Advanced glycation end products induce glomerular sclerosis and albuminuria in normal rats

Helen Vlassara, Liliane J. Striker, Saul Teichberg, Hubert Fuh, Yong Ming Li, Michael W Steffes

Research output: Contribution to journalArticle

394 Citations (Scopus)

Abstract

High levels of tissue advanced glycation end products (AGEs) that result from the spontaneous modification of proteins by glucose occur in diabetes and aging. To address the potential pathogenic role of AGEs in the glomerulosclerosis of diabetes or nephrosclerosis of aging, doses of AGE- modified rat albumin (25 mg per kg per day, i.v.) sufficient to elevate circulating AGE levels to the range of diabetic serum were administered daily to healthy rats alone or in combination with the AGE inhibitor aminoguanidine. After 5 months, the AGE content of renal tissues in AGE- treated rats rose to 50% above controls (P < 0.025), whereas serum contained 2.8-fold greater AGE levels (P < 0.025). Light and electron microscopy of kidneys from AGE-treated rats revealed a more than 50% increase in glomerular volume compared to controls (P < 0.001), significant periodic acid/Schiff reagent-positive deposits, basement membrane widening, and mesangial extracellular matrix increase and indicated significant glomerulosclerosis compared to untreated (P < 0.002) or albumin-treated controls (P < 0.002). These changes were associated with significant loss of protein (P < 0.005) and albumin (P < 0.002) in the urine of AGE-treated rats compared to controls. Cotreatment with aminoguanidine markedly limited both the structural and functional defects. These in vivo data demonstrate that AGEs influence glomerular structure and function in a manner leading to glomerulosclerosis. The effects are AGE-specific, as they are ameliorated by a pharmacological AGE inhibitor, aminoguanidine.

Original languageEnglish (US)
Pages (from-to)11704-11708
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number24
DOIs
StatePublished - Nov 22 1994

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Advanced Glycosylation End Products
Albuminuria
Sclerosis
Albumins
Glomerular Mesangium
Nephrosclerosis
Kidney
Periodic Acid
Serum
Basement Membrane
Electron Microscopy
Proteins
Urine
Pharmacology
Light
Glucose
pimagedine

Keywords

  • aging
  • aminoguanidine
  • animal model
  • diabetes
  • renal insufficiency

Cite this

Advanced glycation end products induce glomerular sclerosis and albuminuria in normal rats. / Vlassara, Helen; Striker, Liliane J.; Teichberg, Saul; Fuh, Hubert; Li, Yong Ming; Steffes, Michael W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 24, 22.11.1994, p. 11704-11708.

Research output: Contribution to journalArticle

Vlassara, Helen ; Striker, Liliane J. ; Teichberg, Saul ; Fuh, Hubert ; Li, Yong Ming ; Steffes, Michael W. / Advanced glycation end products induce glomerular sclerosis and albuminuria in normal rats. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 24. pp. 11704-11708.
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