Micropuncture studies were performed in three groups of male Munich-Wistar rats 1 wk after surgery: group I, eight control rats that underwent laparotomy and were fed a normal diet; group II, nine rats that underwent right nephrectomy and segmental infarction of five-sixths of the left kidney and were fed a normal diet; and group III, seven rats that underwent the same renal ablative procedure and were fed a low protein diet. Single nephron glomerular filtration rate (SNGFR) was higher in the remnant kidney of group II rats compared with group I rats due to higher average values for mean glomerular transcapillary hydraulic pressure difference (delta P) and initial glomerular plasma flow rate (QA) in group II. Glomeruli in remnant kidneys of group II showed striking alterations in morphology, including epithelial cell protein reabsorption droplets, foot process fusion, and mesangial expansion. Group III rats demonstrated a mean SNGFR not statistically different from that of group I, but significantly less than that of group II rats. This lack of absolute hyperfiltration in remnant glomeruli of group III rats relative to group I obtained because QA and delta P did not increase above values found in group I. The glomerular structural lesions seen in group II were also largely attenuated in group III. These studies demonstrate that alterations in glomerular hemodynamics associated with renal ablation are accompanied by structural lesions and suggest that sustained single nephron hyperfiltration may have maladaptive consequences by damaging remnant glomeruli.

Perfusion of rat kidneys with the polycation protamine sulfate caused glomerular epithelial alterations resembling those observed in human and experimental nephrotic states. The changes included swelling, blunting, and flattening of epithelial foot processes, were accompanied by decreased stainability of glomerular anionic sites, and were largely reversed by subsequent perfusion with the polyanion heparin.

TWO characteristics distinguish glomerular ultrafiltration from transcapillary exchange in other organs: 1 ' 2 (1) the glomerulus almost completely excludes plasma proteins of the size of albumin and larger from its filtrate, and (2) the glomerular capillary wall exhibits an extraordinarily high permeability to water and small solutes. Up to 33% of intraglomerular plasma normally is converted into a virtually protein free filtrate. 2 Determinants of this process are: (1) properties of the filter and of the molecules filtered, (2) interactions of molecules and the filter, and (3) glomerular plasma flow and the balance of hydrostatic and osmotic forces across the filter according to Starling's hypothesis. This review will discuss the effects of filter structure, molecular properties, and filter-molecule interactions on glomerular filtration.

Beef liver catalase (mol wt 240,000) was injected intravenously into normal rats and rats made nephrotic with aminonucleoside of puromycin. The localization of the tracer in the kidneys was then studied by ultrastructural cytochemistry, 3 min–12 hr after injection. Passage of catalase into the urinary space in normal rats was restricted by the basement membrane and by the epithelial slit pore. Nephrotic glomeruli showed extensive fusion of foot processes and formation of pockets and vacuoles in the fused epithelium; within 3 min after injection, catalase appeared in basal pockets, epithelial vacuoles, and the urinary space. Residual slit pores and close junctions in fused epithelium were impermeable to catalase. These studies indicate that alteration of the epithelial cells and basement membrane is responsible for protein leakage in aminonucleoside nephrosis.

Massive proteinuria is one of the major manifestations of the nephrotic syndrome and results in hypoproteinemia, decreased colloid osmotic pressure, and edema. In spite of considerable investigation, the mechanism of proteinuria in the nephrotic syndrome remains poorly understood.The available evidence suggests that increased glomerular permeability rather than tubular secretion or dimlnlghed tubular reabsorption is the cause of protein loss (1-3), but the ultrastructural and biochemical bases for glomerulax leakage have not been clearly identified. Studies employing ferritin as an electron microscope tracer (4, 5) have suggested that the glomerular basement membrane is the normal filtration barrier to this large protein, and that increased basement membrane permeability can account for proteinuria in experimental aminonucleoside nephrosis. In the ferritin studies only small amounts of tracer escaped into the urinary space; thus the mechanism of prorein transfer across the glomerular epithelium was not clarified. It is the glomerular epithelium that undergoes the most significant fine structural changes in human lipoid and experimental aminonudeoside nephrosis.The availability of sensitive ultrahistochemical methods for locafization of enzyme tracers of different molecular weights (6--8) has prompted us to reexamine the ultrastructural events in the nephrotic syndrome with the use of such tracers. In the present paper we report on the localization of horseradish peroxidase, a relatively small molecular weight protein (mol wt 40,000) which passes freely across the basement membrane (7) and thus can be used to study the mode of transepithelial passage of leaking proteins.