. Low sUA levels were achieved but increased after a lapse in methotrexate compliance. Re-initiation of methotrexate restored pegloticase response and the patient tolerated subsequent infusions.Literature review identified three reports of successful use of concomitant pegloticase and immunosuppressive therapy for refractory tophaceous gout, including an open label trial with a subset of 7 transplant recipients, an additional case study of pegloticase treatment with one transplant recipient, and a case study of pegloticase administered with low-dose azathioprine. ConclusionProphylactic use of immunosuppressive therapy with pegloticase may enable sustained treatment and improve outcomes. Additionally, immunosuppressive therapy seems to show the ability to recapture pegloticase response after development of anti-drug antibodies. The use of immunosuppressants to prevent anti-drug antibody formation, recapture pegloticase efficacy, and reduce discontinuation rates warrants further study.

Ferric reducing ability of plasma and assessment of selected plasma antioxidants in adults with celiac disease.

Oxidative stress with an excessive free radical production and a reduction in the activity of protective antioxidants is considered as one of the mechanisms responsible for gluten toxicity. However, its role in celiac disease (CD) is unclear. Evaluation of plasma nonenzymatic antioxidant capacity in patients with CD (both untreated patients and those receiving gluten-free diet [GFD]) by measuring the ferric reducing ability of plasma (FRAP) as well as assessing selected plasma antioxidants. The study included 169 adult patients: 48 patients with untreated active CD, 72 patients with CD on a GFD, and 49 healthy controls. In each group, we measured the serum levels of selected antioxidants (uric acid, bilirubin, albumin, and vitamin E) and used the FRAP assay to assess the total antioxidant capacity (TAC) of plasma. In each patient, serological and histopathological activity of CD was also evaluated. There were no significant differences in the TAC of plasma measured with the FRAP assay between the study groups. Patients with CD had higher uric acid levels compared with controls (p <0.001), while bilirubin levels were lower in patients with active disease than in controls (p <0.05). Serum vitamin E levels were lower in all patients with CD compared with controls (p <0.01). The FRAP assay is not the method of choice for assessing the TAC of plasma in patients with CD. Owing to high serum uric acid levels, the FRAP assay results in these patients may be overestimated despite the reduced levels of other plasma antioxidants.

Nephrolithiasis among male patients with newly diagnosed gout.

An elevated serum urate level is recognised as a cause of gouty arthritis and uric acid stone. The level of serum uric acid that accelerates kidney stone formation, however, has not yet been clarified. This study aimed to find out if a high serum urate level is associated with nephrolithiasis. Patients were recruited from the rheumatology clinic of Taipei City Hospital (Renai and Zhongxing branches) in Taiwan from March 2015 to February 2016. A total of 120 Chinese male patients with newly diagnosed gout and serum urate concentration of >7 mg/dL and no history of kidney stones were divided into two groups according to their serum urate level: <10 mg/dL (group 1, n=80) and ≥10 mg/dL (group 2, n=40). The mean body mass index, blood urea nitrogen level, creatinine level, urinary pH, and kidney ultrasonography were compared between the two groups. There were no significant differences in blood urea nitrogen or creatinine level between the two groups. The urine pH in both groups was similar and not statistically significant. Kidney stone formation was detected via ultrasonography in 6.3% (5/80) and 82.5% (33/40) of patients in groups 1 and 2, respectively (P<0.05). A serum urate level of ≥10 mg/dL may precipitate nephrolithiasis. Further studies are warranted to substantiate the relationship between serum urate level and kidney stone formation.

Association of serum uric acid levels with the risk of development or progression of albuminuria among Japanese patients with type 2 diabetes: a prospective cohort study [Diabetes Distress and Care Registry at Tenri (DDCRT 10)

To assess the prospective association between baseline serum uric acid level and subsequent risk of development or progression in albuminuria. Longitudinal data were obtained from 2518 patients with type 2 diabetes in the development cohort and registered in a Japanese diabetes registry. To assess the independent correlations between baseline serum uric acid quartiles and either the development or progression of diabetic nephropathy for 2years, the Cox proportional hazards model was used and adjusted for potential confounders. The mean patient age, body mass index, and glycated hemoglobin (HbA1c) level were 66.1years, 24.6kg/m(2), and 7.5% (57.6mmol/mol), respectively. The baseline serum uric acid levels, with mean values of 3.6, 4.9, 5.8, and 7.3mg/dL from the first to fourth quartiles, were significantly associated with the urinary albumin/creatinine ratio at baseline (p<0.001). Baseline uric acid levels were not significantly associated with the development of nephropathy, but they were with the progression of nephropathy. The multivariable-adjusted hazards ratios for the progression from microalbuminuria to macroalbuminuria were 2.17 [95% confidence interval (CI) 1.15-4.08; p=0.016], 3.04 (95% CI 1.67-5.53; p<0.001), and 3.56 (95% CI 1.83-6.93; p<0.0011) for the first, third, and fourth quartiles of serum uric acid levels, respectively, as compared to that for the second quartile. We did not observe significant association between uric acid levels and change in estimated glomerular filtration rate. Low and high serum uric levels, independent of possible confounders, were associated with a subsequent risk of progression, not development, in albuminuria in type 2 diabetes patients. Therefore, serum uric acid levels may be useful for predicting the future risk of progression of microalbuminuria.

The first metatarsophalangeal joint in gout and asymptomatic hyperuricaemia

Background Gout is a painful arthritis associated with high serum urate levels (hyperuricaemia) and subsequent crystal deposition in joints. Although not all people with Asymptomatic Hyperuricaemia (AH) develop gout, crystal deposition and sub-clinical joint damage have been observed in this population. Gout most commonly affects the first metatarsophalangeal joint (1MTP). Existing theories suggest this may be related to the structure and functional role of the joint during gait, yet such characteristics of the 1MTP have not been investigated in people with gout or with AH. The objective of this study was to identify 1MTP characteristics in these people by comparing them with normouricaemic controls.