Uric acid levels predict survival in men with amyotrophic lateral sclerosis.
ABSTRACT: Elevated uric acid levels have recently been found to be associated with slower disease progression in Parkinson's disease, Huntington's disease, multiple system atrophy, and mild cognitive impairment. The aim of this study is to determine whether serum uric acid levels predict survival in amyotrophic lateral sclerosis (ALS). A total of 251 people with ALS enrolled in two multicenter clinical trials were included in our analysis. The main outcome measure was survival time, which was calculated as time to death, tracheostomy, or permanent assistive ventilation, with any event considered a survival endpoint. Cox proportional hazards models were used to estimate the hazard ratio (HR) of reaching a survival endpoint according to baseline uric acid levels after adjusting for markers of disease severity (FVC, total ALSFRS-R score, time since symptom onset, diagnostic delay, BMI, bulbar vs. spinal onset, age, and riluzole use). There was a dose-dependent survival advantage in men, but not women, with higher baseline uric acid levels (logrank test: p = 0.018 for men, p = 0.81 for women). There was a 39% reduction in risk of death during the study for men with each 1 mg/dl increase in uric acid levels (adjusted HR: 0.61, 95% CI 0.39-0.96, p = 0.03). This is the first study to demonstrate that serum uric acid is associated with prolonged survival in ALS, after adjusting for markers of disease severity. Similar to previous reports in Parkinson's disease, this association was seen in male subjects only.
Project description:INTRODUCTION:Urate has been identified as a predictor of amyotrophic lateral sclerosis (ALS) survival in some but not all studies. Here we leverage the recent expansion of the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database to study the association between urate levels and ALS survival. METHODS:Pooled data of 1,736 ALS participants from the PRO-ACT database were analyzed. Cox proportional hazards regression models were used to evaluate associations between urate levels at trial entry and survival. RESULTS:After adjustment for potential confounders (i.e., creatinine and body mass index), there was an 11% reduction in risk of reaching a survival endpoint during the study with each 1-mg/dL increase in uric acid levels (adjusted hazard ratio 0.89, 95% confidence interval 0.82-0.97, P < 0.01). DISCUSSION:Our pooled analysis provides further support for urate as a prognostic factor for survival in ALS and confirms the utility of the PRO-ACT database as a powerful resource for ALS epidemiological research. Muscle Nerve 57: 430-434, 2018.
Project description:The association between Parkinson's disease (PD) and uric acid levels has gained intensive interest in recent years. We applied meta-analysis to investigate serum uric acid levels in patients with PD in comparison with healthy controls.We searched three electronic databases and reference lists up to January 2013. Two collaborators reviewed all the articles and data disagreement was resolved through discussion. Six studies met the eligibility criteria and were included in the meta-analysis of uric acid levels in patients with PD in comparison with controls.1217 patients with PD and 1276 matched healthy controls.The meta-analysis results showed that patients with PD had lower levels of uric acid than healthy controls (summary standardised mean difference (SMD)=-0.52, 95% CI (-0.72 to -0.31)). Further gender subgroup analysis (summary SMD=-0.56, 95% CI (-0.72 to -0.41) for women; summary SMD=-0.62, 95% CI (-0.94 to -0.31) for men) indicated lower uric acid levels in patients with PD than healthy controls in women and men.It was found that patients with PD had lower serum levels of uric acid than healthy controls and this association was more significant in men than in women. More efforts are encouraged to explore the prognostic and therapeutic implications for PD of the present findings.
Project description:To pool data from completed amyotrophic lateral sclerosis (ALS) clinical trials and create an open-access resource that enables greater understanding of the phenotype and biology of ALS.Clinical trials data were pooled from 16 completed phase II/III ALS clinical trials and one observational study. Over 8 million de-identified longitudinally collected data points from over 8,600 individuals with ALS were standardized across trials and merged to create the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. This database includes demographics, family histories, and longitudinal clinical and laboratory data. Mixed effects models were used to describe the rate of disease progression measured by the Revised ALS Functional Rating Scale (ALSFRS-R) and vital capacity (VC). Cox regression models were used to describe survival data. Implementing Bonferroni correction, the critical p value for 15 different tests was p = 0.003.The ALSFRS-R rate of decline was 1.02 (±2.3) points per month and the VC rate of decline was 2.24% of predicted (±6.9) per month. Higher levels of uric acid at trial entry were predictive of a slower drop in ALSFRS-R (p = 0.01) and VC (p < 0.0001), and longer survival (p = 0.02). Higher levels of creatinine at baseline were predictive of a slower drop in ALSFRS-R (p = 0.01) and VC (p < 0.0001), and longer survival (p = 0.01). Finally, higher body mass index (BMI) at baseline was associated with longer survival (p < 0.0001).The PRO-ACT database is the largest publicly available repository of merged ALS clinical trials data. We report that baseline levels of creatinine and uric acid, as well as baseline BMI, are strong predictors of disease progression and survival.
