Amyloid light-chain (AL) amyloidosis is a rare but serious disease in which abnormal proteins, called amyloid fibrils, build up in the body’s tissues and organs. As this buildup gets worse, AL symptoms may become more severe. Doctors use a staging system to understand how far the disease has progressed. Knowing the stage helps doctors estimate the amount of organ damage, determine your likely prognosis (outlook), and figure out your best treatment options.

In this article, we’ll explain how doctors assess the stages of AL amyloidosis and what the stages mean. Understanding how this disease may affect your body can allow you to have more confident conversations with your healthcare team.

How Amyloid Light-Chain Amyloidosis Progresses

AL amyloidosis that affects more than one organ is called primary systemic amyloidosis. In this form, pieces of antibody proteins build up in different tissues and organs. As these amyloid fibrils (protein clumps) collect, they cause damage that can impair organ function and lead to serious symptoms.

Doctors use various tests to track how the disease is progressing and check for signs of amyloidosis. A sign is something that can be seen or measured by someone else, such as changes in lab results, leg swelling, or an enlarged tongue (a classic sign of AL amyloidosis). These signs often occur with symptoms — sensations that only you can feel, like pain, fatigue (persistent, extreme tiredness), or shortness of breath.

Different cases of AL amyloidosis can progress at different rates. For many people, the disease gets worse quickly. AL amyloidosis most often affects the kidneys and the heart. As amyloid fibrils build up, these vital organs become more damaged and stop working as they should.

Different cases of AL amyloidosis can progress at different rates.

AL amyloidosis can also involve other parts of the body, including the digestive system, liver, and nervous system. Eventually, affected organs can stop working altogether. Recognizing how the disease progresses can help explain why you’re experiencing certain symptoms or your doctor is ordering specific tests.

Read more about how AL amyloidosis can affect the organs.

AL Amyloidosis and the Bone Marrow

Amyloidosis starts in the bone marrow — the soft, spongy tissue inside bones where blood cells are made. There, white blood cells called plasma cells can develop abnormalities and start producing faulty proteins called light chains. These light chains can form harmful amyloid deposits in the body’s tissues and organs.

Doctors can often detect signs of AL amyloidosis with lab tests, even before symptoms appear. These early signs include:

• Monoclonal gammopathy — Abnormal light chains of antibodies are found in the blood.
• Signs of organ involvement — Tests show signs of organ dysfunction (one or more organs aren’t working properly).

If your doctor sees these signs, they may recommend more testing to check for amyloidosis. If left untreated, amyloid protein levels will continue to rise, amyloid deposits will build up, and you’ll start noticing symptoms. The way the disease progresses will depend on which organs are affected.

Read about the connection between AL amyloidosis and blood cell cancers.

AL Amyloidosis and the Kidneys

Your kidneys act as filters, removing waste and extra fluids from your blood while keeping important proteins where they belong. When amyloid deposits build up in the kidneys, they interfere with this filtering process. This can lead to nephrotic syndrome, a condition that occurs when the kidneys leak protein into the urine.

Doctors can detect nephrotic syndrome using blood and urine tests. Signs may include:

• Too much albumin protein (a key protein) in the urine
• Too little albumin in the blood
• High levels of fats and cholesterol in the blood

In some cases, your doctor may recommend a kidney biopsy, which involves removing a small tissue sample to confirm a diagnosis. You may not notice any symptoms at first, but if the condition progresses, you might experience symptoms such as edema — swelling in the legs, feet, or ankles.

If amyloid deposits prevent the kidneys from doing their job, renal failure (kidney failure) can result. At this stage, called end-stage kidney disease, a person may need dialysis. This treatment helps filter the blood when the kidneys can no longer do it on their own.

AL Amyloidosis and the Heart

When amyloid proteins build up in the heart, the walls of this critical organ become thickened and stiff. Amyloid deposits make it harder for the heart to fill with blood and pump it efficiently to the rest of the body. As amyloidosis progresses, heart function declines and can lead to heart failure and other complications. These heart-related issues include:

• Stiff heart walls that can’t relax and fill with blood normally
• Weakened pumping action, reducing blood flow to the body
• Arrhythmias (irregular heartbeats)
• Disrupted electrical signals in the heart
• Dangerous blood clots
• Sudden cardiac death (in rare cases)

Cardiac amyloidosis often progresses quickly. To monitor your heart health, your doctor may use imaging tests, such as an echocardiogram or MRI. These tests can show if the heart muscle is thickened or beating abnormally.

Cardiac amyloidosis often progresses quickly.

AL Amyloidosis and the Digestive System

Amyloid protein buildup in the gastrointestinal (digestive) system can affect your appetite and cause uncomfortable symptoms. Some symptoms, like acid reflux and nausea, may be caused directly by amyloid deposits. Others, such as diarrhea, constipation, and weight loss, may result from other issues, such as nerve damage, as amyloidosis progresses.

AL Amyloidosis and the Nervous System

Amyloid light-chain proteins can collect in the nerves, blocking them from carrying messages between the brain and the rest of the body. This can lead to neuropathy, or nerve damage. Early symptoms often include tingling, burning, or pins-and-needles sensations, usually starting in the feet. These symptoms happen when smaller nerves are affected first.

