Introduction to Glomerular Diseases

The kidneys lie in the retroperitoneal space slightly above the level of the umbilicus. They range in length and weight, respectively, from approximately 6 cm and 24 g in a full-term newborn to ≥12 cm and 150 g in an adult. The kidney (see Fig. 502-1 on the Nelson Textbook of Pediatrics website at www.expertconsult.com) has an outer layer, the cortex, which contains the glomeruli, proximal and distal convoluted tubules, and collecting ducts; and an inner layer, the medulla, that contains the straight portions of the tubules, the loops of Henle, the vasa recta, and the terminal collecting ducts (see Fig. 502-2 on the Nelson Textbook of Pediatrics website at www.expertconsult.com).

Figure 502-1 Gross morphology of the renal circulation.

(From Pitts RF: Physiology of the kidney and body fluids, ed 3, Chicago, 1974, Year Book Medical Publishers.)

Figure 502-2 Comparison of the blood supplies of cortical and juxtamedullary nephrons.

(From Pitts RF: Physiology of the kidney and body fluids, ed 3, Chicago, 1974, Year Book Medical Publishers.)

The blood supply to each kidney usually consists of a main renal artery that arises from the aorta; multiple renal arteries can occur. The main artery divides into segmental branches within the medulla, becoming the interlobar arteries that pass through the medulla to the corticomedullary junction. At this point, the interlobar arteries branch to form the arcuate arteries, which run parallel to the surface of the kidney. Interlobular arteries originate from the arcuate arteries and give rise to the afferent arterioles of the glomeruli. Specialized muscle cells in the wall of the afferent arteriole and specialized distal tubular cells adjacent to the glomerulus (macula densa) form the juxtaglomerular apparatus that controls the secretion of renin. The afferent arteriole divides into the glomerular capillary network, which then recombines into the efferent arteriole (Fig. 502-2). The juxtamedullary efferent arterioles are larger than those in the outer cortex and provide the blood supply, as the vasa recta, to the tubules and medulla.

Each kidney contains approximately 1 million nephrons (glomeruli and associated tubules). There is a large distribution of “normal nephron number” in humans, with the mean ±2 standard deviations (SD) ranging from 200,000 to 2 million nephrons/kidney. This variation can have major pathophysiologic significance as a risk factor for the later development of hypertension and progressive renal dysfunction. In humans, formation of nephrons is complete at 36-40 wk of gestation, but functional maturation with tubular growth and elongation continues during the 1st decade of life. Because new nephrons cannot be formed after birth, any disease that results in progressive loss of nephrons can lead to renal insufficiency. A decreased number of nephrons secondary to low birth weight, prematurity, and/or unknown genetic or environmental factors is hypothesized to be a risk factor for the development of primary hypertension and progressive renal dysfunction in adulthood. Low nephron number presumably results in hyperfiltration and eventual sclerosis of “overworked” nephron units.

The glomerular network of specialized capillaries serves as the filtering mechanism of the kidney. The glomerular capillaries are lined by endothelial cells (Fig. 502-3) and have very thin cytoplasm that contains many holes (fenestrations). The glomerular basement membrane (GBM) forms a continuous layer between the endothelial and mesangial cells on one side and the epithelial cells on the other. The membrane has 3 layers: (1) a central electron-dense lamina densa; (2) the lamina rara interna, which lies between the lamina densa and the endothelial cells; and (3) the lamina rara externa, which lies between the lamina densa and the epithelial cells. The visceral epithelial cells cover the capillary and project cytoplasmic foot processes, which attach to the lamina rara externa. Between the foot processes are spaces or filtration slits. The mesangium (mesangial cells and matrix) lies between the glomerular capillaries on the endothelial cell side of the GBM and forms the medial part of the capillary wall. The mesangium may serve as a supporting structure for the glomerular capillaries and probably has a role in the regulation of glomerular blood flow, filtration, and the removal of macromolecules (such as immune complexes) from the glomerulus. Bowman’s capsule, which surrounds the glomerulus, is composed of a basement membrane, which is continuous with the basement membranes of the glomerular capillaries and the proximal tubules, and the parietal epithelial cells, which are contiguous with the visceral epithelium (Fig. 502-4).

Figure 502-3 Electron micrograph of the normal glomerular capillary (Cap) wall demonstrating the endothelium (En) with its fenestrations (f), the glomerular basement membrane (B) with its central dense layer, the lamina densa (LD), and adjoining lamina rara interna (LRI) and externa (LRE) (long arrow) and the epithelial cell foot processes (fp) with their thick cell coat (c). The glomerular filtrate passes through the endothelial fenestrae, crosses the basement membrane, and passes through the filtration slits (short arrow) between the epithelial cell foot processes to reach the urinary space (US) (×60,000). J is the junction between two endothelial cells.

(From Farquhar MG, Kanwar YS: Functional organization of the glomerulus: state of the science in 1979. In Cummings NB, Michael AF, Wilson CB, editors: Immune mechanisms in renal disease, New York, 1982, Plenum.)

Figure 502-4 Schematic depiction of the glomerulus and surrounding structures.

As the blood passes through the glomerular capillaries, the plasma is filtered through the glomerular capillary walls. The ultrafiltrate, which is cell free, contains all of the substances in plasma (electrolytes, glucose, phosphate, urea, creatinine, peptides, low molecular weight proteins) except proteins having a molecular weight of ≥68 kd (such as albumin and globulins). The filtrate is collected in Bowman’s space and enters the tubules, where its composition is modified by tightly regulated secretion and absorption of solute and fluid, until it leaves the kidney as urine.