Lung function decline is associated with serum uric acid in Korean health screening individuals.
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ABSTRACT:
SUBMITTER: Ahn KM
PROVIDER: S-EPMC8119944 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:While elevated serum uric acid level (SUA) is a recognized risk factor for chronic kidney disease, it remains unclear whether change in SUA is independently associated with change in estimated glomerular filtration rate (eGFR) over time. Accordingly, we examined the longitudinal associations between change in SUA and change in eGFR over 5 years in a general Japanese population. METHODS:This was a large, single-center, retrospective 5-year cohort study at St. Luke's International Hospital, Tokyo, Japan, between 2004 and 2009. We included 13,070 subjects (30-85 years) in our analyses whose data were available between 2004 and 2009. Of those, we excluded 492 subjects with eGFR <60 mL/min/1.73 m2 at baseline. In addition to examining the entire cohort (n = 12,578), we stratified our analyses by baseline eGFR groups: 60-90, 90-120, and ?120 mL/min/1.73 m2. Linear and logistic regressions models were applied to examine the relationships between baseline and change in SUA, change in eGFR, and rapid eGFR decline (defined as the highest quartile of change in eGFR), adjusted for age, gender, body mass index, abdominal circumference, hypertension, dyslipidemia, and diabetes mellitus. RESULTS:After multivariable adjustments including baseline eGFR, 1 mg/dL increase in baseline SUA was associated with greater odds of developing rapid eGFR decline (OR 1.27, 95% CI 1.17-1.38), and 1 mg/dL increase in SUA over 5 years was associated with 3.77-fold greater odds of rapid eGFR decline (OR 3.77, 95% CI 3.35-4.26). CONCLUSIONS:Elevated baseline SUA and increasing SUA over time were independent risk factors for rapid eGFR decline over 5 years.
| S-EPMC5894505 | biostudies-literature
Project description:BackgroundA limited number of epidemiological studies have investigated the association between serum uric acid and pulmonary function in the general population. However, the results have been inconclusive.ObjectivesThis study was performed to investigate the association between serum uric acid and spirometric pulmonary function in general population.MethodsAmong the 8,150 participants who participated in the 2016 Korea National Health and Nutrition Examination Survey, 2,901 participants were analyzed in this study. Subjects were divided into four groups according to forced vital capacity (FVC)% predicted or forced expiratory volume in 1 second (FEV1) % predicted quartiles. Participants in the lowest quartile of FVC % predicted and FEV1% predicted were compared to those in the remaining quartiles according to age, education level, household income, smoking status, alcohol consumption, aerobic exercise, obesity, hypertension, diabetes, renal impairment, serum uric acid, and hyperuricemia. Multivariable logistic regression analyses were used to calculate the odds ratio (OR) of hyperuricemia for participants in the lowest quartile of FVC% and FEV1 predicted, with above covariates.ResultsIn women, hyperuricemia was associated with lowest quartile of FVC% predicted (OR 1.71, 95% CI 1.06-2.75, p = 0.027) and FEV1 predicted (OR 1.70, 95% CI 1.06-2.74, p = 0.028) respectively, serving as above confounding variables. In men, hyperuricemia (OR 1.54, 95% CI 1.07-2.22, p = 0.021) was associated with the lowest quartile of FEV1% predicted, not FVC% predicted. According to median age, in women, age ≥ 56 years old with hyperuricemia was associated with lowest quartile of FVC% predicted (OR 1.85, 95% CI 1.04-3.28, p = 0.037) and FEV1% predicted (OR 1.99, 95% CI 1.11-3.75, p = 0.021), respectively. In men, age ≥ 56 years old with hyperuricemia was associated with lowest quartile of FEV1% predicted (OR 1.75, 95% CI 1.05-2.94, p = 0.033), not FCV% predicted.ConclusionsHyperuricemia was associated with lowest quartile of FEV1% or FVC% predicted in Korean general population. This correlation between hyperuricemia and low pulmonary function was more pronounced in women and older age.
