C h a p t e r 2 5
Disorders of Renal Function
619
autosomal recessive polycystic kidney disease, and neph-
ronophthisis and medullary cystic kidney diseases.
Autosomal Dominant Polycystic Kidney
Disease
Autosomal dominant (adult) polycystic kidney disease
(ADPKD) is the most common of all inherited kidney
diseases, with 600,000 to 700,000 cases in the United
States and about 12.5 million cases worldwide.
6
About
5000 to 6000 new cases are diagnosed in the United
States each year, about 40% before the age of 45.
6
About
5% to 10% of these persons develop chronic kidney dis-
ease that requires dialysis or kidney transplant.
5
The disorder is characterized by multiple expand-
ing cysts of both kidneys that ultimately destroy the
surrounding kidney structures and cause renal failure
(Fig. 25-2A). There are two genetic forms of ADPKD:
polycystin-1I which is caused by mutations in the
PKD1
gene and accounts for 85% of cases; and polycystin-2,
which is caused by mutations in the
PKD2
gene and
accounts for most of the remaining 15% of cases.
4–8
Although the two mutations produce almost identical
renal and extrarenal disease, disease progression is typi-
cally more rapid in people with the
PKD1
gene.
Recent research suggests that the products of the
polycystin genes are transmembrane proteins found on
the primary cilia that line the apical surface of the tubu-
lar epithelial cells of the kidney. Because the cilia proj-
ect out and above the tubular cell surface like antennas,
they are currently thought to act as sensors of urinary
flow and as signal transducers for tubular cell prolifera-
tion, differentiation, and apoptosis.
9
The polycystin genes
also regulate vascular development in other organs such
as the liver, brain, and pancreas, accounting for the extra-
renal manifestations that often accompany the disorder.
In ADPKD, cysts in the kidney increase in size over
time, ultimately destroying normal renal tissue. The kid-
neys are usually enlarged and may achieve enormous
sizes (Fig. 25-3). The external contours of the kidneys
are distorted by numerous cysts, some as large as 5 cm
in diameter, filled with straw-colored fluid.
5
Cysts also
may be found in the liver and, less commonly, the pan-
creas and spleen. Hepatic cysts, which occur in one third
of persons with ADPKD, are generally asymptomatic
and liver function is normal.
5
Mitral valve prolapse and
other valvular abnormalities are found in 20% to 25%
of people, but most are asymptomatic. One of the most
devastating extrarenal manifestations is a weakness in
the walls of the cerebral arteries that can lead to aneu-
rysm formation. It has been estimated that persons with
ADPKD who have a family member with ADPKD and
a history of intracranial aneurysm or cerebral hemor-
rhage have a 20% chance of developing an intracranial
aneurysm.
6
The manifestations of ADPKD include pain from
the enlarging cysts that may reach debilitating levels,
episodes of gross hematuria from bleeding into a cyst,
infected cysts from ascending UTIs, and hypertension
resulting from compression of intrarenal blood vessels
with activation of the renin-angiotensin mechanism.
4,5
Renal colic caused by nephrolithiasis, or kidney stones,
occurs in about 20% of persons with ADPKD.
6
The
progress of the disease is slow, and chronic kidney dis-
ease is uncommon before 40 years of age.
Ultrasonography usually is the preferred technique
for the diagnosis of ADPKD in symptomatic patients
and for screening of asymptomatic family members.
Computed tomography (CT) may be used for detection
of small cysts. Genetic linkage studies are now available
Cyst formation in
autosomal dominant
polycystic kidney disease
Cyst formation in
autosomal recessive
polycystic kidney disease
A
B
FIGURE 25-2.
Mechanism of cyst formation in polycystic
kidney disease.
(A)
In autosomal dominant polycystic kidney
disease, cystic outpouchings arise in every tubule segment
and rapidly close off the nephron of origin.
(B)
In autosomal
recessive polycystic kidney disease, cysts are derived from
collecting tubules, which remain connected to the nephron of
origin. (FromWilson PD. Polycystic kidney disease. N Engl J
Med. 2004;350:155. Copyright © 2004. Massachusetts Medical
Society.)
FIGURE 25-3.
Gross pathology of polycystic kidneys. (From
the Centers for Disease Control and Prevention Public Health
Images Library. No. 861. Courtesy of Edwin P. Ewing, Jr).
