Elevated serum uric acid Phenobarbital concentrations are correlated with various metabolic profiles and healthy lifestyles, such as moderate-to-heavy alcohol consumption and metabolic syndrome components. Consequently, the potential influences of these factors should be considered when interpreting the results. Our sensitivity analysis indicated that a positive association persisted and remained significant even when analyses were limited to studies that adjusted for metabolic syndrome or alcohol intake. The existing evidence from cohort studies supports an independent, exacerbating effect of serum uric acid on CKD. Recent experimental metabolic studies consistently indicate that uric acid may have a causative role in the PHA-543613 development of CKD. Although serum uric acid is believed to possess antioxidant activity in the extracellular environment, uric acid appears to exert various deleterious effects once it enters cells. Uric acid enters vascular smooth muscle cells and activates intracellular protein kinases and nuclear transcription factors, resulting in a proliferative phenotype with the production of cyclooxygenase-2 and monocyte chemoattractant protein-1 and the activation of the rennin-angiotensin system. Increased uric acid inhibits the proliferation and migration of endothelial cells and the secretion of nitric oxide, contributing to endothelial dysfunction. Additionally, uric acid can promote proinflammatory mechanisms and induce NADPH oxidase stimulation, thereby promoting mitochondrial dysfunction. In animal studies, hyperuricemia results in the development of glomerular hypertension in association with elevated renal vascular resistance and impaired peritubular circulation. Uric acid can also induce an epithelial-to-mesenchymal transition in renal tubular cells, which might serve as one of the earliest components of renal fibrosis. In addition to the direct role of uric acid in CKD,it is not implausible that uric acid plays a detrimental role through established risk factors for CKD, such as blood pressure. Although the blood pressure or hypertension status was adjusted in the analyses of the association between uric acid and CKD in most studies, only one study evaluated the impacts of blood pressure on this association by dividing participants into two groups according to complicated with hypertension or not.