| S-EPMC7580900 | biostudies-literature
Project description:Increased serum uric acid (SUA) levels cause gout and are associated with multiple diseases, including chronic kidney disease. Previous genome-wide association studies (GWAS) have identified more than 180 loci that contribute to SUA levels. Here, we investigated genetic determinants of SUA level in the Korean population. We conducted a GWAS for SUA in 6,881 Korean individuals, calculated polygenic risk scores (PRSs) for common variants, and validated the association of low-frequency variants and PRS with SUA levels in 3,194 individuals. We identified two low-frequency and six common independent variants associated with SUA. Despite the overall similar effect sizes of variants in Korean and European populations, the proportion of variance for SUA levels explained by the variants was greater in the Korean population. A rare, nonsense variant SLC22A12 p.W258X showed the most significant association with reduced SUA levels, and PRSs of common variants associated with SUA levels were significant in multiple Korean cohorts. Interestingly, an East Asian-specific missense variant (rs671) in ALDH2 displayed a significant association on chromosome 12 with the SUA level. Further genetic epidemiological studies on SUA are needed in ethnically diverse cohorts to investigate rare or low-frequency variants and determine the influence of genetic and environmental factors on SUA.
| S-EPMC7280503 | biostudies-literature
Project description:An elevated serum urate concentration is associated with kidney damage. Men's uric acid levels are usually higher than women's. However, postmenopausal women have a higher risk of gout than men, and comorbidities are also higher than in men. This study examined the sex differences in the relationship between hyperuricemia and renal progression in early chronic kidney disease (CKD) and non-CKD, and further examined the incidence of CKD in non-CKD populations among patients over 50 years of age. We analyzed 1856 women and 1852 men participating in the epidemiology and risk factors surveillance of the CKD database. Women showed a significantly higher risk of renal progression and CKD than men within the hyperuricemia group. After adjusting covariates, women, but not men resulted in an hazard ratio (HR) for developing renal progression (HR = 1.12; 95% CI 1.01-1.24 in women and HR = 1.03; 95% CI 0.93-1.13 in men) and CKD (HR = 1.11; 95% CI 1.01-1.22 in women and HR = 0.95; 95% CI 0.85-1.05 in men) for each 1 mg/dL increase in serum urate levels. The association between serum urate levels and renal progression was stronger in women. Given the prevalence and impact of kidney disease, factors that impede optimal renal function management in women and men must be identified to provide tailored treatment recommendations.
| S-EPMC8156506 | biostudies-literature
Project description:The oxidant/antioxidant imbalance plays a pivotal role in the lung. Uric acid (UA), an endogenous antioxidant, is highly present in lung tissue, however, its impact on lung function under pathophysiological conditions remains unknown. In this work, pharmacological and genetic inhibition of UA metabolism in experimental mouse models of acute and chronic obstructive pulmonary disease (COPD) revealed that increased plasma UA levels improved emphysematous phenotype and lung dysfunction in accordance with reduced oxidative stress specifically in female but not in male mice, despite no impact of plasma UA induction on the pulmonary phenotypes in nondiseased mice. In vitro experiments determined that UA significantly suppressed hydrogen peroxide (H2O2)-induced oxidative stress in female donor-derived primary human bronchial epithelial (NHBE) cells in the absence of estrogen, implying that the benefit of UA is limited to the female airway in postmenopausal conditions. Consistently, our clinical observational analyses confirmed that higher blood UA levels, as well as the SLC2A9/GLUT9 rs11722228 T/T genotype, were associated with higher lung function in elderly human females. Together, our findings provide the first unique evidence that higher blood UA is a protective factor against the pathological decline of lung function in female mice, and possibly against aging-associated physiological decline in human females.
