What is amyloidosis? What happens if it affects the kidneys?

Author: Liu Gang, Chief Physician, Peking University First Hospital

Reviewer: Mao Yonghui, Chief Physician, Beijing Hospital

Amyloidosis is a disease in which a certain type of protein is abnormally folded and cannot be cleared normally, depositing into amyloid fibrils in human tissues and organs, ultimately leading to loss of tissue and organ function.

1. What causes amyloidosis?

There are now more than 30 types of proteins that cause amyloidosis. The most common type is the light chain type, called AL type, which accounts for about 90% in our country. The light chain type is not a classic Mendelian inheritance, but there is a genetic susceptibility. On the basis of the susceptible gene, exposure to certain toxic substances or radiation is prone to abnormal monoclonal mutations.

There is also AA type, which is related to Mediterranean fever or long-term chronic inflammation. Mediterranean fever is a genetic disease that causes the body to have a long-term chronic inflammatory response, producing inflammatory proteins called AA proteins, and the amyloidosis formed by deposition is called AA type amyloidosis. AA type amyloidosis caused by systemic lupus erythematosus and tuberculosis is also the result of long-term chronic inflammation.

There are many other types of amyloidosis, most of which are caused by gene mutations, have a certain familial nature, and may also be acquired mutations.

Amyloidosis basically affects all organs in the body. Because the abnormal protein circulates in the blood, the first place where it is deposited is the blood vessel wall. The first organ affected is different for each person. Some people seek medical treatment as the heart or kidney as the first organ affected, while others seek medical treatment with hepatosplenomegaly, gastrointestinal symptoms, including anorexia and diarrhea as the first symptom.

Today we will learn about renal amyloidosis.

Figure 1 Original copyright image, no permission to reprint

2. What are the symptoms of renal amyloidosis?

Renal amyloidosis mainly occurs in middle-aged and elderly people, with the light chain type being the most common. Clinically, about 90% of cases present as nephrotic syndrome, with proteinuria and edema as the main manifestations, hematuria is not prominent, and there are some systemic manifestations, such as fatigue, weight loss, etc.

Normally, patients with nephrotic syndrome will gain significant weight within a few weeks due to edema, but patients with amyloidosis will also have severe edema without corresponding weight gain. If a patient shows symptoms of nephrotic syndrome but loses weight instead of gaining weight, this is actually a dangerous sign.

There are also cases where the blood pressure is not high. One may have had high blood pressure before, but later found that his blood pressure was normal without taking antihypertensive drugs, or even decreased. The blood pressure was normal before, but later became very low. This is also a dangerous signal.

Some cases involve the location of the interstitial tubules, do not produce large amounts of proteinuria, and manifest as chronic renal failure. This may be more hidden and less easy to detect.

Abnormal protein deposits can be deposited in various parts of the kidney, including the glomerulus, renal capillaries, and renal interstitium. Accumulation to a certain amount will lead to renal failure. Generally speaking, renal failure in clinical practice is generally not light chain type, but other types, because light chain type also seriously affects other organs in the body, especially the heart. In fact, it is difficult for patients to survive to the dialysis stage. They may die due to heart involvement before renal failure occurs.

3. How to diagnose renal amyloidosis?

If renal amyloidosis is suspected, relevant tests should be done. First, blood and urine immunofixation electrophoresis should be done to see if there are monoclonal light chains. If nothing is found but there is a high suspicion, blood and urine free light chain detection and analysis should also be done. If conditions permit, a tissue biopsy should be performed, and pathology is the gold standard for diagnosis.

Figure 2 Original copyright image, no permission to reprint

The second is typing. The main method currently adopted is to use immunofluorescence or immunohistochemistry to perform corresponding specific staining of pathogenic proteins to help with qualitative analysis.

There is now a more mature and advanced method called mass spectrometry analysis, which uses mass spectrometry to find the cause of the disease. For most unclassified amyloidosis, mass spectrometry analysis can identify the pathogenic protein.

After the diagnosis and classification are clear, the next step is treatment. For AA type renal amyloidosis, it is important to find the upstream disease. If it is caused by a chronic autoimmune disease, the main treatment is to control the autoimmune disease. Amyloidosis caused by genetic abnormalities is relatively rare, and there is basically no specific treatment method in clinical practice. For light-chain amyloidosis, the current therapeutic effect of autologous hematopoietic stem cell transplantation should be said to be the best. Chemotherapy regimens based on bortezomib can also be considered for treatment. The chemotherapy regimen developed in recent years with CD38 monoclonal antibodies combined with bortezomib as the main drug can further improve the survival rate. If these treatment regimens cannot be carried out, the MPT chemotherapy regimen has also been proven to have a certain therapeutic effect.

At present, cure of renal amyloidosis is a relatively high expectation, but in fact it can be achieved for some patients. Autologous stem cell transplantation or CD38 monoclonal antibody makes it possible to cure some patients with light-chain amyloidosis.