Hyperuricemia causes glomerular hypertrophy in the rat

Takahiko Nakagawa, Marilda Mazzali, Duk Hee Kang, John Kanellis, Susumu Watanabe, Laura G. Sanchez-Lozada, Bernardo Rodriguez-Iturbe, Jaime Herrera-Acosta, Richard J. Johnson

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217 Scopus citations


Background/Aims: 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.

Original languageEnglish
Pages (from-to)2-7
Number of pages6
JournalAmerican Journal of Nephrology
Issue number1
StatePublished - 2003


  • Glomerular hypertrophy
  • Glomerulosclerosis
  • Uric acid


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