Adriamycin-induced nephropathy as a model of chronic progressive glomerular disease

Abstract

Serial changes in urine protein, blood chemistry, and histology of the kidney were investigated in rats for 28 weeks after injections of adriamycin (ADR). Massive proteinuria, hypoalbuminemia, and hyperlipidemia were observed at week 4 and throughout the experiment. Both BUN and serum creatinine began to increase at week 16 and reached the uremic level at week 28. Light microscopic study of the kidney demonstrated a normal appearance at week 4, vacuole formation in glomerular tuft and weeks 8 and 12, focal and segmental glomerular sclerosis at weeks 16 and 20, and extensive glomerular sclerosis with tubulointestinal degenerations at weeks 24 and 28. Immunohistologically, IgM with a small amount of IgG and C3 appeared in the sclerosing glomeruli from week 16. Aggregated human IgG, injected intravenously at week 24, had accumulated mainly in the glomeruli. Electron microscopy revealed degenerative changes of glomerular epithelial cells with small vacuoles in the cytoplasm at week 4. Size of vacuoles increased at the later stage. In conclusion, ADR produced chronic, progressive glomerular changes in rats, which led to terminal renal failure. The segmental glomerular sclerosis and IgM-dominant glomerular deposition in these animals are similar to pathological characteristics of focal and segmental glomerular sclerosis seen clinically.