The implications of the changes in the nature of the urinary proteins which occur in albumin overload-induced proteinuria in normal mice.

Mice with normal urine were given daily injections of human serum albumin for 7 days. Blood and urine samples were obtained at regular intervals during the first 24 h and daily throughout the injection period, and for 6 days after the injections had been stopped. Control mice which received saline injections were studied in a similar fashion. Albumin-injected mice developed peak urinary total protein concentrations and peak incidence of high and medium mol. wt proteinuria after the third daily injection. Despite the fact that plasma total protein and plasma albumin concentrations remained elevated, both the total urinary protein and the incidence of large proteins fell after the third day. Saline-injected mice did not show unusual changes in the range of total urinary protein, but over the first 3 days a small percentage developed proteinuria. Explanations for the observed changes were sought on the basis that glomerular basement membranes are thixotropic gels and are therefore pressure-dependent. It was concluded that the changes in urinary proteins could be due to the effects of combinations of the following factors: (a) the existence of an auto-regulatory mechanism which by stimulating afferent arteriolar constriction reduced glomerular pressure; (b) the reduction of the protein content of a proteinaceous filtrate because of protein absorption by glomerular epithelial cells; and (c) as both saline-injected and albumin-injected mice developed proteinuria during the first 3 days, it is speculated that volume expansion also contributed to the proteinuria, through its effects at the level of efferent arterioles.