Risk Factors of Amyloidosis

Executive Summary:

Amyloidosis is a rare disease condition that happens when amyloid, an abnormal protein, accumulates and builds up in the organs, interfering with their everyday activities and functions. Amyloid is called an abnormal protein since it isn’t generally found in the body. Amyloidosis can affect body parts like the kidneys, liver, heart, spleen, digestive tract, nervous system etc. Risk factors of Amyloidosis refer to the factors that can increase the chance or probability of developing a disease or illness. Some of the significant risk factors of Amyloidosis includes age, infection or other conditions, kidney disease, inflammatory diseases, heredity, and gender. Several complications due to abnormal amyloid protein formed in the organs where the amyloid build-up occurs, such as in kidneys, heart, nervous system, are other risk factors associated with amyloidosis.

What are the Risk Factors

Amyloidosis Risk Factors refer to the factors that can increase a person’s chance or probability of developing a disease or illness. Risk factors are not the direct cause of an illness but can influence its development. We can see that some people with no risk of Amyloidosis develop the disease, whereas some others with several risk factors don’t grow.

The cause of amyloidosis disease condition is unknown. What causes the production of this abnormal protein, amyloid, and its build-up in the tissues is still undiscovered ​1​.


  • Age: Older people (say, 50 years and more) are at a higher risk of Amyloidosis. While majority of people diagnosed with AL or Amyloid light Chain Amyloidosis, which is the primary form of the disease, are aged 40 and above, the risk of amyloidosis increases as one ages.
  • Infections or other diseases: A chronic illness, inflammation or any form of the disease can increase a person’s risk of an amyloidosis disease condition, in addition, most cases of Amyloidosis will be linked with other diseases or illnesses. For example, studies reveal that about 12% to 15% of people diagnosed with multiple myeloma also develop Amyloidosis.
  • People who have any form of kidney disease (like a last-stage renal disease) or has been on dialysis for some years are at risk of Amyloidosis. 
  • People having inflammatory diseases like rheumatoid arthritis are at a higher risk of developing secondary Amyloidosis. Rheumatoid arthritis also vastly increases the risk of systemic Amyloidosis. An early diagnosis and treatment of amyloidosis can help manage and relieve Rheumatoid arthritis ​2​.
  • Family History/Heredity: Amyloidosis can run in families. Having a family history of this disease can increase a person’s risk. It could result from any genetic mutation passed down from one generation to another.
  • Gender: Researches show that men are more prone to Amyloidosis than women.
  • Genetic mutations: Certain genetic mutations can predispose individuals to hereditary forms of amyloidosis. These mutations affect proteins involved in the formation of amyloid deposits, such as transthyretin (TTR), apolipoprotein A1 (APOA1), and gelsolin (GSN). Different mutations are associated with specific types of amyloidosis.
  • Chronic inflammatory diseases: Chronic inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, and ulcerative colitis, can increase the risk of developing secondary amyloidosis. Persistent inflammation triggers the production of amyloid proteins, leading to amyloid deposits in various organs.
  • Kidney disease: Chronic kidney disease, particularly in individuals requiring long-term dialysis, is a risk factor for developing dialysis-related amyloidosis. The accumulation of beta-2 microglobulin, a protein normally cleared by healthy kidneys, can lead to amyloid deposits in the joints and other tissues.
  • Plasma cell disorders: Conditions involving abnormal plasma cells, such as multiple myeloma (a type of blood cancer) and monoclonal gammopathy of undetermined significance (MGUS), increase the risk of systemic light-chain (AL) amyloidosis. In AL amyloidosis, abnormal plasma cells produce excessive light chains, which can form amyloid deposits in organs.

Complications due to Amyloidosis

Amyloidosis can have a severe impact on several body parts. The complications and damage depend on the organs where the amyloid build-up happens. It can affect:

  • The Kidneys: the abnormal amyloid protein can affect the kidney’s filtering system, causing protein leakage from your blood into the urine. It lowers the efficiency of kidneys in removing waste from the body, which will eventually lead to kidney failure and the need for dialysis for the rest of your life.
  • Heart: Amyloid accumulation affects the heart’s ability to pump blood. When the amount of blood pumped with each heartbeat decreases, a person may experience shortness of breath. Amyloidosis can disrupt the heart rhythm by interfering in the heart’s electrical system. The condition can be life-threatening ​3​.
  • Nervous system: amyloid affecting the nervous system can cause drastic impacts on a person’s body and health condition. Due to amyloid build-up in the nervous system, one may experience numbness, pain or a tingling sensation in their fingers, or a burning sensation in the soles or toes of their feet. Amyloidosis associated with the nerves that control and coordinate your bowel function, causes bouts of alternating diarrhoea and constipation. If it is related to the nerve that regulates blood pressure, it can cause some balance issues, like you may feel like you are going to faint after standing up in a hurry or suddenly. 
  • Organ Dysfunction: Amyloid deposits can impair the normal functioning of organs such as the heart, kidneys, liver, gastrointestinal tract, nervous system, and others. This can result in symptoms specific to the affected organ, such as heart failure, kidney damage, liver dysfunction, digestive problems, neuropathy, and others.
  • Gastrointestinal Complications: Amyloid deposits in the digestive system can cause symptoms like malabsorption, diarrhea, constipation, and gastrointestinal bleeding.
  • Bleeding and Clotting Issues: In certain types of amyloidosis, such as AL amyloidosis, abnormalities in clotting factors can lead to an increased risk of bleeding or blood clot formation.
  • Amyloidosis of the Skin and Soft Tissues: Amyloid deposits in the skin and soft tissues can lead to skin nodules, purpura (small bleeding under the skin), and other dermatological manifestations.

It’s important to note that the specific complications can vary depending on the type of amyloidosis and the organs affected. Early diagnosis, appropriate treatment, and management of underlying conditions are crucial in minimizing complications and improving outcomes for individuals with amyloidosis.


  1. 1.
    Saunders CN, Chattopadhyay S, Huhn S, et al. Search for AL amyloidosis risk factors using Mendelian randomization. Blood Advances. Published online July 6, 2021:2725-2731. doi:10.1182/bloodadvances.2021004423
  2. 2.
    Nakamura T. Clinical strategies for amyloid A amyloidosis secondary to rheumatoid arthritis. Modern Rheumatology. Published online April 2008:109-118. doi:10.3109/s10165-008-0035-2
  3. 3.
    Hörnsten R, Pennlert J, Wiklund U, Lindqvist P, Jensen SM, Suhr OB. Heart complications in familial transthyretin amyloidosis: impact of age and gender. Amyloid. Published online May 12, 2010:63-68. doi:10.3109/13506129.2010.483114