Adriamycin-induced chronic proteinuria: a structural and functional study.
Focal, segmental glomerulosclerosis is frequently associated with chronic proteinuria and progressively declining renal function in humans as well as in experimental models of glomerular disease. Although little is known regarding the pathogenesis of this lesion, persistent, massive proteinuria has been associated with a poor prognosis. The administration of adriamycin to rats results in proteinuria of glomerular origin. We used this model to study the glomerular functional and structural alterations associated with proteinuria of 4 to 5 weeks duration. Studies of single nephron function revealed a 34% reduction in nephron plasma flow and a 50% decline in the glomerular ultrafiltration coefficient in rats given adriamycin. Single nephron glomerular filtration rate, however, was only modestly reduced (27%), because of an 8.0 mm Hg elevation of mean transcapillary hydraulic pressure difference (P less than 0.05). Morphologically, glomeruli of adriamycin-treated rats demonstrated significantly increased mesangial matrix and cellularity. In addition, glomerular capillaries frequently appeared enlarged, and epithelial cell bleb formation was evident. Focal glomerulosclerosis, however, was only rarely seen. The functional and morphologic characteristics of chronic adriamycin nephrosis are different from those associated with chronic proteinuria induced by repetitive administration of aminonucleoside of puromycin. Comparison of the two models suggests that the development of focal glomerulosclerosis can be dissociated from proteinuria and elevations of intraglomerular hydraulic pressures.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009399:Nephrons / Q000503:physiopathology; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004317:Doxorubicin