| S-EPMC7278835 | biostudies-literature
Project description:OBJECTIVES:Despite the growing pieces of evidence linking hyperuricemia with metabolic syndrome and cardiovascular disease, the relationship between dyslipidemia and serum uric acid has not yet been established. This study aimed to investigate the association between individual components of dyslipidemia and serum uric acid by using the nationally representative Korea National Health and Nutrition Examination Survey 2016-2017. METHODS:A total of 8,722 participants (age ? 19 years) without missing values were analyzed for this study. Serum uric acid levels according to the presence of individual dyslipidemia components were calculated using multivariable-adjusted general linear models (GLM). Odds ratios of individual dyslipidemia components to hyperuricemia were calculated using unadjusted and multivariable-adjusted logistic regression analysis. RESULTS:A total of 1,061 participants were identified as having hyperuricemia, with a prevalence of 12.2%. Multivariable-adjusted GLM demonstrated a significant trend between individual dyslipidemia components and serum uric acid levels (P < 0.05). A positive association between the numbers of dyslipidemia components and the increments of serum uric acid levels was also observed (P < 0.001). In multivariable-adjusted logistic regression analysis, odds ratios (OR) and 95% confidence interval (CI) of all dyslipidemia components to hyperuricemia were shown to be statistically significant (P < 0.05). When further adjusted for the combined components themselves, each 10 mg/dL increments of total cholesterol (OR 1.053; 95% CI 1.028-1.079), triglycerides (OR 1.017; 95% CI 1.009-1.026) and HDL-C (OR 0.804; 95% CI 0.729-0.887), retained significant correlation with hyperuricemia. CONCLUSION:Our study demonstrated that the dyslipidemia components of serum total cholesterol, triglycerides and LDL-C levels are positively associated with serum uric acid levels, whereas serum HDL-C levels are inversely related. Further complementary studies regarding other lipid parameters are needed to confirm the accurate association between dyslipidemia and serum uric acid levels.
| S-EPMC7021293 | biostudies-literature
Project description:ObjectiveSerum uric acid is the end-product of purine metabolism and at high levels is a risk factor for several human diseases including gout and cardiovascular disease. Heritability estimates range from 0.32 to 0.63. Genome-wide association studies (GWAS) provide an unbiased approach to identify loci influencing serum uric acid. Here, we performed the first GWAS for serum uric acid in continental Africans, with replication in African Americans.MethodsAfricans (n?=?4126) and African Americans (n?=?5007) were genotyped on high-density GWAS arrays. Efficient mixed model association, a variance component approach, was used to perform association testing for a total of ~?18 million autosomal genotyped and imputed variants. CAVIARBF was used to fine map significant regions.ResultsWe identified two genome-wide significant loci: 4p16.1 (SLC2A9) and 11q13.1 (SLC22A12). At SLC2A9, the most strongly associated SNP was rs7683856 (P?=?1.60?×?10-44). Conditional analysis revealed a second signal indexed by rs6838021 (P?=?5.75?×?10-17). Gene expression and regulatory motif data prioritized a single-candidate causal variant for each signal. At SLC22A12, the most strongly associated SNP was rs147647315 (P?=?6.65?×?10-25). Conditional analysis and functional annotation prioritized the missense variant rs147647315 (R (Arg) > H (His)) as the sole causal variant. Functional annotation of these three signals implicated processes in skeletal muscle, subcutaneous adipose tissue and the kidneys, respectively.ConclusionsThis first GWAS of serum uric acid in continental Africans identified three associations at two loci, SLC2A9 and SLC22A12. The combination of weak linkage disequilibrium in Africans and functional annotation led to the identification of candidate causal SNPs for all three signals. Each candidate causal variant implicated a different cell type. Collectively, the three associations accounted for 4.3% of the variance of serum uric acid.
