New Insights into Uric Acid Effects on the Progression and Prognosis of Chronic Kidney Disease

Figures & data

Table 1. Major pathophysiological mechanisms of uric acid-induced damage.

1.	Endothelial dysfunction through impaired NO production and release
2.	Increased oxidative stress mainly through xanthine oxidase (LDL oxidation and lipid peroxidation)
3.	Platelet activation (platelet aggregation and thrombosis)
4.	Vascular smooth muscle cells proliferation (COX-2, TXA2, PDGF)
5.	Proinflammatory activity (MCP-1, IL-1β, IL-6, TNF-α)

Note: NO, nitric oxide; LDL, low-density lipoprotein; COX-2, cyclooxygenase-2; TXA₂, thromboxane A₂; PDGF, platelet-derived growth factor; MCP-1, monocyte chemoattractant factor-1; IL, interleukin; TNF-α, tumor necrosis factor-α.

Figure 1. Pathways by which uric acid induces proliferative and inflammatory mechanisms. Uric acid enters vascular smooth muscle cells through specific OAT and activates intracellular MAP kinases, p38 and Erk 1/2, and nuclear transcription factors (NF-κB and AP-1), leading these cells to acquire a proliferative and inflammatory phenotype. Thus, vascular smooth muscle cells, through increased expression of COX-2 and TXA₂, produce cytokines, growth factors (PDGF), and proinflammatory molecules (MCP-1).

Note: OAT, organic anion transporter; MAP, mitogen-activated protein; NF-κB, nuclear factor kappa B; AP-1, activator protein-1; COX-2, cyclooxygenase-2; TXA₂, thromboxane; PDGF, platelet-derived growth factor; MCP-1, monocyte chemoattractant protein-1.