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U N I T 7
Kidney and Urinary Tract Function
often within a matter of months. The disorder involves
focal and segmental proliferation of glomerular cells and
recruitment of monocytes and macrophages with the for-
mation of crescent structures that obliterate the Bowman
space.
5
Rapidly proliferative glomerulonephritis may be
caused by a number of immunologic disorders, some sys-
temic and others restricted to the kidney. Among the dis-
eases associated with this form of glomerulonephritis are
immune complex disorders such as SLE, and an aggres-
sive form of glomerulonephritis called
Goodpasture
syndrome.
Goodpasture Syndrome.
An uncommon and aggres-
sive form of glomerulonephritis, Goodpasture syndrome
is caused by antibodies to the glomerular basement
membrane (GBM). The anti–glomerular membrane
(anti-GBM) antibodies cross-react with the pulmonary
alveolar basement membrane to produce the syndrome
of pulmonary hemorrhage associated with renal failure.
The pathologic hallmark of anti-GBM glomerulone-
phritis is diffuse linear staining of glomerular basement
membranes for IgG (Fig. 25-7). The cause of the disor-
der is unknown, although influenza infection and expo-
sure to hydrocarbon solvent (found in paints and dyes)
have been implicated in some persons, as have various
drugs and cancers. There is a high prevalence of certain
human leukocyte antigen subtypes (e.g., HLA-DRB1)
in those affected, suggesting a genetic predisposition.
4
Treatment includes plasmapheresis to remove circu-
lating anti-GBM antibodies and immunosuppressive
therapy (i.e., corticosteroids and cyclophosphamide) to
inhibit antibody production.
Nephrotic Syndrome
The nephrotic syndrome is characterized by massive pro-
teinuria (
≥
3.5 g/day in adults) and lipiduria (e.g., free
fat, oval bodies, fatty casts), along with an associated
hypoalbuminemia (<3 g/dL), generalized edema, and
hyperlipidemia.
4,5,10
The nephrotic syndrome is not a
specific glomerular disease, but a constellation of clini-
cal findings that result from an increase in glomerular
permeability and loss of plasma proteins in the urine
(Fig. 25-8).
The glomerular membrane acts as a size-specific bar-
rier through which the glomerular filtrate must pass. An
increase in permeability allows proteins to escape from
the plasma into the glomerular filtrate, often leading to an
excessive loss of albumin—the smallest and most abun-
dant of the plasma proteins. Generalized edema, which
is a hallmark of the nephrotic syndrome, results from a
decrease in the plasma colloidal osmotic pressure due to
the hypoalbuminemia that develops as albumin is lost
from the vascular compartment (see Chapter 8). There
is also salt and water retention, which aggravates the
edema. Initially, the edema presents in dependent parts
of the body such as the lower extremities, but becomes
more generalized as the disease progresses (Fig. 25-9).
Dyspnea due to pulmonary edema, pleural effusions, and
diaphragmatic compromise due to ascites can develop in
persons with nephrotic syndrome.
The hyperlipidemia that occurs in persons with ne-
phrosis is characterized by elevated levels of triglyc-
erides and low-density lipoproteins (LDLs). Levels of
high-density lipoproteins (HDLs) usually are normal. It
is thought that these abnormalities are related, at least in
part, to increased synthesis of lipoproteins in the liver sec-
ondary to a compensatory increase in albumin produc-
tion.
13
Because of the elevated LDL levels, persons with
nephrotic syndrome are at increased risk for development
of atherosclerosis.
FIGURE 25-7.
Anti–glomerular basement membrane
glomerulonephritis. Linear immunofluorescence for IgG
is seen along the glomerular basement membrane. (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; 2012:782.)
Glomerular damage
Increased permeability to proteins
Proteinuria ( 3.5 g/24 h)
Hypoproteinemia
Edema
Hyperlipidemia
Compensatory synthesis
of proteins by liver
Decreased plasma
oncotic pressure
FIGURE 25-8.
Pathophysiology of the nephrotic syndrome.
