Studies on the Mechanism of Experimental Proteinuria

Abstract

Proteinuria may be produced in the experimental animal in a variety of ways. One of the simplest and most convenient methods is injection of the kidney enzyme, renin.Picketing and Prinzmetal (1) were the first to notice that proteinuria was increased following renin administration to the rabbit. Brandt and Gruhn (2) confirmed this finding, and by studying the simultaneous excretion of injected hemoglobin, concluded that renin does not significantly alter the glomerular permeability, but rather increases proteinuria by diminishing tubular reabsorption of protein from the glomerular filtrate. Shortly after this, Addis, Barrett, Boyd, and Ureen (3) discovered that renin produced an intense, though transient, proteinuria in the rat. Since inactivation of renin, with respect to its pressor effect, led to a loss of its capacity to induce proteinuria, and since repeated injections of renin, at suitable intervals, led to a diminution in the proteinuric as well as the pressor property of renin, these workers concluded that this form of proteinuria is dependent on the pressor action of renin. Rather and Addis (4) reported that the athrocytosis of simultaneously administered hemoglobin or bovine albumin by the cells lining the proximal convoluted tubule is not inhibited by renin, and stated that Brandt and Gruhn's hypothesis, that renin inhibits the tubular reabsorption of protein, is not supported by their experiments. More recently, Lippman, Ureen, and Oliver (5) have restudied the effect of renin on the excretion of injected hemoglobin. From a combination of morphological and functional data these workers conclude that renin causes an increase in glomerular permeability to hemoglobin and decreases the tubular reabsorption of this substance. Hence, conflicting views are expressed concerning the mechanism whereby renin produces an increased excretion of protein in the urine.

Studies on the Mechanism of Oliguria in a Model of Unilateral Acute Renal Failure

“…In addition, the epithelial changes after angiotensin also occurred after a nonpressor dose and were invariably associated with proteinuria. Since these changes are quite like those reported in lipoid nephrosis (41), it is possible that this may be related to the proteinuria seen after the administration of renin (42,43) or angiotensin II (40). The infusion of norepinephrine has not been reported to cause proteinuria.…”

THE EFFECT OF pH ON THE FILTRATION, REABSORPTION, AND EXCRETION OF PROTEIN BY THE RAT KIDNEY*

“…This union cannot be disrupted by incubating dye-labeled protein with liver slices (18). In vivo, the injection of T-1824 in doses up to 2.5 times greater than the amount used in these present studies does not result in the appearance of free dye in the serum (19) or in the urine (20); nor can dye be detected within the PCT cells immediately after its injection (19).…”

Glomerular permeability of macromolecules. Effect of molecular configuration on the fractional clearance of uncharged dextran and neutral horseradish peroxidase in the rat.

“…The filtration of macromolecules across the glomerular capillary wall is determined by the structural characteristics of the filter (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), glomerular hemodynamics (13)(14)(15)(16)(17)(18)(19)(20)(21), and molecular parameters of the solute. Molecular determinants include the molecular radius (22)(23)(24)(25) and the net molecular charge (26)(27)(28)(29)(30).…”

“…We conclude that other molecular parameters such as shape, flexibility, and deformability play important roles in the transport of macromolecules across the extracellular matrix that constitutes the glomerular filter. INTRODUCTION The filtration of macromolecules across the glomerular capillary wall is determined by the structural characteristics of the filter (1-12), glomerular hemodynamics (13)(14)(15)(16)(17)(18)(19)(20)(21), and molecular parameters of the solute. Molecular determinants include the molecular radius (22)(23)(24)(25) and the net molecular charge (26-30).…”