An oral adsorbent ameliorates renal overload of indoxyl sulfate and progression of renal failure in diabetic rats

Am J Kidney Dis. 2001 Jan;37(1 Suppl 2):S7-S12. doi: 10.1053/ajkd.2001.20731.

Abstract

Otsuka Long-Evans Tokushima Fatty (OLETF) rats were established as a new model of non-insulin-dependent diabetes mellitus. An oral adsorbent, AST-120, is effective in removing such uremic toxins as indoxyl sulfate and delays the progression of chronic renal failure (CRF). This study was designed to determine the effects of AST-120 on the progression of CRF in uninephrectomized OLETF (1/2NxOLETF) rats and the localization of indoxyl sulfate in their kidneys. Four weeks after unilateral nephrectomy, 14 OLETF rats were divided into two groups; AST-120-administered and control 1/2NxOLETF rats. Long-Evans Tokushima Otsuka rats, which are genetically similar to the OLETF rats but not diabetic, were also included. After the administration of AST-120 for 36 weeks, we examined the effects of AST-120 on renal functional and pathological changes in the three groups. The control 1/2NxOLETF rats showed marked hyperglycemia, hyperlipidemia, renal failure, glomerular sclerosis, and tubulointerstitial injury. The administration of AST-120 to the 1/2NxOLETF rats retarded the progression of renal dysfunction and fibrosis, as well as hyperlipidemia, and reduced serum and urinary levels of indoxyl sulfate. Immunohistochemistry showed that AST-120 markedly reduced the overload of indoxyl sulfate in tubular epithelial cells, especially dilated tubules, of the 1/2NxOLETF rats. In conclusion, AST-120 delayed the progression of renal failure and fibrosis in 1/2NxOLETF rats and decreased the overload of indoxyl sulfate on renal tubular cells.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Urea Nitrogen
  • Carbon / pharmacology*
  • Cholesterol / blood
  • Creatinine / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / prevention & control
  • Disease Progression
  • Immunohistochemistry
  • Indican / metabolism*
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / prevention & control*
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Male
  • Oxides / pharmacology*
  • Rats
  • Rats, Inbred OLETF
  • Rats, Long-Evans
  • Treatment Outcome
  • Triglycerides / blood

Substances

  • Oxides
  • Triglycerides
  • Carbon
  • AST 120
  • Cholesterol
  • Creatinine
  • Indican