Amyloidosis and Kidney Disease
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Proteins are important building
blocks for all body parts, including
muscles, bones, hair, and nails.
Proteins circulate throughout the body
in the blood and are normally harmless.
Occasionally, cells produce abnormal
proteins that can settle in body tissue,
forming deposits and causing disease.
When these deposits of abnormal proteins
were first discovered, they were called
amyloid, and the disease process
amyloidosis.
In recent years, researchers have
discovered that different kinds of
proteins can form amyloid deposits and
have identified several types of
amyloidosis. Two of these types are
closely related to kidney disease. In
primary amyloidosis,
abnormal protein production occurs as a
first step and can lead to kidney
disease.
Dialysis-related amyloidosis (DRA),
on the other hand, is a result of kidney
disease.
Primary Amyloidosis
Primary amyloidosis occurs when the
body's antibody-producing cells do not
function properly and produce abnormal
protein fibers made of antibody
fragments. Some people with primary
amyloidosis have a condition called
multiple myeloma. The antibody fragments
come together to form amyloid deposits
in different organs, including the
kidneys, where they cause serious
damage. Injured kidneys can't function
effectively and may be unable to remove
urea and other wastes from the blood.
Elevated levels of these protein fibers
can also damage the heart, lungs, brain,
and digestive system.
One common sign of kidney amyloidosis
is the presence of abnormally high
levels of protein in the urine, a
condition known as
proteinuria. Healthy kidneys
prevent protein from entering the urine,
so the presence of protein may be a sign
that the kidneys aren't working
properly. A physician who finds large
amounts of protein in the urine may also
perform a biopsy?take a small sample of
tissue for examination with a
microscope?to confirm amyloidosis.
Current treatments are aimed at
slowing the progression of amyloid
build-up. Combination drug therapy with
melphalan, a cancer drug, and
prednisone, an anti-inflammatory steroid
drug, may improve organ function and
survival rates by interrupting the
growth of the abnormal cells that
produce amyloid protein. These are the
same drugs used in chemotherapy to treat
certain cancers, such as multiple
myeloma, and they may have serious side
effects, such as nausea and vomiting,
hair loss, and fatigue.
Some clinics have reported promising
results treating amyloidosis by
transplanting the patient?s own blood
stem cells to replace diseased or
damaged bone marrow. The therapy also
requires high doses of melphalan, so
side effects can be serious. Patients
with heart problems may not be
considered for this treatment.
Dialysis-Related Amyloidosis
Normal kidneys filter and remove
excess small proteins from the blood,
thus keeping blood levels normal. When
the kidneys don't work properly, as in
patients receiving dialysis, one type of
small protein calle
beta-2-microglobulin builds
up in the blood. When this occurs,
beta-2-microglobulin molecules may join
together, like the links of a chain,
forming a few very large molecules from
many smaller ones. These large molecules
can form deposits and eventually damage
the surrounding tissues and cause great
discomfort. This condition is called
dialysis-related amyloidosis (DRA).
DRA is relatively common in patients,
especially older adults, who have been
on hemodialysis for more than 5 years.
Hemodialysis membranes that have been
used for many years don't effectively
remove the large, complex
beta-2-microglobulin proteins from the
bloodstream. Newer hemodialysis
membranes, as well as peritoneal
dialysis, remove beta-2-microglobulin
more effectively, but not enough to keep
blood levels normal. As a result, blood
levels remain elevated, and deposits
form in bone, joints, and tendons (the
tissue that connects the muscle to the
bone). DRA may result in pain,
stiffness, and fluid in the joints.
Patients with DRA may also develop
hollow cavities, or cysts, in some of
their bones; these may lead to
unexpected bone fractures. Amyloid
deposits may cause tears in ligaments
and tendons. Most patients with these
problems can be helped by surgical
intervention.
Half of the people with DRA also
develop a condition called carpal tunnel
syndrome, which results from the unusual
buildup of protein in the wrists.
Patients with this condition may
experience numbness or tingling,
sometimes associated with muscle
weakness, in their fingers and hands.
This is a treatable condition.
Amyloid may build up in the wrist and
cause bone
cysts or carpal tunnel syndrome.
Unfortunately, no cure for DRA has
been found, although a successful kidney
transplant may stop the disease from
progressing. However, DRA has caught the
attention of dialysis engineers, who are
attempting to develop new dialysis
membranes that can remove larger amounts
of beta-2-microglobulin from the blood.
