Nephrotic syndrome induced by dibasic sodium phosphate injections for twenty-eight days in rats.
Sprague-Dawley rats received once daily tail-vein injections of 360 mM dibasic sodium phosphate solution at 8 mL/kg for fourteen or twenty-eight days. Clinical examination revealed persistent proteinuria from three days after the first dosing and thereafter severe proteinuria from eight days or later in the phosphate-treated groups. Proteinuria developed without remission even after fourteen-day withdrawal in the fourteen-day dosed group. Phosphate-treated animals developed lipemia, hypercholesterolemia, anemia, higher serum fibrinogen levels, and lower serum albumin/globulin ratios on day 29. Renal weight increased significantly compared with control animals, and the kidneys appeared pale and enlarged with a rough surface. Histopathologically, glomerular changes consisted of mineralization in whole glomeruli, glomerular capillary dilatation, partial adhesion of glomerular tufts to Bowman's capsule, and mesangiolysis. Ultrastructural lesions such as an increased number of microvilli, effacement of foot processes, and thickening of the glomerular basement membrane, and immunocytochemical changes in podocytes, mainly decreased podoplanin-positive cells and increased desmin expression, were also conspicuous in the phosphate-treated rats for twenty-eight days. Marked tubulointerstitial lesions were tubular regeneration and dilatation, protein casts, mineralization in the basement membrane, focal interstitial inflammation, and fibrosis in the cortex. These clinical and morphological changes were similar to features of human nephrotic syndrome.
Tsuchiya
Noriko
N
Drug Safety Evaluation, Developmental Research Laboratories, Shionogi & Co., Ltd., Japan. noriko.tsuchiya@shionogi.co.jp
Torii
Mikinori
M
Narama
Isao
I
Matsui
Takane
T
D000740:Anemia / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D001806:Blood Urea Nitrogen; D050476:Bowman Capsule / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D002114:Calcinosis / Q000139:chemically induced / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D003893:Desmin / Q000378:metabolism; D004909:Erythrocyte Indices; D050533:Glomerular Basement Membrane / Q000187:drug effects / Q000648:ultrastructure; D005920:Glomerular Mesangium / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D006937:Hypercholesterolemia / Q000139:chemically induced; D006949:Hyperlipidemias / Q000139:chemically induced / Q000473:pathology; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D023421:Models, Animal; D009404:Nephrotic Syndrome / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010710:Phosphates / Q000008:administration & dosage* / Q000633:toxicity*; D011507:Proteinuria / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D003893:Desmin; D010710:Phosphates; D012709:Serum Albumin; D014280:Triglycerides; D002784:Cholesterol; D003404:Creatinine; C018279:sodium phosphate