Amyloidosis and


Kidney Disease
 

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 

National Institute of Diabetes and Digestive and Kidney Diseases 

NATIONAL INSTITUTES OF HEALTH 

U.S. Department of Health 

and Human Services 
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 called 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. 

Amyloid may build up in the wrist and cause bone cysts or 

carpal tunnel syndrome. 

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. 

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. 

2 
Hope Through Research 

In recent years, researchers have learned a 

great deal about kidney disease. The National 

Institute of Diabetes and Digestive and Kidney 

Diseases (NIDDK) sponsors several programs 

aimed at understanding kidney failure and 

finding treatments to stop its progression. 

The NIDDK’s Division of Kidney, Urologic, 

and Hematologic Diseases supports basic 

research into normal kidney function and the 

diseases that impair normal function at the 

cellular and molecular levels, including 

amyloidosis. Recently, NIDDK-sponsored 

researchers have identified several genes that 

may contribute to a hereditary form of primary amyloidosis. In 2001, a team of researchers 

at the Indiana University School of Medicine 

located a mutation in the apolipoprotein A-II 

gene of a patient with kidney damage caused 

by amyloidosis. The researchers noted that 

the patient had reabsorbed most of the amyloid. They theorize that learning how this 

reabsorption occurs may point the way to 

possible therapies for all forms of amyloidosis. 

The NIDDK is also supporting multiple efforts 

to develop a blood detoxification system 

that will eliminate beta-2-microglobulin. 

For More Information 

National Institute of Arthritis and 

Musculoskeletal and Skin Diseases 

National Institutes of Health 

1 AMS Circle 

Bethesda, MD 20892–3675 

Phone: 1–877–226–4267 or 301–495–4484 

TTY: 301–565–2966 

Fax: 301–718–6366 

Email: niamsinfo@mail.nih.gov 

Internet: www.niams.nih.gov 

Amyloidosis Support Network 

1490 Herndon Lane 

Marietta, GA 30062 

Phone: 1–888–AMYLOID (269–5643) 

or 713–466–4351 

Support group information: 

800–689–1238 x27 

Email: info@amyloidosis.org 

Internet: amyloidosis.org 

About the Kidney Failure Series 

The NIDDK Kidney Failure Series includes six 

booklets and seven fact sheets that can help 

you learn more about treatment methods for 

kidney failure, complications of dialysis, financial help for the treatment of kidney failure, 

and eating right on hemodialysis. For free 

single printed copies of this series, please 

contact the National Kidney and Urologic 

Diseases Information Clearinghouse. 

3 
National Kidney and Urologic 

Diseases Information Clearinghouse 

3 Information Way 

Bethesda, MD 20892–3580 

Phone: 1–800–891–5390 

Fax: 703–738–4929 

Email: nkudic@info.niddk.nih.gov 

Internet: www.kidney.niddk.nih.gov 

The National Kidney and Urologic Diseases 

Information Clearinghouse (NKUDIC) is a 

service of the National Institute of Diabetes 

and Digestive and Kidney Diseases (NIDDK). 

The NIDDK is part of the National Institutes 

of Health under the U.S. Department of 

Health and Human Services. Established 

in 1987, the Clearinghouse provides information about diseases of the kidneys and 

urologic system to people with kidney and 

urologic disorders and to their families, 

health care professionals, and the public. 

The NKUDIC answers inquiries, develops 

and distributes publications, and works closely with professional and patient organizations 

and Government agencies to coordinate 

resources about kidney and urologic diseases. 

Publications produced by the Clearinghouse 

are carefully reviewed by both NIDDK 

scientists and outside experts. This fact sheet 

was reviewed by Glenn Chertow, M.D., 

University of California at San Francisco; and 

William J. Stone, M.D., Vanderbilt University. 

This publication is not copyrighted. The 

Clearinghouse encourages users of this fact 

sheet to duplicate and distribute as many 

copies as desired. 

This fact sheet is also available at 

www.kidney.niddk.nih.gov. 

U.S. DEPARTMENT OF HEALTH 

AND HUMAN SERVICES 

National Institutes of Health 

NIH Publication No. 06–4694 

May 2006