The Glomerulus

Abstract

The glomerulus, the filtering unit of the kidney, is a unique bundle of capillaries lined by delicate fenestrated endothelia, a complex mesh of proteins that serve as the glomerular basement membrane and specialized visceral epithelial cells that form the slit diaphragms between interdigitating foot processes. Taken together, this arrangement allows continuous filtration of the plasma volume. The dynamic physical forces that determine the single nephron glomerular filtration are considered. In addition, new insights into the cellular and molecular components of the glomerular tuft and their contribution to glomerular disorders are explored.Clin J Am Soc Nephrol 9: 1461-1469, 2014. doi: 10.2215/CJN.09400913 The GlomerulusThe glomerulus, the filtering unit of the kidney, is a specialized bundle of capillaries that are uniquely situated between two resistance vessels ( Figure 1). These capillaries are each contained within the Bowman's capsule and they are the only capillary beds in the body that are not surrounded by interstitial tissue. Therefore, a unique support structure is needed to maintain flow in these essential capillary units. In fact, all of the major components of the filter itself are unique compared with related structures in other capillary beds. The proximal component layer of the glomerular filter itself is a fenestrated endothelium, characterized by the presence of individual fenestrae on the order of 70-100 nm in diameter. These cells drape the luminal aspect of the capillary and permit filtration. The second layer of the filter, the glomerular basement membrane (GBM), is a complex mesh of extracellular proteins, including type IV collagen, laminins, fibronectins, and proteoglycans. The distal layer of the glomerular filter is composed of the visceral epithelial cells, or podocytes. These remarkable cells help to create the filtration slit diaphragm and serve as support to help sustain the integrity of the free-standing capillary loops. A third cell type, the mesangial cells, also contributes to the integrity of the glomerular tuft and the dynamic nature of filtration. Together, this elegant structure permits the formation of the primary glomerular filtrate that enters a space delimited by the visceral and parietal epithelial cells before modification during transit through the tubule.

Mitochondrial energetics in the kidney

“…For example, in the renal cortex, proximal tubules depend on the efficiency of oxidative phosphorylation to produce ATP that drives the active transport of glucose, ions and nutrients 8 . By contrast, glomerular cells, including podocytes, endothelial cells and mesengial cells, have lower oxidative capacity because their function is to filter blood to remove small molecules (namely, glucose, urea, water and salts) while retaining large proteins, such as haemoglobin 9 . This passive process does not directly require ATP and, therefore, glomerular cells have the ability to perform aerobic and anaerobic respiration to produce ATP for basal cell processes 10–13 .…”

Circadian regulation of renal function

“…These capillaries receive blood from the afferent arteriole, a unique “high pressure” arteriole that also functions as an endocrine organ through release of renin. The glomerular capillaries are unique in their extreme permeability and very high capillary pressure, thus facilitating the passage of fluid into the proximal tubule to begin the formation of urine [9,10]. Blood that is not filtered by the glomerulus leaves the glomerular capillaries via the efferent arterioles.…”

Kidney development and perspectives for organ engineering

“…The ECM forms a structural scaffold to support the spatial orientation of the cells. It serves also as a physical barrier/filter, such as in the case of the glomerular BM (GBM; Pollak et al 2014).…”