Fig. 1 |. The glomerulus in health and disease.

a | The healthy adult glomerulus encapsulated in Bowman’s capsule. The juxtaglomerular apparatus (JGA) is located next to the vasculature of the glomerulus, enabling macula densa cells to detect sodium chloride concentrations within the distal tubule and communicate accordingly with the granular cells of the afferent arteriole to regulate renin release and hence filtration rates and blood pressure. The afferent arteriole delivers blood to a capillary network that is surrounded in large part by the glomerular basement membrane (GBM). There are regions of the capillaries, however, that have no GBM separating them from the mesangium. Mesangial cells and the matrix they produce provide structural support for the glomerular tuft. The endothelial layer is fenestrated and is covered by a negatively charged glycocalyx made up of proteoglycans and adsorbed plasma proteins. The tri-layered filtration barrier consists of podocyte foot processes, GBM and capillary endothelial cells. Neighbouring podocyte foot processes interdigitate and are connected by slit diaphragms to form a barrier that restricts the passage of large molecules from the capillaries into the Bowman’s space. b | In patients with diabetic kidney disease, the glomerulus is characterized by reduced resistance of the afferent capillary and increased resistance of the efferent arteriole (not shown) as well as a thickened GBM, podocyte foot process effacement (that is, loss of structural features that results in spreading out), mesangial cell proliferation, increased mesangial matrix deposition and some loss of glycocalyx components. c | Patients with glomerular hypertension show a decreased capillary diameter, GBM thickening, podocyte foot process effacement, mesangial cell proliferation, increased mesangial matrix deposition and glycocalyx abnormalities. d | Patients with glomerulonephritis also show a decreased capillary diameter, podocyte foot process effacement, mesangial cell proliferation, increased mesangial matrix deposition and glycocalyx abnormalities as well asthepresence of neutrophilsand, insomeforms, depositionofimmune (antigen–antibody) complexes. The antigen that is involved in immune complexes can be either a circulating antigen or a component of the GBM or podocytes. In disease states, loss of podocytes results in regions of glomeruli that lack a filtration barrier. This loss manifests clinically as proteinuria.