| S-EPMC7015846 | biostudies-literature
Project description:AbstractGiven that factors affecting renal function remain unknown, this study aimed to identify key predictors of estimated glomerular filtration rate (eGFR) deterioration, which is a representative of renal function decline in older adults with type 2 diabetes (T2DM). In an exploratory prospective observational study, we enrolled 268 Japanese people with T2DM aged ≥20 years who were followed up at Shinshu University Hospital. Among those, 112 eligible individuals aged ≥65 years were included in the present study. Factors associated with 3-year changes in eGFR (ΔeGFR) and eGFR deterioration (ΔeGFR < 0) were identified using bivariate and multivariable analyses. Regarding baseline values of the subjects, the mean age was 73.5 years, mean blood pressure was 131/74 mm Hg, mean hemoglobin A1c was 7.1%, mean eGFR was 62.0 mL/min/1.73 m2, mean urinary albumin excretion was 222.6 mg/gCre, and mean serum uric acid (UA) was 5.5 mg/mL. In bivariate analysis, the 3-year change in UA (ΔUA) levels was significantly correlated with ΔeGFR (r = -0.491, P < .001), but the baseline UA was not (r = 0.073, P = .444). Multiple linear regression analysis revealed that ΔUA was a significant negative predictor of ΔeGFR in the model that included sex, age, body mass index, serum albumin, and ΔUA as explanatory variables. Moreover, multiple logistic regression analysis demonstrated that ΔUA had a positive association with ΔeGFR <0 (odds ratio 2.374; 95% confidence interval 1.294-4.357). Thus, future renal function decline can be predicted by ΔUA but not by baseline UA in older adults with T2DM. Further research is needed to determine whether lowering the serum UA level can prevent eGFR decline.
| S-EPMC8500559 | biostudies-literature
Project description:High normal concentrations of serum uric acid (UA) are associated with mild cognitive dysfunction and increased cerebral ischemia as indexed by white matter hyperintensity volumes. We hypothesized that individual differences in white matter hyperintensities mediate the association between UA and mild cognitive dysfunction.One hundred eighty community-dwelling adults aged 20 to 96 years completed neuropsychological testing, laboratory blood studies, and a brain MRI scan.Serum UA was associated (P<0.05) with greater white matter hyperintensities and poorer working memory, processing speed, fluency, and verbal memory. Associations remained after controlling for age, sex, race, education, hypertension, diabetes, alcohol abuse, smoking, and body mass. Adding a term for white matter hyperintensity attenuated these associations such that UA no longer predicted cognitive performance.Severity of cerebral ischemia might mediate the association between UA and cognitive dysfunction. Even mild elevations in UA appear to contribute to structural and functional brain changes.
| S-EPMC4876431 | biostudies-literature
Project description:Serum uric acid (SUA) is an abundant natural antioxidant capable of reducing cellular oxidation, a major cause of neurodegenerative disease. In line with this, SUA levels are lower in Alzheimer's disease; however, the association between SUA and cognition remains unclear. Results from studies examining the effects of SUA on cognition may be difficult to interpret in the context of normal versus pathological aging. This study examined sex-specific associations of baseline SUA with cognition during aging. Data from dementia-free participants initially aged 26-99 (N?=?1,451) recruited for the Baltimore Longitudinal Study of Aging (BLSA), were used in the current analyses. SUA was assessed using blood samples collected during research visits. Cognition was measured using five composite scores (verbal memory, attention, executive function, language, and visuospatial ability). At the first study visit, compared with women, men were older, more likely to be White, had more years of education, higher baseline SUA levels, and higher cardiovascular risk scores. Higher baseline SUA was associated with attenuated declines in attention (?=?0.006; p?=?0.03) and visuospatial abilities (?=?0.007; p?=?0.01) in men. There was a trend to suggest higher baseline SUA in men was associated with attenuated declines in language, but this finding did not reach statistical significance (p?=?0.09). There were no significant findings with SUA and cognition in women. In this sample of cognitively healthy, community-dwelling adults, we found that higher SUA levels at baseline were associated with attenuated declines in attention and visuospatial abilities in men. SUA was not associated with cognition or change in cognition over time in women.
| S-EPMC6112110 | biostudies-literature