Uric Acid and Oxidative Stress-Relationship with Cardiovascular, Metabolic, and Renal Impairment

Abstract

Background: The connection between uric acid (UA) and renal impairment is well known due to the urate capacity to precipitate within the tubules or extra-renal system. Emerging studies allege a new hypothesis concerning UA and renal impairment involving a pro-inflammatory status, endothelial dysfunction, and excessive activation of renin-angiotensin-aldosterone system (RAAS). Additionally, hyperuricemia associated with oxidative stress is incriminated in DNA damage, oxidations, inflammatory cytokine production, and even cell apoptosis. There is also increasing evidence regarding the association of hyperuricemia with chronic kidney disease (CKD), cardiovascular disease, and metabolic syndrome or diabetes mellitus.

Conclusions: Important aspects need to be clarified regarding hyperuricemia predisposition to oxidative stress and its effects in order to initiate the proper treatment to determine the optimal maintenance of UA level, improving patients' long-term prognosis and their quality of life.

Keywords: cardiovascular risk; chronic kidney disease; outcome; oxidative stress; uric acid.

Figure 1

Metabolism of purine through xanthine oxidoreductases. XO, xanthine oxidase; XDH, xanthine dehydrogenase; ROS, reactive oxygen species; NADH, nicotinamide adenine dinucleotide (Modified after: [23]).

Figure 2

(A) SMCT1 and SMCT2 reabsorb Na-dependent anions and raise intra-cellular concentration. URAT1/OAT10/OAT4 exchange intracellular anions with tubular urate, which will exit the cell via GLUT9. (B) Na and alpha-ketoglutarate will enter the cell through NADC3. Basolateral OAT1/OAT3 exchanges plasma urate with intracellular alpha-ketoglutarate. Intracellular urate exit is accomplished through voltage channels NPT1/NPT4 or ATP-driven MRP4. SMCT1,sodium-monocarboxylate co-transporter 1; SMCT2, sodium-monocarboxylate co-transporter 2; Na⁺, sodium; K⁺, potassium; URAT1, urate transporter 1; OAT10, organic anion transporter 10; OAT4, organic anion transporter 4; OAT1, organic anion transporter 1; OAT3, organic anion transporter 3; MRP4, multidrug resistance protein 4; ABCG2, adenosine triphosphate binding cassette subfamily G member 2; NPT1, Na-phosphate transporter 1; NPT4, Na-phosphate transporter 4; GLUT9, glucose transporter 9; NADC3, sodium-dependent dicarboxylate cotransporter 3 (Modified after [35]).