The glomerulus: the sphere of influence

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.

Keywords: glomerular filtration; glomerulus; renal physiology.

Figure 1.

Structure of the renal corpuscle, looking into the Bowman’s capsule at glomerular capillary tuft. The capsule is lined with parietal epithelium, which gives way to the cells of the proximal tubule at the urinary pole on the right. At the left, the vascular pole of the glomerulus includes both the afferent and efferent arterioles. In addition, the relationship between these arterioles and the specialized portion of the distal nephron called the macula densa is illustrated. (Inset) The layers that comprise the filtration barrier are displayed. The outermost layer is composed of the visceral epithelial cells, the podocytes, next the glomerular basement membrane (GBM) and finally the fenestrated endothelial cells.

Figure 2.

Hydraulic and oncotic pressures along an idealized glomerular capillary and within Bowman’s space. The graph shows idealized hydraulic and oncotic pressure curves under conditions of filtration pressure equilibrium (curve A) when the mean net ultrafiltration pressure is equal to the shaded region between the and the curves. Curve B is a hypothetical linear profile of the oncotic pressure that would occur with a minimum value of the K_f. By contrast, in curve C, filtration equilibrium is never reached. Modified from Taal MW, Chertow GM, Marsden PA, Skorecki K, Yu ASL, Brenner BM: Brenner and Rector's The Kidney, 9th Ed., Philadelphia, Elsevier Saunders, 2012, with permission.

Figure 3.

The single nephron GFR (SNGFR) can be affected by alterations in each of the four major determinants of ultrafiltration. These affects can be expressed in a mathematical model, which helps illustrate the predicted effects of each change on the SNGFR. Normal values are indicated with a dotted line in each graph. Unless otherwise indicated in the graph, the input values are K_f = 0.095 nl/s·mmHg, = 35 mmHg, = 18 mmHg, and Q_A = 135 nl/min. (A) Alterations in K_f; (B) alterations in ; (C) alterations in ; (D) alterations in Q_A. Modified from Brenner BM, Dworkin LD, Ichikawa I: Glomerular filtration. In: Brenner and Rector’s The Kidney, 3rd Ed., edited by Brenner BM, Rector FC Jr, Philadelphia, Elsevier, 1986, with permission.

Figure 4.

The effects of graded reduction in renal artery perfusion pressure on glomerular hemodynamics in the rat. Glomerular blood flow (GBF) and glomerular capillary pressure remained relatively constant over the range of pressure from 80 to 120 mmHg, in response to a marked decrease in afferent arteriolar resistance (R_A). With further reduction in perfusion pressure to 60 mmHg, GBF declined proportionally more than primarily because of an increase in R_E. Reprinted from Taal MW, Chertow GM, Marsden PA, Skorecki K, Yu ASL, Brenner BM: Brenner and Rector’s The Kidney, 9th Ed., Philadelphia, Elsevier Saunders, 2012, with permission.

Figure 5.

Major molecular components of the podocyte and slit diaphragm. Interdigitating podocytes from neighboring cells form the elaborate slit diaphragm that is composed of nephrin. Podocin helps regulate trafficking of nephrin to the slit diaphragm. Proteins α-actinin-4 and INF2 play important roles in the maintenance of the actin cytoskeleton, whereas integrins help anchor the podocytes to the glomerular basement membrane. Mutations in α-actinin-4, INF2, and TRPC6 channel all cause autosomal dominant forms of FSGS. Mutations in nephrin and podocin cause recessive forms of steroid-resistant nephrosis.