Changes In Urate Levels Research Articles

Prediagnostic Amino Acid Metabolites and Risk of Gout, Accounting for Serum Urate: Prospective Cohort Study and Mendelian Randomization.

Our objective was to prospectively investigate prediagnostic population-based metabolome for risk of hospitalized gout (ie, most accurate, severe, and costly cases), accounting for serum urate. We conducted prediagnostic metabolome-wide analyses among 249,677 UK Biobank participants with nuclear magnetic resonance metabolomic profiling (N = 168 metabolites, including eight amino acids) from baseline blood samples (2006-2010) without a history of gout. We calculated multivariable hazard ratios (HRs) for hospitalized incident gout, before and after adjusting for serum urate levels; we included patients with nonhospitalized incident gout in a sensitivity analysis. Potential causal effects were evaluated with two-sample Mendelian randomization. Correcting for multiple testing, 107 metabolites were associated with incidence of hospitalized gout (n = 2,735) before urate adjustment, including glycine and glutamine (glutamine HR 0.64, 95% confidence interval [CI] 0.54-0.75, P = 8.3 × 10-8; glycine HR 0.69, 95% CI 0.61-0.78, P = 3.3 × 10-9 between extreme quintiles), and glycoprotein acetyls (HR 2.48, 95% CI 2.15-2.87, P = 1.96 × 10-34). Associations remained significant and directionally consistent following urate adjustment (HR 0.83, 95% CI 0.70-0.98; HR 0.86, 95% CI 0.76-0.98; HR 1.41, 95% CI 1.21-1.63 between extreme quintiles), respectively; corresponding HRs per SD were 0.91 (95% CI 0.86-0.97), 0.94 (95% CI 0.91-0.98), and 1.10 (95% CI 1.06-1.14). Findings persisted when including patients with nonhospitalized incident gout. Mendelian randomization corroborated their potential causal role on hyperuricemia or gout risk; with change in urate levels of -0.05 mg/dL (95% CI -0.08 to -0.01) and -0.12 mg/dL (95% CI -0.22 to -0.03) per SD of glycine and glutamine, respectively, and odds ratios of 0.94 (95% CI 0.88-1.00) and 0.81 (95% CI 0.67-0.97) for gout. These prospective findings with causal implications could lead to biomarker-based risk prediction and potential supplementation-based interventions with glycine or glutamine.

Urate in fingernail represents the deposition of urate burden in gout patients

Urate in the fingernails of gout patients and healthy volunteers was successfully detected by high-performance liquid chromatography (HPLC) with ultraviolet (UV) in our previous research. This study aimed to further investigate whether nail urate could be a proxy for the burden of monosodium urate (MSU) crystals deposits in gout. To this end, we conducted a study in two parts. Firstly, we successfully detected urate in the nail by HPLC–UV and evaluated nail urate concentrations in control subjects and patients with gout. As expected, we found that levels of nail urate were significantly higher in patients with gout than in healthy controls, and the nail urate level was significantly correlated with the volume of MSU crystals deposits measured by dual-energy CT (DECT). Secondly, we found that nail urate can reflect changes in urate levels in the body during urate lowering therapy through a 3-month follow-up study. Our results provide the possibility of quantification of urate in human fingernails as a non-invasive alternative for assessing MSU crystals deposits in gout.

Influence of androgen deprivation therapy on serum urate levels in patients with prostate cancer: A retrospective observational study.

ObjectivesAlthough estrogenic modulation of serum urate levels is well-known, the androgenic effect on urate homeostasis remains controversial. We investigated the effect of androgen deprivation therapy (ADT) on serum urate levels.MethodsWe retrospectively enrolled a total of 489 prostate cancer patients with available serum urate levels at baseline and 3 and 6 months after ADT (n = 150) or prostate surgery (n = 339). We extracted the demographic, clinical, and laboratory data from a data warehouse and compared the changes in urate levels between the two treatment groups and between the different ADT regimens (with versus without luteinizing hormone-releasing hormone (LHRH) agonists) using generalized estimating equation (GEE).ResultsThe baseline urate levels and the proportion of hyperuricemic subjects were comparable between the two groups. After 6 months, the urate levels were significantly decreased (by −0.66 mg/dL, 95% confidence interval (CI) [-0.81 to -0.51]) in the ADT group, whereas they did not significantly change in the surgery group in the univariate GEE analysis. The ADT group (4.7% from 18.0% at baseline) had a significantly lower proportion of hyperuricemic patients than surgery group (16.5% from 15.9% at baseline) at 6-month (p < 0.001). Regardless of whether LHRH agonists were used, the serial urate levels were lowered by the ADT. Temporal changes in the urate levels were significantly associated with the treatment group, baseline hyperuricemia, and poor functional or advanced cancer status. The ADT-related serum urate level reduction also remained significant in the multivariate GEE analysis (regression coefficient = −0.43 [−0.67 to −0.19] after 3 months and −0.37 [−0.64 to −0.10] after 6 months). Moreover, propensity-score-matched analyses yielded the same results.ConclusionsOur results showed that longitudinal serum urate levels were significantly reduced in men receiving ADT. This finding suggests that androgen could have an independent role in urate homeostasis.

