GLOMERULAR LESIONS AND THE NEPHROTIC SYNDROME IN RABBITS GIVEN SACCHARATED IRON OXIDE INTRAVENOUSLY

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Abstract
Intravascular precipitates, comprised at least in part of iron, formed regularly in rabbits given one or more injections of a saccharated iron oxide preparation intravenously, and these lodged in numerous capillaries throughout the body, particularly those of the lungs and kidneys. Large numbers of the brownish precipitates remained in the capillaries of the renal glomeruli during the first few days following injection of the iron, but most of them disappeared after 5 to 7 days, with only moderate amounts of brown pigment remaining in the endothelial cells of the renal glomeruli. Signs of acute injury of the glomerular tufts—namely) pyknosis of some of the endothelial cells, margination of leukocytes within the glomerular capillaries, and slight proliferation of the epithelial cells—also developed some 5 to 7 days following injection of the iron, along with marked proteinuria, which proved transitory if no further injections were given. When the iron preparation was given repeatedly over prolonged intervals, however, the proteinuria persisted and became extreme, and hypoproteinemia developed, often with hypercholesterolemia and transitory edema as well. Histological studies of the kidneys of rabbits manifesting the nephrotic syndrome, as just described, disclosed that virtually all the renal glomeruli were greatly altered, mainly owing to proliferation of the epithelial cells, together with some fibrosis and atrophy. Some of the rabbits having marked proteinuria and other functional changes eventually developed azotemia following repeated injections of the iron, and several of them lost weight and died; the renal glomeruli of these animals showed changes like those just described, but the alterations were more extensive. Considered together, the findings provide evidence that the intravascular precipitates first occluded the glomerular capillaries for a period of several days following injection of the iron and then largely disappeared from them just prior to the development of morphologic signs of glomerular injury and proteinuria. Hence the possibility was considered that the intracapillary precipitates might have produced acute injury to the walls of the glomerular capllaries through the agency of anoxia. But it is plain that the findings of the present study do not disclose the essential nature of the anatomical change responsible for the proteinuria, or the means whereby this was produced. The findings as a whole were briefly considered in relation to the pathogenesis of the nephrotic syndrome as it occurs naturally in human beings.