Background: Although the clinical implication of hyperuricemia in chronic kidney disease has been an issue of active debate, recent data suggested a causative role of uric acid (UA) in the development of renal disease. Afferent arteriopathy, an induction of oxidative stress and an activation of local inflammation, have been regarded as the mechanisms of UA-induced renal disease, which contribute to glomerular hypertrophy and interstitial fibrosis via endothelial dysfunction. However, there have been rare studies on the direct effect of UA on phenotype transition of renal cells such as epithelial-to-mesenchymal transition (EMT) or endothelial-to-mesenchymal transition (EndoMT). Summary: We have reported that UA-induced EMT of cultured renal tubular cells, which was blocked by the organic anion transport inhibitor, probenecid. UA increased the expression of snail and slug, the transcriptional repressors of E-cadherin, which resulted in a downregulation of E-cadherin production. UA also increased the degradation of E-cadherin via ubiquitination. UA also induced EndoMT with an increase in ROS generation and glycocalyx shedding of cultured vascular endothelial cells. Treatment with antioxidants ameliorated UA-induced EndoMT. In the kidney of hyperuricemic rats, there was an evidence of EMT before the development of significant tubulointerstitial fibrosis, as shown by decreased E-cadherin expression and an increased α-smooth muscle actin (α-SMA) in renal tubular cells. Allopurinol significantly inhibited UA-induced EMT with an amelioration of renal fibrosis. In addition, endothelial staining in peritubular capillaries (PTC) was substantially decreased with de-novo expression of α-SMA in endothelial cells of PTC. Key Messages: UA per se induced a phenotypic transition of epithelial and endothelial cells via an induction of oxidative stress and glycocalyx shedding, which could be one of the mechanisms of UA-induced kidney disease.