Project description:Purpose:The purpose of this study was to investigate the relationship between high intraocular pressure (IOP) and uric acid. Methods:In a retrospective cross-sectional study, 19,147 participants were included in 2018. Serum uric acid (SUA) was cut to four groups as Q1 to Q4, according to the quartiles. The odds ratio (OR) and 95% confidence interval (CI) of different SUA levels were estimated by a binomial logistic regression model in men and women. A restrictive cubic spline method was used to estimate the dose-response relationship between uric acid and high IOP. Subgroup analysis was performed to find the gender-specific association between uric acid and high IOP. Results:In women, after adjusting for confounding factors, the Q3 and Q4 of SUA levels were significantly associated with the risk of high IOP. The OR with 95% CI for Q3 and Q4 were 1.77 (1.22, 2.57) and 1.51 (1.01, 2.26), respectively, Q1 as a reference. For men, SUA levels were not associated with the incidence of high IOP. Moreover, the spline analysis found an inverted U-shaped relationship between uric acid and high IOP in women (P = 0.0171). Conclusions:Elevated levels of SUAwere independently associated with an increased risk of high IOP in women, but not in men. In addition, uric acid had an inverse U-shaped nonlinear dose-response relationship with high IOP in women.
Project description:Hyperuricemia and gout are associated with an increased risk of cardiovascular disease (CVD). It is unknown whether treating hyperuricemia with xanthine oxidase inhibitors (XOIs), including allopurinol and febuxostat, modifies cardiovascular risks.We used US insurance claims data to conduct a cohort study among gout patients, comparing XOI initiators with non-users with hyperuricemia defined as serum uric acid level ?6.8 mg/dL. We calculated incidence rates of a composite nonfatal cardiovascular outcome that included myocardial infarction, coronary revascularization, stroke, and heart failure. Propensity score (PS)-matched Cox proportional hazards regression compared the risk of composite cardiovascular endpoint in XOI initiators vs those with untreated hyperuricemia, controlling for baseline confounders. In a subgroup of patients with uric acid levels available, PS-matched Cox regression further adjusted for baseline uric acid levels.There were 24,108 PS-matched pairs with a mean age of 51 years and 88% male. The incidence rate per 1000 person-years for composite CVD was 24.1 (95% confidence interval [CI] 22.6-26.0) in XOI initiators and 21.4 (95% CI, 19.8-23.2) in the untreated hyperuricemia group. The PS-matched hazard ratio for composite CVD was 1.16 (95% CI, 0.99-1.34) in XOI initiators vs those with untreated hyperuricemia. In subgroup analyses, the PS-matched hazard ratio for composite CVD adjusted for serum uric acid levels was 1.10 (95% CI, 0.74-1.64) among XOI initiators.Among patients with gout, initiation of XOI was not associated with an increased or decreased cardiovascular risk compared with those with untreated hyperuricemia. Subgroup analyses adjusting for baseline uric acid levels also showed no association between XOI and cardiovascular risk.
Project description:INTRODUCTION:Smoking status based solely on self-reporting is unreliable and might be inaccurate, particularly among women. This study investigated the association between urinary cotinine-verified smoking status and hyperuricemia in a nationwide Korean population. METHODS:This study included 5329 participants aged ?19 years with information on smoking status, urine cotinine levels and serum uric acid. We determined smoking status according to self-reports and urinary cotinine levels. Multivariate linear regression analysis was used to measure the association between smoking exposure and serum uric acid levels. The effects of smoking on hyperuricemia were evaluated by multivariate logistic regression analysis. RESULTS:Biochemically verified active and passive smokers comprised 22% (38.7% of men and 8.8% of women) and 12.3% (11.9% of men and 12.6% of women) of the study population, respectively. While reclassification rate of active smokers was 1.4% in men, 31.8% of cotinine-verified female active smokers were self-reported never smokers. Higher uric acid levels were observed with increased tobacco exposure among women (p-trend=0.007) but not among men. After adjusting for confounders, the risk of hyperuricemia increased with tobacco exposure only in women (p-trend=0.016). CONCLUSIONS:Cotinine-verified smoking status was associated with increased serum uric acid and hyperuricemia in a dose-response manner only in women. This study might provide evidence to support the importance of smoking cessation in women with gout and further studies are necessary to elucidate the underlying mechanism of the observed association.
