Permeation of macromolecules into the renal glomerular basement membrane and capture by the tubules

Abstract

SignificanceHuman kidneys contain ∼2 x 106 glomeruli that produce ∼180 L per day of primary filtrate. Downstream tubules reabsorb most of the water, salt, and desirable low-molecular weight substances, leaving 1 to 2 L per day of urine containing undesirable waste products. Currently, most investigators think that the primary filtrate is low in protein because fluid exiting the glomerulus passes through slits spanned by a diaphragm that acts as a low-porosity molecular sieve. Our experiments challenge this view; they show that size-dependent permeation into the glomerular basement membrane and into a gel-like coat that covers the slits, together with saturable tubular reabsorption, determines which macromolecules reach the urine. The slit diaphragm is essential for capillary structure but may not directly determine glomerular size selectivity.

What Is the Glomerular Ultrafiltration Barrier?

“…11 This model explains why mutations that affect the slit diaphragm, its linkage to the cytoskeleton, or the cytoskeleton itself cause nephrotic syndrome and importantly, takes into account mechanisms involving cellular regulation of GBM protein organization through integrin-a3b1. The model, like a recently presented one, 12 also has explanatory power regarding the varied phenotypes arising from mutations in GBM components. 13 Mutations affecting laminin-521 disproportionately derange the GFB compared with collagen IV and agrin.…”

Identification of Factors Complicating Bioluminescence Imaging

“…The accumulation of teLuc in the bladder suggests that the small size of teLuc makes it permeable to the glomerular basement membrane. 38 teLuc accumulated in urine still remains enzymatically active. In fact, when mice injected with teLuc-labeled cells were imaged, the bladder area often showed the strongest signals.…”

<p>Internalization and effects on cellular ultrastructure of nickel nanoparticles in rat kidneys</p>

“…[27][28][29] In this study, the cellular ultrastructural localization of NiNPs was found to be within vacuoles or were found as free individual particles or aggregated/accumulated particles in renal tubule epithelial cells, and in the interstitium close to the basement membrane of the cells lining the renal tubules. The accumulation of NiNPs at the PT membrane may be due to many factors; firstly, difficulty in their indirect penetration rate leading to accumulation, secondly: due to their high extracellular concentration, 30,31 the repetitive daily injections, thirdly: due to their large size. Moreover, physicochemical properties of the NPs could be another possible factor behind their aggregation, accumulation, and adhesion.…”