Oral adsorbent prevents reduction of anionic sites of the glomerular basement membrane in diabetic nephropathy.
BACKGROUND
AST-120, an oral adsorbent, inhibits progression of diabetic nephropathy by reducing albuminuria. The purpose of the present study was to explore the mechanism underlying the protective effect of AST-120 against albuminuria.


METHODS
Twenty-four male Sprague-Dawley rats underwent intravenous injection of streptozotocin and subsequent uninephrectomy. Half of the rats were fed standard rat chow, and the other half were fed rat chow containing AST-120. All rats were killed at week 6 after a clearance study.


RESULTS
There were no significant differences in body weight, kidney weight, urinary volume, blood pressure, blood glucose or inulin clearance between the two groups at week 6. However, urinary albumin excretion at week 6 was significantly lower in the AST-120 group than in the control group (p < 0.05). Light microscopic observation showed that the planar area of glomeruli was significantly smaller in the AST-120 group than in the control group (p < 0.01), and the shortest diameter of proximal tubules was less in the AST-120 group than in the control group (p < 0.01). Electron microscopic observation showed a significantly greater number of anionic sites on the lamina rara externa of the glomerular basement membrane in the AST-120 group than in the control group (p < 0.01).


CONCLUSIONS
We conclude that AST-120 reduces albuminuria by preventing the decrease in the number of anionic sites in the glomerular basement membrane in rats with diabetic nephropathy. In addition, AST-120 inhibits the appearance of glomerular and tubular hypertrophy.
Okada
Kazuyoshi
K
Division of Nephrology and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. kokada@med.nihon-u.ac.jp
Matsumoto
Koichi
K
Takahashi
Susumu
S
D000284:Administration, Oral; D000327:Adsorption; D000419:Albuminuria / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D002244:Carbon / Q000008:administration & dosage / Q000494:pharmacology*; D003928:Diabetic Nephropathies; D050533:Glomerular Basement Membrane / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D006984:Hypertrophy; D007684:Kidney Tubules / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D008854:Microscopy, Electron; D008863:Microspheres; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010087:Oxides; D002244:Carbon; C040896:AST 120