626
U N I T 7
Kidney and Urinary Tract Function
Focal segmental glomerulosclerosis can be viewed
as a heterogeneous group of glomerular diseases with
different causes, pathologies, and outcomes. The dis-
order may be idiopathic (primary) or occur secondary
to reduced oxygen in the blood (e.g., sickle cell disease
and cyanotic congenital heart disease), human immu-
nodeficiency virus (HIV) infection, or intravenous drug
abuse.
4,5
It can also occur as a secondary event reflecting
scarring from other glomerular disorders, such as IgA
nephropathy. There is also evidence of a genetic basis
for some cases of the disorder. Multiple factors probably
lead to a common pathway of injury.
Clinical presentations and outcomes vary among the
different patterns of injury. Most people with the disor-
der show persistent proteinuria and progressive decline
in renal function. Many persons with the disorder prog-
ress to kidney failure within 5 to 20 years.
5
The disorder
usually is treated with corticosteroids. Although kidney
transplantation is the preferred treatment for end-stage
kidney disease, focal segmental glomerulonephritis
occurs in half of these people.
IgA Nephropathy
IgA nephropathy (i.e., Berger disease) is a primary glo-
merulonephritis characterized by the presence of glo-
merular IgA immune complex deposits. It can occur at
any age, but most commonly has its onset in the sec-
ond and third decades of life.
4,5,10,16,17
The disease occurs
more commonly in men than women and is the most
common cause of glomerular nephritis in Asians.
The disorder is characterized by the deposition of
IgA-containing immune complexes in the mesangium
of the glomerulus (Fig. 25-10). Once deposited in the
kidney, the immune complexes are associated with
glomerular inflammation. The cause of the disorder is
unknown. Some people with the disorder have elevated
serum IgA levels. Recent studies have focused on poten-
tial abnormalities of the IgA molecule as a factor in the
pathogenesis of the disorder.
16
Early in the disease, many people with the disorder
have no obvious symptoms and the disorder is dis-
covered during routine screening or examination for
another condition. In others, the disorder presents with
gross hematuria that is preceded by upper respiratory
tract infection, gastrointestinal tract symptoms, or a
flulike illness. The hematuria usually lasts 2 to 6 days.
Approximately one half of those with gross hematuria
have a single episode, whereas the remainder experience
a gradual progression of the disease with recurrent epi-
sodes of hematuria and mild proteinuria. Progression
usually is slow, extending over several decades.
Immunofluorescence microscopy, using a specimen
obtained through renal biopsy, is essential for diagnosis
of IgA nephropathy.
5
The diagnostic finding is mesangial
staining for IgA that is more intense than staining for
IgG or IgM. At present, there are no satisfactory treat-
ment measures for IgA nephropathy. The role of immu-
nosuppressive drugs such as steroids and cytotoxic drugs
is not clear.
Hereditary Nephritis (Alport Syndrome)
Alport syndrome represents a hereditary defect of the glo-
merular basement membrane that results in hematuria and
may progress to chronic renal failure.
4,5
Approximately
85% of cases are inherited as an X-linked autosomal
dominant trait, whereas others have autosomal dominant
and recessive patterns of inheritance.
5
In X-linked pedi-
grees, boys are usually affected more seriously than girls.
Affected boys usually progress to renal failure as adults,
but progression may occur during adolescence. Although
many girls never have more than mild hematuria with or
without mild proteinuria, some have more significant dis-
ease and may even progress to kidney failure.
Diagnosis of Alport syndrome is often made after
examination of the urine of a child from a family with
multiple cases of hereditary nephritis. Children may ini-
tially present with heavy microscopic hematuria (large
amount of blood on dipstick), followed by the devel-
opment of proteinuria. Many, but not all, persons with
Alport syndrome have sensorineural deafness and vari-
ous eye disorders, including lens dislocation, posterior
cataracts, and corneal dystrophy. The hearing loss is
bilateral and often is first detected during adolescence.
Chronic Glomerulonephritis
Chronic glomerulonephritis represents the chronic phase
of a number of specific types of glomerulonephritis.
4,5
Some forms of acute glomerulonephritis (e.g., poststrep-
tococcal glomerulonephritis) undergo complete resolu-
tion, whereas others progress at variable rates to chronic
glomerulonephritis. Some persons who present with
chronic glomerulonephritis have no history of glomeru-
lar disease. These cases may represent the end result of
relatively asymptomatic forms of glomerulonephritis.
Histologically, the condition is characterized by small
kidneys with sclerosed glomeruli. In most cases, chronic
glomerulonephritis develops insidiously and slowly pro-
gresses to chronic kidney disease over a period of years
(see Chapter 26).
FIGURE 25-10.
IgA nephropathy. An immunofluorescence
micrograph shows deposits of IgA in the mesangial areas.
(From Jennette JC.The kidney. In: Rubin R, Strayer D, eds.
Rubin’s Pathology: Clinicopathologic Foundations of Medicine.
6th ed. Philadelphia, PA: Wolters Kluwer Health | Lippincott
Williams &Wilkins; 2012:781.)
