C h a p t e r 2 5
Disorders of Renal Function
623
Types of Glomerular Disease
The clinical manifestations of glomerular disorders gener-
ally fall into several categories: acute nephritic syndromes,
rapidly progressive glomerulonephritis, nephrotic syn-
drome, IgA nephropathy, hereditary nephritis (e.g., Alport
syndrome), and chronic glomerulonephritis.
4,5,10–13
The
nephritic syndromes produce a proliferative inflamma-
tory response, whereas the nephrotic syndrome produces
increased permeability of the glomerulus. Because most
glomerular disorders can produce mixed nephritic and
nephrotic syndromes, a definitive diagnosis often requires
renal biopsy.
Many cases of glomerular disease result in mild
asymptomatic illness that is not recognized or is brought
to the attention of a health care professional during
routine screening or physical examination for another
purpose. Disorders such as IgA nephropathy and Alport
syndrome often present with asymptomatic hematuria
and/or proteinuria.
Acute Nephritic Syndrome
Acute nephritic syndrome is an acute inflammatory
process that occludes the glomerular capillary lumen
and damages the capillary wall. It may occur as a renal-limited primary disorder, such as acute postinfectious
glomerulonephritis, or as a secondary complicating dis-
order in systemic diseases, such as SLE. In its most dra-
matic form, acute nephritic syndrome is characterized by
sudden onset of hematuria (either microscopic or grossly
visible, with red cell casts), variable degrees of protein-
uria, diminished glomerular filtration rate (GFR), oligu-
ria, and signs of impaired renal function. Extracellular
fluid accumulation, edema, and hypertension develop
because of the decreased GFR and enhanced tubular
reabsorption of salt and water.
Acute Postinfectious Glomerulonephritis.
Acute
postinfectious glomerulonephritis usually occurs after
infection with certain strains of group A
β
-hemolytic
streptococci and is caused by deposition of immune
complexes.
4,5,10,14
It also may occur after infections by
other organisms, including staphylococci and a number
of viral agents, such as those responsible for mumps,
measles, and chickenpox.
4
This type of glomerular dis-
ease is now rare in industrialized nations, but continues
to be a common disorder in the underprivileged popula-
tions of the world.
5
Although the disease is seen primar-
ily in children, persons of any age can be affected.
The acute phase of postinfectious glomerulonephri-
tis is characterized by diffuse glomerular enlargement
and hypercellularity. The hypercellularity is caused by
infiltration of leukocytes, both neutrophils and mono-
cytes; proliferation of endothelial and mesangial cells;
and formation of electron-dense subepithelial depos-
its, often having the appearance of “humps” (see Fig.
25-4B). There is also swelling of the endothelial cells,
and the combination of proliferation, swelling, and
leukocyte infiltration obliterates the glomerular capil-
lary lumens. On immunofluorescence microscopy there
are granular deposits of immunoglobulin G (IgG) and
the complement component C3 in the mesangium and
along the basement membrane (Fig. 25-6).
The classic case of poststreptococcal glomerulonephri-
tis follows a streptococcal infection by approximately
7 to 12 days—the time needed for the development of
antibodies. The primary infection usually involves the
pharynx (pharyngitis), but can also result from a skin
infection (impetigo). Oliguria, which develops as the
GFR decreases, is one of the first symptoms. Proteinuria
and hematuria follow because of increased glomeru-
lar capillary wall permeability. The red blood cells are
degraded by materials in the urine, and cola-colored
urine may be the first sign of the disorder. Sodium and
water retention gives rise to edema (particularly of the
face and hands) and hypertension. Important laboratory
findings include an elevated antistreptococcal antibody
(ASO) titer, a decline in serum concentrations of C3 and
other components of the complement cascade, and cryo-
globulins (i.e., large immune complexes) in the serum.
Treatment of acute poststreptococcal glomerulone-
phritis includes eliminating the streptococcal infection
with antibiotics and providing supportive care. The dis-
order generally carries an excellent prognosis and rarely
causes chronic kidney disease. In children, spontane-
ous resolution of the glomerular lesion and nephritic
syndrome is usually the norm and occurs within 6 to
8 weeks. Adults tend to recover more slowly, often with
some degree of persistent azotemia that may, in some
cases, progress to chronic kidney disease.
Rapidly Progressive Glomerulonephritis
Rapidly progressive glomerulonephritis is a clinical syn-
drome characterized by signs of severe glomerular injury
that does not have a specific cause. As its name indicates,
this type of glomerulonephritis is rapidly progressive,
FIGURE 25-6.
Acute postinfectious glomerulonephritis. An
immunofluorescence micrograph demonstrates granular
staining for complement C3 in capillary walls and the
mesangium. (From Jennette JC.The kidney. In: Rubin R,
Strayer DS, eds. Rubin’s Pathology: Clinicopathologic
Foundations of Medicine. 6th ed. Philadelphia, PA: Wolters
Kluwer Health | Lippincott Williams &Wilkins; 2012:776.)
