New rat model induced by anti-glomerular basement membrane antibody shows severe glomerular adhesion in early stage and quickly progresses to end-stage renal failure.
The aim of the present study was to introduce a new anti-glomerular basement membrane nephritis model in which plasma creatinine levels dramatically increased only 4 weeks after a single administration of rabbit antirat glomerular basement membrane antibody in Sprague-Dawley rats. According to renal morphology, glomerular lesions characterized by mesangial expansion and adhesion of the glomerular tuft to Bowman's capsule were observed in the early stage at day 7 after disease induction; adhesion was detected in approximately 90% of glomeruli 14 days after antibody injection. After 21 days the rats exhibited pronounced glomerulosclerosis/hyalinosis and severe tubulointerstitial lesions characterized by interstitial fibrosis. Urinary podocytes excreted in nephritis rats were studied and it was found that urinary podocyte loss might be closely related to progression of renal injury. Because this new model simply and reproducibly demonstrates development of end-stage renal disease, it will be beneficial for elucidating mechanisms by which chronic renal injury irreversibly progresses, as well as for developing therapeutic agents for chronic renal failure.
Nakano
Yoshimasa
Y
First Institute of New Drug Discovery, Otsuka Pharmaceutical, Tokushima, Japan.
Hirano
Takahiro
T
Uehara
Kenji
K
Nishibayashi
Seiji
S
Hattori
Katsuji
K
Aihara
Miki
M
Yamada
Yoshihisa
Y
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D002448:Cell Adhesion; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D050533:Glomerular Basement Membrane / Q000276:immunology*; D015433:Glomerulonephritis, Membranous / Q000209:etiology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology*; D008297:Male; D050199:Podocytes / Q000473:pathology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000209:etiology* / Q000473:pathology; D016482:Urinalysis; D014556:Urine / Q000166:cytology
D000906:Antibodies; D003404:Creatinine