Naohiko Anzai1, Yoshikatsu Kanai, Hitoshi Endou. 1. Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Shinkawa, Mitaka-shi, Tokyo, Japan.
Abstract
PURPOSE OF REVIEW: This review focuses on recent progress in the understanding of various aspects of renal transport of urate. RECENT FINDINGS: Since the molecular cloning of the renal apical urate/anion exchanger URAT1 (SLC22A12), several membrane proteins relevant to the transport of urate have been identified. The molecular identification of two sodium-coupled monocarboxylate transporters, SMCT1(SLC5A8) and SMCT2(SLC5A12), and the emerging role of PDZ (PSD-95, DglA, and ZO-1) scaffold for renal apical transporters have led to a new concept of renal urate transport: urate-transporting multimolecular complex, or 'urate transportsome', that may form an ultimate functional unit including the sodium-coupled urate transport system by linking URAT1 and sodium-coupled monocarboxylate transporters or the coordinated apical urate uptake system by balancing reabsorptive (URAT1) and efflux (NPT1/OATv1 and MRP4) transporters. In addition, genetic variations of the URAT1 gene are associated not only with idiopathic renal hypouricemia but also with reduced renal urate excretion. SUMMARY: Although our knowledge of renal urate handling has been increased by the molecular identification of urate transport proteins and by results of genetic studies on patients with serum urate disorders, current evidence is insufficient to fully understand the precise mechanism governing the bi-directional transport of urate. Further studies are still necessary.
PURPOSE OF REVIEW: This review focuses on recent progress in the understanding of various aspects of renal transport of urate. RECENT FINDINGS: Since the molecular cloning of the renal apical urate/anion exchanger URAT1 (SLC22A12), several membrane proteins relevant to the transport of urate have been identified. The molecular identification of two sodium-coupled monocarboxylate transporters, SMCT1(SLC5A8) and SMCT2(SLC5A12), and the emerging role of PDZ (PSD-95, DglA, and ZO-1) scaffold for renal apical transporters have led to a new concept of renal urate transport: urate-transporting multimolecular complex, or 'urate transportsome', that may form an ultimate functional unit including the sodium-coupled urate transport system by linking URAT1 and sodium-coupled monocarboxylate transporters or the coordinated apical urate uptake system by balancing reabsorptive (URAT1) and efflux (NPT1/OATv1 and MRP4) transporters. In addition, genetic variations of the URAT1 gene are associated not only with idiopathic renal hypouricemia but also with reduced renal urate excretion. SUMMARY: Although our knowledge of renal urate handling has been increased by the molecular identification of urate transport proteins and by results of genetic studies on patients with serum urate disorders, current evidence is insufficient to fully understand the precise mechanism governing the bi-directional transport of urate. Further studies are still necessary.
Authors: Kate Witkowska; Kyla M Smith; Sylvia Y M Yao; Amy M L Ng; Debbie O'Neill; Edward Karpinski; James D Young; Christopher I Cheeseman Journal: Am J Physiol Renal Physiol Date: 2012-05-30
Authors: Daniel F B Wright; Stephen B Duffull; Tony R Merriman; Nicola Dalbeth; Murray L Barclay; Lisa K Stamp Journal: Br J Clin Pharmacol Date: 2015-12-29 Impact factor: 4.335