Diabetic nephropathy is a common cause of
end-stage renal disease. The administration of an oral adsorbent,
AST-120, prevents the progression of
chronic renal failure in uremic rats and undialyzed uremic patients. This study was designed to determine if
AST-120 slows the progression of
diabetic nephropathy using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of non-
insulin-dependent diabetic mellitus. At 21 weeks of age the OLETF rats were divided into 2 groups: AST-120-administered OLETF rats (n = 7), and control OLETF rats (n = 7). LETO rats, which are genetically similar to the OLETF rats but not diabetic, were also included. After the
oral administration of
AST-120 for 65 weeks, renal function and pathological changes were investigated in the 3 groups. The administration of
AST-120 to the OLETF rats attenuated the progression of glomerular
sclerosis, interstitial
fibrosis, tubular injury as well as renal dysfunction, and reduced the serum and urinary levels of
indoxyl sulfate. Furthermore,
AST-120 administration reduced the interstitial expression of
transforming growth factor (TGF)-beta(1) and
tissue inhibitor of metalloproteinase (TIMP)-1, as well as interstitial infiltration of macrophages. The TGF-beta(1)-stained interstitial area showed positive correlations with the interstitial
fibrosis area, the number of TIMP-1-positive cells, and the number of macrophages, and showed a negative correlation with
creatinine clearance. In conclusion,
AST-120 reduced the interstitial expression of TGF-beta(1) and
TIMP-1, and the interstitial infiltration of macrophages, and ameliorates the progression of
diabetic nephropathy in OLETF rats.