Adriamycin-induced chronic proteinuria: A structural and functional study

M. P. O'Donnell, L. Michels, B. Kasiske, L. Raij, W. F. Keane

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Abstract

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 < 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.

Original languageEnglish (US)
Pages (from-to)62-67
Number of pages6
JournalJournal of Laboratory and Clinical Medicine
Volume106
Issue number1
StatePublished - Dec 1 1985

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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O'Donnell, M. P., Michels, L., Kasiske, B., Raij, L., & Keane, W. F. (1985). Adriamycin-induced chronic proteinuria: A structural and functional study. Journal of Laboratory and Clinical Medicine, 106(1), 62-67.