Stages of Amyloidosis

Executive Summary:

The staging of Amyloidosis cancer describes a disease condition in terms of its gravity and location. While Amyloidosis staging depends on the kind of disease condition that a person has, out of all the amyloidosis types, AL amyloidosis or Amyloid light-chain amyloidosis is the most common type. The disease results from abnormal plasma cells creating abnormal amyloid light chains, while originally a plasma cell produces antibodies that help our body to fight infections. A recent system analyses the stage of AL amyloidosis by using biomarkers. The stages of Amyloidosis ranges from stage I to stage IV depending upon the type of Amyloidosis. There are three stages of AL amyloidosis.

Another staging system that is ATTR staging system uses a cardiac biomarker NT-proBNP and the kidney biomarker eGFR to carry out the staging of Amyloidosis. Stage 0- stage 3 are the stages of hereditary, although, ATTR amyloidosis associated with the nervous system.

Staging system of Amyloidosis

 If a person is diagnosed with Amyloidosis, the doctor will use various diagnostic tests to determine the disease stage. In addition to general treatment, knowing the stage will help the healthcare team to understand how advanced the disease condition is and what treatment plan can be employed to treat the condition. Staging a disease condition like Amyloidosis will help predict the patient’s prognosis. Staging is vital in to determine a patient’s survival rate.

Amyloidosis can be of different types. Different types of protein build-up cause each type, therefore the Amyloidosis staging depends on the kind of disease condition that a person has. Out of all the amyloidosis types, AL amyloidosis or Amyloid light-chain amyloidosis is the most common type.

The disease results from abnormal plasma cells creating abnormal amyloid light chains, while originally, a plasma cell produces antibodies that help our body to fight infections. Still, in the case of AL amyloidosis, plasma cells have abnormal proteins, which form clumps called amyloid fibrils that eventually build up in different organs like the heart and cause severe damage.

Stages of Al-Amyloidosis

Doctors use different systems to stage Amyloid Light Chain or AL-amyloidosis, additionally, most of these systems focus on to what extent the protein build-up has damaged the heart and kidney.

A recent system analyses the stage of AL amyloidosis by using biomarkers. Biomarkers are molecules that serve as markers or signs of a disease condition, moreover these biomarkers indicate the extent of heart damage caused by the light chains. The biomarkers cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) signals any possible heart damage.

biomarker (dFLC), called the “difference between involved and uninvolved free light chains”, portrays how many among the light-chain proteins of the body are amyloid proteins compared to the typical light-chain protein fibrils ^​1,2​.

Levels of biomarkers

The standard or normal levels of the biomarkers mentioned above are as follows:

• cardiac troponin T or cTnT: 0.025 nanograms per millilitre or less
• N-terminal pro-brain natriuretic peptide or NT-proBNP: 1,800 nanograms per litre or less
• dFLC:180 milligrams per litre or less

The range of these biomarkers indicates the stage of the disease. Amyloidosis is advanced in higher range.

• Patients with stage 1 AL amyloidosis have all the biomarkers at normal levels. They live for 7-8 years post disease diagnosis, approximately.
• Patients with stage 2 AL amyloidosis have one biomarker above normal levels (either cTnT or NT-proBNP) and the other two at normal levels. The average survival rate is around 3.5 years post-diagnosis.
• Patients with stage 3 AL amyloidosis are slightly severe, as two biomarkers are above normal levels, moreover, the average duration of survival is around 14 months post diagnosis.
• Patients with stage 4 AL amyloidosis have all three biomarkers above normal levels, indicating a very advanced stage of the disease. Additionally, the average a patient may live post-diagnosis is for around 5.8 months. 

The lowest the stage of the disease, the highest will be the survival rate. 

Cardiac Stages Of AL Amyloidosis Using BNP Biomarker

Some researchers made use of a BNP biomarker instead of an NT-proBNP. The system uses a cTnI biomarker instead of the cTnT biomarker.

Normal levels of these biomarkers are:

BNP- less than 81 picograms per milliliter is normal.

cTnI- less than 0.1 nanograms per milli-litre.

Stages

1.both these biomarkers will be at normal levels.

2.if either of these biomarkers is above the normal range.

3.if both the biomarkers are above the normal levels. Indicates a severe stage of Amyloidosis.

3b.if the BNP biomarker level is beyond 700 picograms per milliliter.

Other factors besides stage that influence AL Amyloidosis conditions are M protein or monoclonal protein, specific gene mutations, high levels of plasma cells in the urine etc.

AL Amyloidosis: Kidney Staging 

While specific staging systems can help doctors determine the extent of kidney damage caused by AL amyloidosis disease condition, the biomarkers preferred for kidney staging are proteinuria (protein in the urine) and estimated glomerular filtration rate or eGFR. The usual range of proteinuria is considered less than 5 grams per 24 hours, and that of eGFR is regarded as 50 millilitres per minute per 1.73 square meters ^​3​.

