Podocytes are key—although albumin never reaches the slit diaphragm

High glucose reduces megalin-mediated albumin endocytosis in renal proximal tubule cells through protein kinase B O-GlcNAcylation

“…Diabetes mellitus is a major cause of progression to end-stage renal disease, and albuminuria is a good marker of this process (1,2). The role of albumin reabsorption in proximal tubule (PT) 2 cells has emerged as an important factor in the genesis of albuminuria observed in the early stages of diabetes (3)(4)(5). Albumin reabsorption in these cells involves receptor-mediated endocytosis, with megalin as a central receptor (6,7).…”

Inverse correlation between vascular endothelial growth factor back-filtration and capillary filtration pressures

“…First, forced filtration generates an electrical field across the glomerular filter (streaming potential), which is proportional to filtration pressures (and SNGFR). Secondly, negatively charged plasma proteins are repelled by electrophoresis (electromigration) from entering the filter (Figure 5B, black arrow in Step 2) [20,29,[34][35][36][37][38]. As shown in Figure 5C, the electrokinetic model predicts a proportional increase in VEGF back-filtration with increasing GFR.…”

“…The electrokinetic model is an expansion of the pore model, which considers also electrical effects [20,29,[34][35][36][37][38]. According to this model, glomerular filtration works in two steps, which occur simultaneously (Figure 5B).…”

A novel model of nephrotic syndrome results from a point mutation in Lama5 and is modified by genetic background

“…There are several possible mechanisms whereby the altered GBM composition could cause the nephrotic phenotype. Firstly, based on the electrokinetic filtration model, the electric field generated across the GFB influences the passage of albumin through the GFB, dragging it towards the capillary lumen by electrophoresis [55,56]. The altered composition of the GBM in Lama5 E884G/E884G mice, may cause a more fluid ECM, and interfere with the generation of a homogeneous streaming potential, resulting in reduced electrophoresis and therefore proteinuria.…”