The practical management of gout

Gout management requires a comprehensive strategy that considers both acute and chronic aspects of the disease. Acute gout flares should be treated with anti-inflammatory agents as rapidly as possible. The underlying hyperuricemia may be treated with urate-lowering agents initiated at a time appropriate for the individual patient. Successful urate lowering ultimately prevents flares and disease progression and should be started immediately in patients with advanced or tophaceous disease. When urate-lowering therapy is initiated, anti-inflammatory prophylaxis should be used to reduce the risk of flares induced by abrupt changes in urate levels. Regular monitoring of serum urate can ensure therapeutic dosing of urate-lowering agents to achieve levels below 6 mg/dL, which are associated with a reduction in flares and tophi.

METABOLIC EFFECTS OF THE STEROID ANTIBIOTIC FUSIDIC ACID.

OBJECTIVE: We aim to further evaluate survival differences and disease progression based on urate levels in a larger cohort of ALS patients. BACKGROUND: Low blood levels of urate (uric acid) have been demonstrated in patients with ALS. A dose-dependent survival advantage in men with higher baseline urate levels has also been shown, while no advantage was observed in women. DESIGN/METHODS: Pooled data of 1767 subjects with ALS (1,093 men, 674 women) from the PRO-ACT database were available for analysis. Random slopes and Cox proportional hazards regression models, adjusted for baseline predictors of disease severity, were used to evaluate associations between urate levels and ALSFRS-R decline and survival, respectively. RESULTS: Mean baseline urate levels differed significantly by gender (p&lt;0.001) and were significantly lower in women than men (4.2mg/dL and 5.4mg/dL respectively, difference in means -1.2). The change in urate levels over time did not differ significantly by gender (p=0.34). Baseline urate levels were significantly associated with weight (p&lt;0.0001) and creatinine (p&lt;0.0001). Multivariate analysis controlling for predictors of disease severity as well as urate*gender interaction, creatinine, and weight demonstrated that higher levels of urate at baseline were associated with slower ALSFRS-R decline over 1 year (p=0.01, difference = -0.07 decline in ALSFRS-R scores per month for each unit increase in urate levels). In multivariate analysis, the risk of dying of ALS over 1 year decreased by 11[percnt] (HR 0.89, 95[percnt] CI (0.81,0.98), p=0.01) for each unit (mg/dL) increase in baseline urate. When baseline weight was included as a co-variate, however, the survival models were no longer statistically significant. CONCLUSION: Our pooled analysis provides further support to urate levels as a prognostic factor in ALS and confirms the utility of the PRO-ACT database as a powerful resource for ALS epidemiological research. <b>Disclosure:</b> Dr. Nicholson has nothing to disclose. Dr. Paganoni has nothing to disclose. Dr. Shui has nothing to disclose. Dr. Schoenfeld has received personal compensation for activities with Seno, Galena Biopharma, Alexion Pharmaceuticals, Edison Pharmaceuticals, Anika Therapeutics, Hemispherix Biopharma, ZS Pharma, Inc., Aptalis, Mylan, Biogen Idec, Spinal, Polymedico, Inc Dr. Sherman has nothing to disclose. Dr. Berry has received personal compensation for activities with Oakstone Publishing as a speaker. Dr. Berry has received research support from the Muscular Dystrophy Association and ALS Therapy Alliance. Dr. Cudkowicz has received personal compensation for activities with GlaxoSmithKline, Biogen Idec, Teva Neuroscience, and Cytokinetics. Dr. Cudkowicz has received personal compensation in an editorial capacity for JAMA Neurology. Dr. Atassi has received personal compensation for activities with Biogen Idec as a consultant.