Hence the kidney staging of AL Amyloidosis based on the levels of these biomarkers are as follows:

Stages

1- Both (proteinuria and eGFR) biomarkers are at normal levels.

2- generally, proteinuria exceeds the average level, or eGFR is below the normal range.

3- both eGFR and proteinuria are at abnormal levels. 

Doctors and specialists generally use heart staging of AL Amyloidosis to evaluate a person’s survival rate. However, kidney staging of AL Amyloidosis can be vital in determining whether the amyloid build-up will cause kidney failure or not. Patients diagnosed with advanced stage of AL amyloidosis are more likely to develop kidney problems, additionally such people will need to undergo dialysis treatments in the future. 

Stages of ATTR Amyloidosis

The protein transthyretin causes ATTR amyloidosis, called the TTR protein. There are two types of Amyloidosis caused by TTR protein: hereditary ATTR amyloidosis and Wild-type ATTR amyloidosis. Hereditary ATTR amyloidosis is a result of gene variations. In this disease condition, the liver produces abnormal TTR proteins. Wild-type ATTR amyloidosis is due to the liver producing high levels of normal TTR proteins.

Cardiac Staging for ATTR Amyloidosis

Recently doctors and researchers have developed a system to determine the staging of hereditary and wild-type ATTR amyloidosis that has affected the heart. The system uses biomarkers to evaluate the damage caused to the heart and kidney by the protein build-up.

The ATTR staging system uses a cardiac biomarker NT-proBNP and the kidney biomarker eGFR to carry out the staging of Amyloidosis. The average levels of these biomarkers are:

NT-proBNP: less than 3,000 nanograms per litre

eGFR: more than 45 milliliters per minute

• Patients with stage 1 ATTR amyloidosis have both these biomarkers at normal levels and moreover they are expected to live an average of 5 years post disease diagnosis.
• In Stage 2 ATTR Amyloidosis, any one of the two biomarkers will be above the normal levels, additionally, the life expectancy is estimated at around 3.9 years post-diagnosis.
• Patients with stage 3 ATTR amyloidosis have these biomarkers above the stipulated levels. People are expected to live for about two years post-diagnosis.

Also, another staging system is used to stage wild-type ATTR amyloidosis. The biomarkers used for the study are cTnT and NT-proBNP.

Stages of Hereditary Amyloidosis concerning the Nervous System

Hereditary amyloidosis conditions can occur in multiple tissues and organs of the body. Familial Amyloid polyneuropathy is a condition where amyloid protein builds up in the nerves.

Several staging systems are used to stage hereditary ATTR amyloidosis associated with the nervous system. One such system is the Coutinho staging system. Staging as per this system is as follows:

• Stage 0 – patients have no signs or symptoms.
• Stage 1 – patients have mild symptoms and signs. They can walk or move but will experience some difficulties.
• Stage 2 – patients will experience moderate signs and symptoms and may need aid while walking.
• Stage 3 —patients will experience severe symptoms and signs—increased difficulty to walk and may need a wheelchair to move. 

Another system used to stage ATTR Amyloidosis is the polyneuropathy disability scoring system. The system evaluates the symptoms and determines the stage slightly differently.

Stages

0 – patients will experience no signs or symptoms.

1 – patients may experience unusual sensations like numbness or tingling sensations in the legs. They may find it difficult to walk. 

2– patients may experience increased difficulty in walking.

3a – patients may require a single mobility aid such as a crutch or cane to walk.

3b – patients may require increased support, like two canes or walking crutches.

4 – patients may not walk and require a wheelchair.

There are other staging systems used to determine the stage of ATTR amyloidosis. They include neuropathy symptom score, the Portuguese classification system, autonomic dysfunction scoring, neuropathy impairment score and neurologic disability score.

Stage Determination OF AA Amyloidosis

AA amyloidosis results from prolonged or chronic inflammation or infections in the body. Autoimmune disorders or any chronic illnesses can cause the body to produce abnormal proteins leading to an AA amyloidosis condition.

There are no definite systems or methods to evaluate the stages of AA amyloidosis. Hence, the survival rate of people diagnosed with AA amyloidosis cannot be grouped as per the stages. But estimates reveal that people diagnosed with AA amyloidosis are expected to live for 11 years. 

By looking at the spot where the abnormal protein build-up has happened, doctors can determine the severity of the disease condition. Some people with AA amyloidosis will undergo kidney dysfunction. A person with a failed kidney will experience signs like low albumin protein levels, proteinuria, high levels of creatinine, and these people will probably require dialysis. Other risk factors of AA amyloidosis include old age, liver or heart damage, high levels of amyloid protein in the blood etc. 

References