Project description:Kidney disease is expected to become the fifth leading cause of premature death globally by 2040. Uric acid level is a risk factor for kidney disease. The current study aims to investigate the association between uric acid levels and kidney function in the Korean population. The data of 11,042 participants of the 2016-2017 Korea National Health and Nutrition Examination Survey were analysed. The estimated glomerular filtration rate was calculated using the modification of diet in renal disease formula for Koreans. For each sex, uric acid levels were divided into five subsequent categories of increasing levels (Q1, Q2, Q3, Q4, and hyperuricemia). The association between uric acid level and kidney function was investigated using multiple logistic regression. The results showed that the higher the uric acid levels, the greater the odds of reduced kidney function in both sexes. In men, the adjusted odds ratios (95% confidence intervals) for reduced eGFR comparing the hyperuricemia group to the lowest serum uric acid quartile was 5.55 (3.27-9.44), and in women, the odds ratios (95% confidence intervals) was 7.52 (4.39-12.87). Normal weight or underweight in men and overweight in women, as well as diabetes mellitus, hypertension, and physical inactivity were highly associated with reduced kidney function. Our study revealed a dose-response relationship between uric acid levels and kidney function. Therefore, high uric acid level should be considered as a factor that is potentially related to kidney dysfunction in the Korean population.
Project description:Lupus nephritis (LN) is a major complication of systemic lupus erythematosus. Early intervention in lupus nephritis improves prognosis. There is an association between hyperuricemia and lupus nephritis; nevertheless, the sex-specific role of uric acid in lupus nephritis remains unclear. We retrospectively analyzed 578 patients diagnosed with LN by renal biopsy. We determine the relationship of serum uric acid to progression of LN using Kaplan-Meier survival analyses and Cox proportional hazards models. The primary end point was LN progression defined as the initiation of dialysis or kidney transplantation. Men had higher mean serum uric acid levels than did women. Every 1 mg/dL increase in baseline uric acid level increased the risk of LN progression by 15.1%. The serum uric acid level was an independent risk factor for LN progression in women (hazard ratio [HR], 1.158; confidence interval [CI], 1.018-1.317; p = 0.028) but not in men (HR, 1.499; CI, 0.964-2.331; p = 0.072). Sensitivity analysis involving serum uric acid terciles generated consistent and robust results. Serum uric acid level was an independent risk factor for LN progression in women but not in men.
Project description:<h4>Objective</h4>Experimental and observational studies suggest a role for uric acid in non-alcoholic fatty liver disease (NAFLD). We examined the association between serum uric acid levels and NAFLD in a large population-based study from the United States.<h4>Materials/methods</h4>A cross-sectional analysis of 10,732 nondiabetic adults who participated in the National Health and Nutrition Examination Survey 1988-1994. Sex specific uric acid quartiles were defined: ?5.2, 5.3-6.0, 6.1-6.9, and >6.9mg/dL for men and ?3.7, 3.8-4.5, 4.6-5.3, and >5.3mg/dL for women. NAFLD presence and severity were defined by ultrasonographic detection of steatosis in the absence of other liver diseases. We modeled the probability that more severe NAFLD would be associated with the highest quartiles of uric acid.<h4>Results</h4>Compared to the 1st quartile, the odds ratio for NAFLD was 1.79 (95% C.I. 1.49-2.15, p<0.001) and 3.14 (95% C.I. 2.63-3.75, p<0.001) for the 3rd and 4th quartiles, respectively. After adjusting for demographics, hypertension, waist circumference, triglycerides, high-density lipoprotein-cholesterol, homeostasis model assessment-estimated insulin resistance, estimated glomerular filtration rate, and aspartate aminotransferase, uric acid (4th quartile) was significantly associated with NAFLD (odds ratio 1.43; 95% C.I. 1.16-1.76, p<0.001). Positive parameter estimates suggest increasing uric acid is associated with greater severity of NAFLD.<h4>Conclusions</h4>Elevated uric acid level is independently associated with ultrasound-diagnosed NAFLD in a nationally representative sample of United States nondiabetic adults. Increasing uric acid is associated with increasing severity of NAFLD on ultrasonography. These findings warrant further studies on the role of uric acid in NAFLD.
Project description:Individuals with Parkinson's disease (PD) have lower uric acid levels than those without PD, and the CC genotype and C minor allele of a single nucleotide polymorphism (SNP), rs1014290 of SLC2A9, are associated with lower uric acid levels. We investigated the association of rs1014290 with uric acid metabolism in a cohort of PD cases (220) and controls (110) in a Han Chinese population. Uric acid levels were determined and rs1014290 was assayed using a mutation-sensitive on/off switch technology. PD uric acid levels (291.65 ± 76.29??mol/L) were significantly lower than the controls (325.73 ± 74.23??mol/L, P < 0.001, t-test). Individuals with rs1014290 TT and CT genotypes had higher uric acid levels, and those with the CC genotype had the lowest uric acid levels among both control and PD cases. The CC genotype and the C minor allele were statistically more frequent in the PD group compared to the control group. Those with the CC genotype had a statistically significant higher risk of PD than those with the TT or TC genotype (odds ratio [OR] = 2.249, 95% confidence interval [CI]: 1.129-4.480, and P = 0.021). Thus, SLC2A9 rs1014290 is related to lower uric acid levels in PD patients and can be a risk factor for PD in the Han population.