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Combination therapy with benazepril and oral adsorbent ameliorates progressive renal fibrosis in uremic rats.

AbstractBACKGROUND/AIMS:
The administration of an angiotensin-converting enzyme (ACE) inhibitor or an oral adsorbent, AST-120 (Kremezin), prevents the progression of renal failure. This study was designed to determine the additional effects of AST-120 combined with an ACE inhibitor, benazepril, on the progression of renal fibrosis in uremic rats.
METHODS:
5/6-nephrectomized uremic rats were divided into control uremic rats (CRF group), benazepril-treated uremic rats (CRF+B group) and uremic rats receiving benazepril and AST-120 (CRF+BK group). After 14 weeks of treatment renal function and pathological changes were investigated.
RESULTS:
The progression of renal dysfunction was delayed in both the CRF+B and CRF+BK groups as compared with the CRF group. In the CRF+BK group, the level of serum and urinary indoxyl sulfate and the tubular accumulation of indoxyl sulfate decreased. Both the CRF+B and CRF+BK groups showed lower glomerular sclerosis indices than the CRF group. In the CRF+BK group, but not the CRF+B group, the interstitial fibrosis area and the expression of transforming growth factor (TGF) beta1 and tissue inhibitor of metalloproteinases (TIMP) 1 were decreased as compared with the CRF group. Furthermore, the CRF+BK group showed a smaller interstitial fibrosis area and a lower renal osteopontin expression than the CRF+B group.
CONCLUSION:
Combination therapy of benazepril and AST-120 is more effective than benazepril alone in retarding the progression of interstitial fibrosis by reducing the expression of TGF-beta 1, TIMP-1 and osteopontin.
AuthorsIsao Aoyama, Kaoru Shimokata, Toshimitsu Niwa
JournalNephron (Nephron) Vol. 90 Issue 3 Pg. 297-312 (Mar 2002) ISSN: 1660-8151 [Print] Switzerland
PMID11867951 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2002 S. Karger AG, Basel
Chemical References
  • Angiotensin-Converting Enzyme Inhibitors
  • Benzazepines
  • Oxides
  • SPP1 protein, human
  • Sialoglycoproteins
  • Spp1 protein, rat
  • TGFB1 protein, human
  • Tgfb1 protein, rat
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Osteopontin
  • Carbon
  • AST 120
  • Indican
  • benazepril
Topics
  • Adsorption
  • Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
  • Animals
  • Benzazepines (therapeutic use)
  • Blood Pressure (physiology)
  • Carbon (therapeutic use)
  • Cells, Cultured
  • Disease Progression
  • Drug Therapy, Combination
  • Fibroblasts (metabolism)
  • Fibrosis
  • Humans
  • In Situ Hybridization
  • Indican (blood, urine)
  • Kidney (drug effects, pathology, physiopathology)
  • Kidney Diseases (drug therapy, pathology, physiopathology)
  • Male
  • Nephrectomy
  • Nephrosclerosis (drug therapy, pathology, physiopathology)
  • Osteopontin
  • Oxides (therapeutic use)
  • Rats
  • Rats, Sprague-Dawley
  • Sialoglycoproteins (genetics, metabolism)
  • Tissue Inhibitor of Metalloproteinase-1 (metabolism)
  • Transforming Growth Factor beta (genetics, metabolism)
  • Transforming Growth Factor beta1
  • Uremia (drug therapy)

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