Amyloidosis

Proteins play an important role in maintaining healthy body function. Normally proteins travel throughout the blood harmlessly to the muscles, bones, hair, and nails, however, some cells are capable of producing abnormal proteins. These abnormalities settle deep within the tissues and form disease causing deposits called amyloids, thus the diseases that result from these deposits are referred to as Amyloidosis. (1)

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What is Amyloidosis?

There are several different types of Amyloidosis that result from these abnormal protein deposits. The most prevalent forms of Amyloidosis, Primary Amyloidosis and Dialysis Related Amyloidosis, are both closely related to kidney disease. (1)

Primary Amyloidosis

This form of Amyloidosis occurs when the antibody producing cells are unable to operate properly which leads to an abnormal production of protein fibers made of antibody fragments. When these antibody fragments come together, they form harmful deposits in several organs, but primarily within the kidneys where the damage prohibits them from effectively removing urea and other wastes from the blood. The heart, lungs, brain, and digestive system are also targeted by these irregular amyloids. (1)

Symptoms

Those who suffer from Primary Amyloidosis may find that they also have the condition called proteinuria, where large amounts of protein are found within the urine, which usually signifies that the kidneys are not performing correctly. Others may also suffer from the condition known as multiple mylemoa. (1)

Treatment
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Renal Amyloidosis

In most cases, it is the discovery of proteinuria that motivates a physician to perform a biopsy to test for the presence of Amyloidosis. When a form of Amyloidosis has been diagnosed, drug therapy with melphalan and prednisone, a cancer drug and anti-inflammatory steroid drug, are used in attempt to slow the amyloid deposit build up and slowing the growth of these abnormal protein producing cells. As with many chemotherapy treatments, these drugs have similar side effects, such as nausea, vomiting, hair loss, and fatigue. Another effective treatment method that is used is transplanting the patient's own blood stem cells in place of the damaged bone marrow. Melphalan is utilized again for this procedure and can create the same serious side effects, so those with heart issues are not considered for this treatment. (1)

Dialysis Related Amyloidosis (DRA)

This form of Amyloidosis occurs when patients are receiving dialysis and the small protein called beta-2-microglobulin builds up within the blood as a result of nonfunctioning kidneys. These small proteins have the ability to link onto each other creating large molecules the form deposits, creating discomfort, and damaging the surrounding tissues. Older adults who have been on hemodialysis for more than five years are more likely to acquire DRA, because the Hemodiaylsis membranes are unable to remove the complex beta-2-microglobulin proteins form the bloodstream, causing blood levels the elevate and form deposits in the bone , joints, and tendons. (1)

Symptoms
DRA results in pain, stiffness, and fluid in the joints, and patients frequently develop cysts, or hollow cavities, that can lead to bone fractures. Amyloid deposits also cause tears in ligaments and tendons which leads to carpal tunnel syndrome, a very treatable condition resulting in the proteinAmyloidosis_and_Kidney_Disease_clip_image001.jpg buildup of the wrists. (1)

General Sympoms

  • Fatigue
  • Unexplained weight loss
  • Anemia (low level of red blood cells)
  • Weak hand grip
  • Skin changes
  • Clay-colored stools
  • Joint pain
  • Aarrhythmia (irregular heart beat)
  • Goiters of the thyroid gland (2)

Diagnosis

A biopsy is the only way to diagnose Amyloidosis with certainty, but imaging tests are used to evaluate damage done to the internal organs. Biopsies are taken from the liver, nerves, heart, or kidneys, and analyzed by a pathologist. (2)

Treatment

No cure for DRA has been found, although it can be treated several ways. A combination of steroids and chemotherapy drugs have been effective in targeting growth of abnormal plasma cells. Some drugs utalized include chlorambucil (Leukeran), melphalan (Alkeran), cyclophosphamide, Neosar, lenolidamide (Revlimid) and bortezomib (Velcade). Side effects can include nausea, vomiting, anemia, and fatigue. Immunotheraphy involving the injection of alpha interferon under the skin is another option to relieve the symptoms of Amyloidosis. Surgery is sometimes used to transplant affected organs, and liver transplants are usually successful. (2)

Possible Causes

  • Tuberculosis
  • Chronic inflammatory disorders
  • Rheumatoid arthritis
  • Autoimmune diseases
  • Familial visceral amyloidosis, Ostertag type
  • Renal dialysis
  • Finnish type amyloidosis
  • Still's Disease, Juvenile-Onset (3)

Risk Factors

No specific cause leads directly to the formation of the disease Amyloidosis, however, those who are above the age of forty are at a greater risk to develop Amyloidosis. More men are diagnosed than women, and 10% -15% of those who have multiple myeloma will develop Amyloidosis. Family history also has some effect, and may be attributed to a genetic mutation that has been passed down through the generations. (2)

Research

Progress in Amyoidosis research is ongoing. New combinations of steroids and chemotherapy drugs as well as stem cell transplantation are being explored in clinical trials and medical centers. (2)

Statistics

  • The prevalence rate is approx 1 in 90,666 or 0.00% or 3,000 people in USA
  • Less than 15% of patients display the physical characteristics typically associated with amyloidosis i.e. enlargement of tongue, submandibular, swelling, and facial purpura in the US
  • In 33-40% of amyloidosis patients, the kidney is affected in the US In 33-40% of amyloidosis patients, the kidney is affected in the US (4)
  • 1 in 6 amyloid patients have symptomatic liver involvement in the US (4)
  • There is congestive heart failure due to amyloidosis in about 20% of patients in the US (4)
  • 13% mortality rate for amyloidosis patients 100 days after treatment with melphalan and stem-cell transplantation(4)
  • 1 year is the median survival rate for patients who have a liver biopsy to treat amyloidosis in the US (4)
  • There were 941 deaths associated with Amyloidosis in the United States in 2004 (5)

Foundations

Amyloidosis Foundation
Amyloidosis Research Foundation
National Kidney Foundation

Works Cited
(1) http://kidney.niddk.nih.gov/kudiseases/pubs/Amyloidosis/#primary
(2) http://www.cancer.net/patient/Cancer+Types/Amyloidosis
(3) http://www.wrongdiagnosis.com/a/amyloidosis/causes.htm#whatcauses
(4) http://www.wrongdiagnosis.com/a/amyloidosis/stats.htm#medical_stats
(5) http://www.nationmaster.com/graph/mor_amy-mortality-amyloidosis
Picture 1 http://ocw.tufts.edu/data/51/551163/551177_xlarge.jpg
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Picture 3 http://www.kidneyurology.org/Library/Kidney_Health/Amyloidosis_and_Kidney_Disease_clip_image001.jpg