Page 703 - Small Animal Internal Medicine, 6th Edition

CHAPTER 40
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Glomerular Disease

Glomerular disease is an important cause of chronic kidney endothelium is much more permeable to water and crystal-
disease (CKD) in humans and has been increasingly recog- loids than are systemic capillaries, and the negatively charged
nized in veterinary medicine. Destruction of the glomerulus endothelial surface contributes to the charge selectivity of
renders the remainder of the nephron nonfunctional, and the glomerular barrier. The GBM contains type IV collagen,
progressive destruction of glomeruli can lead to decreased proteoglycans, laminin, fibronectin, and water. The proteo-
glomerular filtration rate, azotemia, and renal failure. Impor- glycans are large, highly negatively charged molecules
tant glomerular diseases of dogs include glomerulonephritis consisting of a protein backbone with polysaccharide (gly-
(GN), glomerular amyloidosis, familial glomerular base- cosaminoglycan) side chains. These proteoglycans are
ment membrane (GBM) disorders, and glomerular sclerosis. responsible for the charge selectivity of the basement mem-
GN is less common in cats, and amyloidosis in cats affects brane. Type IV collagen in the GBM forms a mesh and
the renal medulla more severely than the glomeruli. contributes to the size selectivity of the glomerular capillary
Marked, persistent proteinuria is the hallmark of primary wall. The visceral epithelial cells or podocytes cover the fil-
glomerular disease. The term nephrotic syndrome tradition- tration barrier on the urinary side via primary and interdigi-
ally has been used to describe patients with proteinuria, tating secondary foot processes. The negatively charged cell
hypoalbuminemia, hypercholesterolemia, and edema or surface of the podocyte foot processes contributes to their
ascites. Many dogs and cats with glomerular disease, however, unique morphology and the charge selectivity of the glo-
do not have clinically detectable ascites at presentation. In merular barrier. The podocytes synthesize the GBM and may
one study of dogs with glomerular disease, nephrotic syn- phagocytize macromolecules trapped in the filtration barrier.
drome was not associated with specific histopathologic diag- The mesangial cells of the glomerulus provide structural
noses, but dogs with nephrotic syndrome had higher urine support for the capillary loops (Fig. 40.3). They produce
protein-to-creatinine (UPC) ratios and shorter survival mesangial matrix, similar to the basement membrane in
times than dogs with nonnephrotic glomerular disease. composition, and may clear filtration residues from the
Human patients excreting more than 3.5 g protein/1.73 m mesangial space by virtue of their phagocytic capacity. Their
2
2
body surface area/day (likely equivalent to 2 g/m in dogs) contractile elements can alter the amount of glomerular
in their urine or with UPC ratios > 2.0 to 3.5 are said to have surface area available for filtration in response to mediators
nephrotic-range proteinuria. such as angiotensin II. The mesangium is an early site of
deposition of immune complexes and amyloid fibrils, and
mesangial cells can contribute to inflammation and progres-
NORMAL STRUCTURE sion of CKD by the release of eicosanoids, cytokines, and
growth factors and by increased matrix production. Ulti-
The glomerulus is a unique vascular structure consisting of mately, these effects can lead to glomerular sclerosis.
a capillary bed between two arterioles (Fig. 40.1). The glo- The parietal epithelial cells line the urinary side of the
merular capillary wall is a size- and charge-selective barrier. glomerular capsule (Bowman’s capsule) and are continuous
It excludes macromolecules more than 35 Å in radius (serum with the visceral epithelial cells at the vascular pole of the
albumin has a molecular radius of 36 Å) and, for any given glomerulus and with the proximal tubule at the urinary pole
size, negatively charged macromolecules experience greater (see Fig. 40.1). The juxtaglomerular apparatus, at the vascu-
restriction to filtration than neutral macromolecules. lar pole, consists of specialized smooth muscle cells of the
The filtration barrier of the glomerulus consists of three afferent and efferent arterioles containing electron-dense
layers, from the vascular space to the urinary space—the renin granules, and the macula densa, a specialized segment
capillary endothelium, GBM, and interdigitating foot proc- of the distal tubule. The juxtaglomerular apparatus mediates
esses of the podocytes (Fig. 40.2). The fenestrated capillary tubuloglomerular feedback.

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