Glomerular podocytes are highly specialized cells with a complex cytoarchitecture. Their most prominent features are interdigitated foot processes with filtration slits in between. These are bridged by the slit diaphragm, which plays a major role in establishing the selective permeability of the glomerular filtration barrier. Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases. New technical approaches have led to a considerable increase in our understanding of podocyte biology including protein inventory, composition and arrangement of the cytoskeleton, receptor equipment, and signaling pathways involved in the control of ultrafiltration. Moreover, disturbances of podocyte architecture resulting in the retraction of foot processes and proteinuria appear to be a common theme in the progression of acquired glomerular disease. In hereditary nephrotic syndromes identified over the last 2 years, all mutated gene products were localized in podocytes. This review integrates our recent physiological and molecular understanding of the role of podocytes during the maintenance and failure of the glomerular filtration barrier.

Cell Biology of the Glomerular Podocyte

This review focuses on the intricate properties of the glomerular barrier. Other reviews have focused on podocyte biology, mesangial cells, and the glomerular basement membrane (GBM). However, since all components of the glomerular membrane are important for its function, proteinuria will occur regardless of which layer is affected by disease. We review the properties of endothelial cells and their surface layer, the GBM, and podocytes, discuss various methods of studying glomerular permeability, and analyze data concerning the restriction of solutes by size, charge, and shape. We also review the physical principles of transport across biological or artificial membranes and various theoretical models used to predict the fluxes of solutes and water. The glomerular barrier is highly size and charge selective, in qualitative agreement with the classical studies performed 30 years ago. The small amounts of albumin filtered will be reabsorbed by the megalin-cubulin complex and degraded by the proximal tubular cells. At present, there is no unequivocal evidence for reuptake of intact albumin from urine. The cellular components are the key players in restricting solute transport, while the GBM is responsible for most of the resistance to water flow across the glomerular barrier.

Properties of the Glomerular Barrier and Mechanisms of Proteinuria

https://www.kidney-international.org/article/S0085-2538(15)48949-5/pdf

Pathophysiology of proteinuria

The normal kidney filters nephrotic levels of albumin retrieved by proximal tubule cells: Retrieval is disrupted in nephrotic states

https://www.kidney-international.org/article/S0085-2538(15)51517-2/pdf

Renal albumin absorption in physiology and pathology

The return of glomerular-filtered albumin to the rat renal vein

Variability of standard clinical protein assays in the analysis of a model urine solution of fragmented albumin.

https://www.ajkd.org/article/S0272-6386(01)43055-1/pdf

Immuno-unreactive albumin excretion increases in streptozotocin diabetic rats

Background. Recent studies have demonstrated that the normal glomerular capillary wall (GCW) is not charge selective to albumin. This means that albumin flux across the GCW is high. This has been confirmed in studies where albumin uptake by the tubules has been inhibited. Therefore, there must be a high capacity postglomerular retrieval pathway in normal kidneys that returns filtered albumin back to the blood supply. Methods. This study identifies the presence of glomerular filtered albumin in the renal vein from the analysis of the decrease of radioactivity in the venous effluent after the injection of a pulse of tritium labeled albumin into the renal artery in vivo and in the isolated perfused kidney (IPK). Results. The glomerular filtered albumin is returned to the blood supply by a high capacity pathway that transports this albumin at a rate of 1830 ± 292 μg/min rat kidney (n = 14) (mean ± SEM). This pathway has been identified under physiological conditions in vivo and in the IPK. The pathway is spec...

The return of glomerular filtered albumin to the rat renal vein – the albumin retrieval pathway

Exogenous albumin peptides influence the processing of albumin during renal passage. Background/Aims: This study investigates the hypothesis that there will be peptide regions in al

Gabriela A. Eppel

Papers

The return of glomerular-filtered albumin to the rat renal vein

Variability of standard clinical protein assays in the analysis of a model urine solution of fragmented albumin.

Immuno-unreactive albumin excretion increases in streptozotocin diabetic rats

The return of glomerular filtered albumin to the rat renal vein – the albumin retrieval pathway

Exogenous albumin peptides influence the processing of albumin during renal passage.