Fig. 4.

Uric acid undergoes a dynamic process of elimination and reabsorption, primarily orchestrated by the kidneys (two-thirds) and the intestines (one-third). In the nephron, filtration of water and solutes occurs within the glomerular capsule, followed by tubular reabsorption, predominantly mediated by the proximal convoluted tubule. Concurrently, tubular secretions extract uric acid from peritubular capillaries, secreting it into the tubular fluid for urinary excretion. Urate transporters in renal proximal tubule epithelial cells actively mediate the secretion and reabsorption of urate, thus determining the net excretion levels from the kidney. In the renal proximal tubule, SLC22A12 (URAT1), SLC17A1 (NPT1), and SLC22A11 (OAT4) located on the apical membrane facilitate reabsorption. SLC2A9 (GLUT9), found in both the apical and basolateral membrane tubules, is a long isoform that mediates the basolateral efflux of urate back into circulation. For excretion, SLC22A6 (OAT1) and SLC22A8 (OAT3) on the basolateral membrane facilitate urate entry into the renal tubules. ABCG2 (BCRP) and SLC17A3 (NPT4), positioned on the apical side, contribute to the secretory transport of urate into the tubule lumen for urinary excretion. In intestinal metabolism, uric acid is actively secreted into the intestinal lumen primarily by the transporter ABCG2, underscoring the role of the intestines in urate homeostasis