Uric acid is independent and inversely associated to glomerular filtration rate in young adult Brazilian individuals.

BACKGROUND AND AIMS: Uric acid, the end-product of human purine metabolism, is associated with hypertension, diabetes and obesity. It has also been independently associated with the onset of chronic kidney disease in several populations. In this study, the association between serum uric acid (SUA) level and estimated glomerular filtration rate (eGFR) was investigated in healthy individuals belonging to two Brazilian birth cohorts. METHODS AND RESULTS: Data from 3541 to 3482 individuals, aged 30 and 22-years old, respectively, was included. eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on creatinine measurement. Regression analyses were sex-stratified due to interaction between SUA and sex (p < 0.001) and adjusted for perinatal, cardiometabolic and behavioral variables. We observed an inverse association between eGFR and SUA even after adjustment. In the highest tertile (3rd) of SUA, the eGFR coefficients at 30-years were-0.21 (95%CI -0.24;-0.18) for men and -0.20 (95%CI -0.23; -0.17) for women; at 22-years, were -0.09 (95%CI -0.12;-0.05) for men and -0.13 (95%CI -0.15; -0.10) for women. Higher differences among exponential means (95% CI) of eGFR between the 1st and the 3rd tertile of SUA were seen in older participants, being more pronounced in men. At 22-years, the highest difference was found in women. CONCLUSIONS: In young healthy individuals from a low-middle income country, SUA level was inversely associated with eGFR. Gender-related differences in eGFR according tertiles of SUA were higher in men at 30-years and in women at 22-years.

Metabolic Profiling of Adiponectin Levels in Adults: Mendelian Randomization Analysis.

BACKGROUND: Adiponectin, a circulating adipocyte-derived protein, has insulin-sensitizing, anti-inflammatory, antiatherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown. Our aims were to define the metabolic profile associated with higher blood adiponectin concentration and investigate whether variation in adiponectin concentration affects the systemic metabolic profile. METHODS AND RESULTS: We applied multivariable regression in ≤5909 adults and Mendelian randomization (using cis-acting genetic variants in the vicinity of the adiponectin gene as instrumental variables) for analyzing the causal effect of adiponectin in the metabolic profile of ≤37 545 adults. Participants were largely European from 6 longitudinal studies and 1 genome-wide association consortium. In the multivariable regression analyses, higher circulating adiponectin was associated with higher high-density lipoprotein lipids and lower very-low-density lipoprotein lipids, glucose levels, branched-chain amino acids, and inflammatory markers. However, these findings were not supported by Mendelian randomization analyses for most metabolites. Findings were consistent between sexes and after excluding high-risk groups (defined by age and occurrence of previous cardiovascular event) and 1 study with admixed population. CONCLUSIONS: Our findings indicate that blood adiponectin concentration is more likely to be an epiphenomenon in the context of metabolic disease than a key determinant.