title: Hyperuricemia, gout and the kidney.
abstract: OBJECTIVE
  (a) To examine the latest information about renal tubular handling of uric acid, its genetic background and contribution to the causation of hyperuricemia. (b) To review the association of hyperuricemia, gout and chronic kidney damage and whether hyperuricemia is cause or effect of renal dysfunction.
  
  
  RESULTS
  The gene SLC2A9 encodes for GLUT9, an important proximal tubule transporter of uric acid. Polymorphisms of the gene have been linked to gout susceptibility and to hereditary hypouricemia. Familial childhood gout with progressive renal impairment attributable to mutations of the uromodulin (UMOD) gene is associated with reduced uromodulin in the proximal tubule cilia. Familial juvenile hyperuricemic nephropathy (FJHN) is one of three similar clinical disorders associated with uromodulin gene mutations. Genetic studies of urate transportation and of uromodulin-related nephropathy emphasize the pivotal importance of the proximal tubule in uric acid homeostasis. Studies of allopurinol and febuxostat lowering of serum urate have once again raised the tantalizing possibility that hyperuricemia is harmful to the kidneys by showing better preservation of glomerular filtration rate (GFR) in treated patients.
  
  
  CONCLUSIONS
  Renal tubular handling of uric acid is dependent on tubular transporters, one of which is GLUT9. Mutations of its gene SLC2A9 are associated with aberrations of uric acid disposal. Familial hyperuricemia due to uromodulin deficiency precedes but does not cause kidney failure. Nevertheless, both allopurinol and febuxostat treatment has sustained the hypothesis that hyperuricemia itself can have an adverse impact on kidney function.
authors.affiliation: Guys and St Thomas NHS Foundation, Trust, London, UK. terence.gibson@kcl.ac.uk
authors.forename: Terence
authors.initials: T
authors.lastname: Gibson
mesh_terms: D006073:Gout / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D033461:Hyperuricemia / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D014527:Uric Acid / Q000097:blood
chemical_list: D014527:Uric Acid