title: Hyperuricemia causes glomerular hypertrophy in the rat.
abstract: OBJECTIVE
  Rats with mild hyperuricemia develop systemic hypertension, interstitial renal disease, afferent arteriolopathy, and increased renin expression [Mazzali et al.: Am J Physiol 2002;6:F991-F997]. We hypothesized that hyperuricemia might also induce glomerular changes.
  
  
  METHODS
  We reviewed renal biopsies of rats previously made hyperuricemic for 7 weeks with the uricase inhibitor, oxonic acid. Controls included normal rats and oxonic acid-treated rats administered allopurinol, benziodarone, hydrochlorothiazide, or enalapril. Glomeruli were examined for size (computer image analysis) and structure (histology). An additional group of rats were administered oxonic acid or control diet for 6 months.
  
  
  RESULTS
  Renal biopsies showed that hyperuricemic rats had a 30% increase in glomerular tuft area (p < 0.01); these changes were prevented by allopurinol and benziodarone. Control of blood pressure with hydrochlorothiazide did not prevent the development of glomerular hypertrophy, whereas enalapril partially reduced the glomerular hypertrophy. Prolonged hyperuricemia was associated with the development of microalbuminuria (p < 0.05) and glomerulosclerosis (22 vs. 10%, p < 0.05) compared to control rats.
  
  
  CONCLUSIONS
  Hyperuricemic rats develop glomerular hypertrophy that can be prevented in part by ACE inhibitor therapy. Prolonged hyperuricemia is associated with the development of glomerulosclerosis in the rat.
authors.affiliation: Department of Medicine-Nephrology, Baylor College of Medicine, Houston, Tex 77030, USA. takahiko@bcm.tmc.edu
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Marilda
authors.initials: M
authors.lastname: Mazzali
authors.forename: Duk-Hee
authors.initials: DH
authors.lastname: Kang
authors.forename: John
authors.initials: J
authors.lastname: Kanellis
authors.forename: Susumu
authors.initials: S
authors.lastname: Watanabe
authors.forename: Laura G
authors.initials: LG
authors.lastname: Sanchez-Lozada
authors.forename: Bernardo
authors.initials: B
authors.lastname: Rodriguez-Iturbe
authors.forename: Jaime
authors.initials: J
authors.lastname: Herrera-Acosta
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D006984:Hypertrophy; D033461:Hyperuricemia / Q000150:complications*; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley