C h a p t e r 2 5
Disorders of Renal Function
625
The largest proportion of protein lost in the urine
is albumin, but globulins also may be lost. As a result,
persons with nephrosis are often vulnerable to infec-
tions, particularly those caused by staphylococci and
pneumococci.
4
This decreased resistance to infection
probably is related to the loss of both immunoglobulins
and low–molecular-weight complement components in
the urine. Many binding proteins also are lost in the
urine. Consequently, the plasma levels of many ions
(iron, copper, zinc) and hormones (thyroid and sex hor-
mones) may be low. Many drugs require protein binding
for transport. Hypoalbuminemia reduces the number
of available protein-binding sites, thereby producing a
potential increase in the amount of free (active) drug
that is available.
Persons with nephrotic syndrome are also at risk for
thrombotic complications. These complications reflect
a disruption in the function of the coagulation system
brought about by a loss of coagulation and anticoagula-
tion factors in the urine. Renal vein thrombosis, once
thought to be a cause of the disorder, is more likely a
consequence of the hypercoagulable state. Other throm-
botic complications include deep vein thrombosis and
pulmonary emboli.
The glomerular derangements that occur with nephro-
sis can develop as a primary disorder or secondary
to changes caused by systemic diseases such as diabe-
tes mellitus and SLE.
4,5
Among the primary glomerular
lesions leading to nephrotic syndrome are minimal-change
disease (lipoid nephrosis), focal segmental glomerulo-
sclerosis, and membranous glomerulonephritis. The rela-
tive frequency of these causes varies with age. In children
younger than 15 years of age, nephrotic syndrome almost
always is caused by primary idiopathic glomerular dis-
ease, whereas in adults it often is a secondary disorder.
4
Minimal-Change Disease (Lipoid Nephrosis).
Minimal-
change disease is characterized by diffuse loss (through
fusion) of the podocytes or foot processes of the visceral
epithelial cells of the glomeruli. It is most commonly seen
in children (peak incidence at 2 to 6 years of age),
5
but
may occasionally occur in adults. Although the cause of
minimal-change disease is unknown; children in whom
the disease develops often have a history of recent upper
respiratory infections or of receiving routine childhood
immunizations.
4
Minimal-change disease does not usu-
ally progress to renal failure, but can cause significant
complications, including predisposition to infection
with gram-positive organisms, tendency toward throm-
boembolic events, hyperlipidemia, and protein malnu-
trition. The prognosis in children with the disorder is
good; more than 90% respond to a short course of glu-
cocorticoids. Adults also respond to corticosteroids, but
the response is slower.
4
Membranous Glomerulonephritis.
Membranous glo-
merulonephritis is the most common cause of primary
nephrosis in adults.
5,10,11
The disorder is caused by diffuse
thickening of the glomerular basement membrane due
to deposition of immune complexes. The disorder may
be idiopathic or associated with a number of disorders,
including autoimmune diseases such as SLE, infections
such as chronic hepatitis B, metabolic disorders such as
diabetes mellitus and thyroiditis, and use of certain drugs
such as gold compounds, penicillamine, and captopril.
5
The disorder usually begins with an insidious onset
of the nephrotic syndrome with peripheral edema,
hypoalbuminemia, and hyperlipidemia or, in a small
percentage of patients, with nonnephrotic proteinuria.
Hematuria and mild hypertension may be present. The
progress of the disease is variable, with less than 40%
eventually developing renal insufficiency. Spontaneous
remissions and a relatively benign outcome occur more
commonly in women and those with proteinuria in the
nonnephrotic range. Treatment is controversial. Because
of the variable course of the disease, the overall effec-
tiveness of corticosteroids and other immunosuppres-
sive therapy in controlling the progress of the disease
has been difficult to evaluate.
5,10
Focal Segmental Glomerulosclerosis.
Focal segmen-
tal glomerulosclerosis (FSGS) is characterized by scle-
rosis (i.e., increased collagen deposition) in some but
not all glomeruli. Moreover, in the affected glomeruli,
only a portion of the glomerular tuft is involved.
4,5,10,11,15
Focal segmental glomerulosclerosis causes 30% of pri-
mary nephrotic syndrome in adults and 10% in chil-
dren. It is more common in blacks than whites and is the
leading cause of primary nephrotic syndrome in African
Americans.
5
FIGURE 25-9.
Photo of an African child with nephrosis
associated with malaria. (From the Centers for Disease Control
and Prevention Public Health Images Library. No. 3894.
Courtesy of Myron Schultz.)