As amyloidosis progresses, larger nerves may also become involved. This can lead to numbness, muscle weakness, or problems with balance and coordination.

How AL Amyloidosis Is Staged

If you’re diagnosed with AL amyloidosis, your doctor may assess the stage of your disease. Staging helps describe how advanced the condition is, ranging from 1 to 4. Knowing your stage can help you and your care team better understand how much organ damage there is and what your prognosis may be.

Knowing your stage can help you and your care team better understand how much organ damage there is and what your prognosis may be.

There are several staging systems for AL amyloidosis, so different doctors may use different methods to determine your stage. Some staging systems focus more on heart damage, while others look at how the kidneys are affected.

Your amyloidosis stage is determined using biomarkers — molecules in blood or urine that can signal disease. Biomarkers tests help show how well your organs are working and how much damage may have occurred.

Mayo Clinic Staging System

In 2004, Mayo Clinic researchers created a system to measure amyloidosis-related heart damage. The current version, updated in 2012, uses three biomarkers:

• N-terminal pro-brain natriuretic peptide (NT-proBNP) — The heart makes NT-proBNP when it’s under pressure or not working well.
• Cardiac troponin T (cTnT) — This molecule appears in the blood when heart cells are damaged.
• Difference between involved and uninvolved free light chains (dFLC) — This number is a measure of how many light-chain proteins in the blood are abnormal, helping identify amyloid buildup.

To determine your stage, doctors compare your biomarker levels to standard cutoffs:

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

Here’s how the Mayo Clinic staging system breaks down:

• Stage 1 — All biomarkers are within the normal range.
• Stage 2 — One biomarker is elevated.
• Stage 3 — Two biomarkers are elevated.
• Stage 4 — All three biomarkers are elevated.

The Mayo Clinic staging system helps doctors monitor how the disease is progressing and adjust treatment as needed. In general, people with higher stages tend to have more serious heart problems and a shorter life expectancy. In a 2012 study, people diagnosed with stage 1 AL amyloidosis lived a median of 7.8 years, whereas those with stage 4 AL amyloidosis lived a median of 5.8 months after diagnosis. Median survival is the point at which half the people in the group lived longer and half lived less.

Other Cardiac Staging Systems

Since the original Mayo Clinic system was introduced, other staging methods have been developed to better understand how amyloidosis affects the heart. One version, sometimes called the Mayo 2004 or European modification, breaks stage 3 amyloidosis into two subgroups — 3A and 3B.

In both subgroups, NT-proBNP and cTnT levels are above normal levels. However, in stage 3B, NT-proBNP levels are extremely high — at least 8,500 nanograms per liter — which is linked to a shorter life expectancy. People with stage 3A live an average of 15 months after diagnosis, whereas people with stage 3B live an average of four months.

Although NT-proBNP is a useful biomarker, it can be hard to measure. Some doctors instead use a different test based on brain natriuretic peptide (BNP) — a similar protein that’s easier to test for. This system also swaps cTnT for cardiac troponin I (cTnI), another marker of heart damage.

Here’s how this BNP-based staging system works:

• Stage 1 — BNP is less than 81 picograms per milliliter, and cTnI is less than 0.1 nanograms per milliliter.
• Stage 2 — Either BNP is greater than 81 picograms per milliliter or cTnI is greater than 0.1 nanograms per milliliter.
• Stage 3 — BNP is greater than 81 picograms per milliliter, and cTnI is greater than 0.1 nanograms per milliliter.
• Stage 3B — BNP is greater than 700 picograms per milliliter, and cTnI is greater than 0.1 nanograms per milliliter.

People with stage 3B amyloidosis tend to have a worse disease outlook and a shorter lifespan than people with lower-stage disease.

Kidney Staging Systems

Doctors use kidney staging to understand how much damage amyloidosis has caused in your kidneys. Two key factors determine your stage. One is proteinuria, which means there’s too much protein in your urine. Higher levels typically indicate kidney damage. The other factor is estimated glomerular filtration rate (eGFR), a number that shows how well your kidneys are filtering waste from your blood. A lower eGFR indicates reduced kidney function.

Kidney staging in AL amyloidosis often follows this system:

• Stage 1 — An eGFR above 50 and proteinuria under 5 grams a day
• Stage 2 — Either an eGFR below 50 or proteinuria over 5 grams a day
• Stage 3 — An eGFR below 50 and proteinuria over 5 grams a day

Your kidney stage helps predict your risk of needing dialysis due to kidney failure. According to one study, people with renal stage 1 amyloidosis have a 1 percent chance of needing dialysis within two years of diagnosis, whereas people with stage 3 disease have a 48 percent chance.

If your kidney stage is higher, your doctor may recommend more frequent follow-ups to monitor your kidney health closely. Early detection of changes allows your care team to adjust your treatment and help protect your kidney function over time.

Talk With Others Who Understand

MyAmyloidosisTeam is the social network for people with amyloidosis and their loved ones. On MyAmyloidosisTeam, members come together to ask questions, give advice, and share their stories with others who understand life with amyloidosis.

Are you living with AL amyloidosis? What stage of AL amyloidosis were you diagnosed with? Share your experience in the comments below, or start a conversation by posting on your Activities page.