If you’ve been diagnosed with amyloidosis, your doctor will assess how far the disease has progressed. This is called staging. As you go through amyloidosis treatment, your doctor may order tests to determine whether the disease is staying the same, getting better, or getting worse. These results can help your doctor estimate your prognosis (outlook) and guide your treatment plan.

There are several different types of amyloidosis, and each affects the body a little differently. The type you have depends on which abnormal protein is involved and which organs are affected. Because of that, doctors use different staging systems for different types. Tailoring staging to your specific type helps provide a more accurate picture of how advanced the disease is and allows for personalized care.

Staging Amyloid Light-Chain Amyloidosis

Amyloid light-chain amyloidosis (AL), or primary amyloidosis, is the most common type of amyloidosis. Doctors use several systems to stage this condition, depending on which organs are affected. Some systems focus on heart damage, and others focus on how well the kidneys are working.

As you go through amyloidosis treatment, your doctor may order tests to determine whether the disease is staying the same, getting better, or advancing.

Mayo Clinic Staging System

One common staging system for AL amyloidosis was developed at Mayo Clinic. This system looks at heart damage using biomarkers, which are substances in your blood that show how your heart is working. The current version uses three biomarkers:

• N-terminal pro-B-type natriuretic peptide (NT-proBNP) — This substance rises when the heart is under stress or not pumping well.
• Cardiac troponin T (cTnT) — This protein shows up when heart muscle cells are damaged.
• Difference between involved and uninvolved free light chains (dFLC) — This measurement shows how many of your body’s light-chain proteins are abnormal amyloid proteins.

Researchers set cutoff levels that indicate whether a biomarker is in the normal or high range:

• NT-proBNP — 1,800 nanograms per liter or less
• cTnT — 0.025 nanograms per milliliter or less
• dFLC — 180 milligrams per liter or less

Based on how many of your biomarkers are elevated, doctors can determine your stage of AL amyloidosis and estimate your prognosis using median overall survival — the time at which half of people are still alive after diagnosis.

These numbers reflect averages from large groups of people and aren’t meant to predict how long any one person will live. Instead, they give doctors a way to talk with you about treatment options, how aggressive to be with therapy, and how to plan your care together.

The European Modification

Some doctors use a modified version of the original Mayo Clinic staging system to help identify people who are at very high risk of amyloidosis. This version, sometimes called the European modification, relies on just two heart-related biomarkers — NT-proBNP and cTnT. This simplified approach can help doctors quickly identify people who may need more urgent or intensive treatment.

The European system has four stages.

Cardiac Staging Using Brain Natriuretic Peptide

Some hospitals may not be equipped to test for NT-proBNP, so doctors may use a different system using a similar heart biomarker called brain natriuretic peptide (BNP). This system also uses cardiac troponin I (cTnI) instead of cTnT to check for heart damage.

For BNP, a normal level is less than 81 picograms per milliliter. For cTnI, a normal level is less than 0.1 nanograms per milliliter. Doctors stage amyloidosis based on these test results.

Although their names are different from those in the Mayo Clinic and European staging systems, these biomarkers have the same purpose: to give doctors valuable information about your heart health and help plan treatment decisions.

Kidney Staging for AL Amyloidosis

Doctors use other staging systems to assess the amount of kidney damage. Two important biomarkers help measure kidney function:

• Estimated glomerular filtration rate (eGFR) — Shows how well your kidneys are filtering waste from your blood
• Proteinuria — Refers to protein leaking into the urine, which signals kidney damage

Researchers set cutoffs for eGFR (50 milliliters per minute per 1.73 square meters) and proteinuria (5 grams in 24 hours) to help stage kidney damage in AL amyloidosis. There are three stages.

While heart staging is often used to estimate survival, kidney staging plays a key role in managing AL amyloidosis over time. This process helps identify people at higher risk of kidney failure early, so doctors can take steps that may delay or prevent dialysis (a treatment that filters waste when the kidneys can no longer do it on their own).

Staging ATTR Amyloidosis

The transthyretin (TTR) protein causes two main forms of amyloidosis. Hereditary ATTR amyloidosis results from gene mutations (changes) passed down in families. In this form, the liver produces abnormal TTR. The other form, called wild-type ATTR amyloidosis, develops for unknown reasons. ATTR amyloidosis can affect several organs, including the heart, nervous system, and kidneys.

Staging for Cardiac ATTR Amyloidosis

To help understand how ATTR amyloidosis is progressing, doctors use a staging system based on cutoffs for NT-proBNP (less than 3,000 nanograms per liter) and eGFR (more than 45 milliliters per minute).

By looking at both the heart and kidneys, this staging system provides a fuller picture of how ATTR amyloidosis is affecting the body. The stages help predict median survival.

Researchers also developed a second staging system for wild-type ATTR amyloidosis using NT-proBNP and cTnT. People with abnormal levels of both biomarkers tend to have a poorer outlook than those with normal levels.

Staging Hereditary Amyloidosis in the Nervous System

Hereditary amyloidosis can affect many parts of the body, including the nervous system, which controls movement, sensation, and other important functions. To understand how far the disease has progressed, doctors use staging systems based on the symptoms a person experiences. These systems help track changes over time and plan treatment decisions.

Hereditary amyloidosis can affect many parts of the body, including the nervous system, which controls movement, sensation, and other important functions.

One commonly used system, the Coutinho staging system, focuses on how nerve symptoms affect a person’s ability to walk.

Another system, called the polyneuropathy disability scoring system, offers a more detailed breakdown.

Researchers may also use other staging systems that focus on different types of nerve-related symptoms. These systems rate symptom severity in different ways, but they often have the same goals: to track how the disease changes over time and help plan care.

Examples include:

• Portuguese classification system
• Neuropathy symptom score
• Autonomic dysfunction scoring
• Neurologic disability score
• Neuropathy impairment score

Determining Progression in AA Amyloidosis

AA amyloidosis, also called secondary amyloidosis, develops when the body experiences ongoing inflammation. Chronic infections, autoimmune disorders, and other inflammatory diseases can all make the body produce amyloid protein, leading to AA amyloidosis.

Researchers have developed a new staging system for AA amyloidosis. Poor survival in AA amyloidosis is associated with factors including:

• Age 65 or older
• An eGFR less than 45 milliliters per minute
• NT-proBNP greater than 1,000 nanograms per liter
• BNP greater than 130 nanograms per liter

The number of poor prognostic factors a person has can help predict their outlook. Based on this, one study reported overall survival (the percentage of people still alive 36 months after diagnosis):

• Zero to one factor — 92 percent
• Two factors — 72 percent
• Three factors — 32 percent

Almost everyone with AA amyloidosis has kidney involvement, so researchers have also identified risk factors based on kidney biomarkers:

• People with proteinuria higher than 3 grams per 24 hours and eGFR less than 35 milliliters per minute have a higher risk of serious kidney disease.
• People with one abnormal kidney biomarker have a 24 percent risk of progressing to end-stage kidney failure.
• People with two abnormal kidney biomarkers have a 51 percent risk of kidney failure.

Tracking these risk factors and stages helps doctors identify people at higher risk earlier, so they can intervene and protect kidney function for as long as possible.

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