If you are diagnosed with amyloidosis, your doctor will try to determine the stage (how advanced the disease is). As you undergo amyloidosis treatments, your doctor may recommend tests to determine whether the disease is progressing (getting worse). These tests can help your doctor estimate your outlook (also called prognosis).
There are several types of amyloidosis. Each type is caused by different proteins and affects different organs. The type of amyloidosis a person has determines how their condition will be staged.
Amyloid light-chain amyloidosis (AL) or primary amyloidosis is a disorder caused by abnormal plasma cells (a type of white blood cell). Normal plasma cells produce infection-fighting antibodies, which are made up of heavy-chain and light-chain proteins. In amyloidosis, abnormal plasma cells make abnormal amyloid light chains. These proteins form clumps called amyloid fibrils that build up in the heart and other organs, causing damage. AL amyloidosis produces nonfunctional light chains.
Doctors use several different systems to stage AL amyloidosis. Although stages are calculated in different ways, they all describe your outlook and help you understand how well your organs are working. Some systems focus on heart damage, and others stage renal (kidney) disease.
One common staging system for AL amyloidosis is the Mayo Clinic system. This system estimates the amount of heart damage.
The most recent version of this system determines the stage based on three biomarkers (molecules that serve as signs of disease). Two of the biomarkers, N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT), are signals of heart damage. The other biomarker (dFLC) is called the “difference between involved and uninvolved free light chains.” This biomarker describes how many of the body’s light-chain proteins are amyloid proteins compared with normal light-chain proteins.
Normal levels of these biomarkers are:
The higher each of these biomarkers is, the later the amyloidosis stage and the more severe the disease is. People with early-stage AL amyloidosis live longer than people with advanced disease:
Some doctors use a system that was based on the original Mayo Clinic staging system but contains a slight modification. The European modification considers NT-proBNP and cTnT levels but not dFLC levels. The stages are grouped as follows:
Some hospitals are not able to test for NT-proBNP. Therefore, researchers came up with a different system using a similar biomarker called BNP. This system also considers the cTnI biomarker in place of cTnT.
Normal levels of these biomarkers are less than 81 picograms per milliliter BNP and less than 0.1 nanograms per milliliter for cTnI.
People with AL amyloidosis who have normal levels of both biomarkers have stage 1 disease. If either biomarker is elevated, the amyloidosis is at stage 2. Having higher-than-normal levels of both biomarkers indicates stage 3 disease. If BNP levels are especially high — more than 700 picograms per milliliter — then doctors say amyloidosis is at stage 3b.
Other prognostic factors besides stage also influence the outlook for AL amyloidosis. These include high levels of plasma cells, the presence of monoclonal protein (also called M protein) in the urine, and certain gene changes.
Other staging systems help doctors understand the extent of kidney damage. Estimated glomerular filtration rate (eGFR) and proteinuria (protein in the urine) are biomarkers that describe how well the kidneys are working.
Usually, eGFR is more than 50 milliliters per minute per 1.73 square meters, and proteinuria is less than 5 grams per 24 hours. Having abnormal levels means that the AL amyloidosis is at a later stage:
Doctors use heart staging to determine survival rates for AL amyloidosis. However, kidney staging is used to predict whether someone will develop kidney failure. People with later-stage AL amyloidosis are more likely to have kidney problems and need to undergo dialysis treatments in the future.
There are two types of amyloidosis caused by the transthyretin (TTR) protein. Hereditary ATTR amyloidosis is caused by gene mutations. In this condition, the liver produces abnormal TTR. Wild-type ATTR amyloidosis develops when the liver makes high levels of normal TTR protein.
Researchers recently developed a system that can help determine the disease stage for people with either hereditary or wild-type ATTR amyloidosis who have heart symptoms. This system considers biomarkers related to both heart damage and kidney damage and can be used to predict outlook.
This ATTR staging system uses the cardiac biomarker NT-proBNP and the kidney biomarker eGFR. It defines normal biomarker levels as less than 3,000 nanograms per liter for NT-proBNP and more than 45 milliliters per minute for eGFR.
People with stage 1 ATTR amyloidosis have normal levels of both biomarkers. Stage 2 amyloidosis is defined as abnormal levels of either biomarker. Those with stage 3 disease have abnormal levels of both biomarkers. These stages help predict survival:
Researchers also recently developed a second staging system for wild-type ATTR amyloidosis. This system is similar to the previous one but uses the biomarkers NT-proBNP and cTnT. People with abnormal levels of these biomarkers have a poor outlook compared to people with normal levels.
Hereditary amyloidosis can affect multiple organs and tissues. When amyloid deposits build up in the nerves, doctors may call it familial amyloid polyneuropathy. However, this term is now rarely used.
Several different systems are used to classify the severity of hereditary ATTR amyloidosis within the nervous system. These systems use amyloidosis symptoms to stage disease.
One common system, the Coutinho staging system, was developed several decades ago. People with more severe symptoms have advanced disease:
Another system is the polyneuropathy disability scoring system. It scores symptoms in a slightly different way:
Researchers may also use several other staging systems. These systems often share some similarities but classify symptoms in different ways. Other systems include the Portuguese classification system, neuropathy symptom score, autonomic dysfunction scoring, neurologic disability score, and neuropathy impairment score.
AA amyloidosis develops when the body experiences ongoing inflammation. Chronic infections, autoimmune disorders, and other immune diseases can all make the body produce amyloid protein, leading to AA amyloidosis.
Researchers have not developed a staging system for AA amyloidosis, so survival rates can’t be grouped by stage. Overall, people with AA amyloidosis live for an average of 11 years after being diagnosed. However, doctors can use several factors to identify whether the amyloidosis is progressing and estimate the outlook.
Some people with AA amyloidosis experience kidney failure, which often leads to poor outcomes. Signs that the kidney is not working correctly indicate that a person has a worse outlook. These signs include proteinuria, low levels of albumin protein, a need for dialysis, and high levels of creatinine (a waste product that is normally removed by the kidneys). Other factors that increase the risk of a poor outcome include older age, high levels of amyloid protein in the blood, and heart or liver damage.
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