What Is Amyloidosis?
Amyloidosis is a rare disorder characterized by the deposition of hyaline proteinaceous material called amyloid in the body's organs. Amyloid is nothing but an abnormal form of protein produced by the plasma cells of the body. The most commonly involved organs are the kidney, heart, liver, etc.
What Are the Types of Amyloidosis?
The types of amyloidosis include:
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AL (Amyloid Light Chain) Amyloidosis - It is known as the immunoglobulin light chain amyloidosis or primary amyloidosis and is the most common type. The commonly involved organs in this type of amyloidosis include the kidneys, heart, liver, and nerves.
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AA (Serum Amyloid A) Amyloidosis - It is also known as secondary amyloidosis. It is characterized by the deposition of a protein called serum amyloid A. This protein is usually produced in response to inflammation or infections. The commonly involved organs in this type of amyloidosis include the kidneys, spleen, and liver.
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Hemodialysis Associated Amyloidosis - It is considered one of the serious complications of dialysis and is characterized by the deposition of amyloid fibrils containing B2 microglobulin in the bone, viscera, and periarticular structures.
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Hereditary Amyloidosis - It is also known as familial amyloidosis as it occurs as an inherited disorder. It is mostly associated with a defect in a protein called transthyretin (TTR) produced by the liver.
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Wild-type Amyloidosis - It is also known as senile systemic amyloidosis. It mainly affects the heart and is characterized by the deposition of a normally produced transthyretin protein in the organs for an unknown reason.
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Localized Amyloidosis - This type, as the name suggests, will not affect multiple organs of the body; it affects the localized areas such as the bladder, throat, skin, etc.
What Is the Etiology of Amyloidosis?
The causes of amyloidosis include:
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Hereditary - Hereditary or genetic factors play a major role in hereditary amyloidosis.
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Inflammatory Diseases - Diseases like rheumatoid arthritis and other severe inflammatory conditions contribute to protein misfolding and cause amyloidosis.
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Long-term Dialysis - Patients under dialysis for a long time are at great risk of developing hemodialysis-associated amyloidosis.
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Chronic Diseases or Infection - Studies report that in patients suffering from chronic diseases, infections could develop amyloidosis as it may contribute to protein misfolding.
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Cancer - Cancers affecting the plasma cells and the plasma cell dyscrasias are considered to be one of the important causes of amyloidosis.
What Is the Pathogenesis of Amyloidosis?
The main pathogenesis involved in the development of amyloid deposits is the formation of misfolded proteins in the body. These misfolded proteins or the abnormal proteins produced as a result of above said etiologies would not be metabolized or broken by the normal enzymes because of their abnormal structure. These misfolded proteins start depositing in the organs of the body and form amyloid deposits, which, in turn, affect the organ function and disrupt the architecture of the organs leading to organ damage and progressing to organ failure.
Why Is Amyloidosis Most Common in Kidneys?
Amyloidosis is most commonly associated with the kidneys because the abnormal amyloid proteins secreted in the blood will reach the kidneys for filtration. As the kidneys try to filter these misfolded abnormal proteins, most of them get deposited in the organelles of the kidney as amyloid deposits. These amyloid deposits affect kidney function and result in renal failure.
What Are the Risk Factors for Amyloidosis of the Kidney
The following are the risk factors for developing amyloidosis of the kidney, including:
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Old age.
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Hemodialysis.
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Chronic infection or inflammatory disorder.
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Familial or hereditary link.
What Are the Common Types of Amyloidosis Affecting Kidneys?
The types of amyloidosis that affect kidneys commonly include:
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AL (Amyloid Light Chain) Type - This is the primary type of amyloidosis that affects kidneys predominantly.
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Hemodialysis Associated Amyloidosis - It affects patients who are under long-term dialysis.
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Leukocyte Cell-Derived Chemotaxin2 (LECT2) Amyloidosis - This is a recently recognized type that shows predominant involvement of the kidneys.
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AA (Serum Amyloid A) Amyloidosis - It affects kidneys in patients with chronic infections.
What Is the Pathogenesis of Amyloidosis of the Kidney?
Kidneys are the primary organs involved in removing waste products and extra fluid from the body by a process called filtration. They also reabsorb the essential nutrients, thereby maintaining a balance in the water, salts, and mineral levels in the body. The blood reaches the kidney through a large blood vessel called the renal artery, and then it gets purified by the nephrons. In the case of patients with amyloidosis, the abnormal protein present in the blood will be carried to the kidney for the filtration process. As these abnormal proteins resist breaking down by the enzymes of the body, they will be present as a whole unit in the blood, which is carried to the kidneys. In such cases, kidneys filter a few amyloid proteins, and the rest will start getting deposited in the kidneys, causing deterioration of the renal architecture and affecting kidney function. This, in turn, slowly progresses to permanent damage to the kidney ending up in renal failure.
What Are the Signs And Symptoms of Amyloidosis of the Kidney?
The symptoms indicating deteriorated kidney function as a result of the deposition of amyloid proteins include:
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Heavy Proteinuria - Excessive loss of protein in the urine.
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Edema - Swelling of the hands and foot due to fluid collection in the extracellular space.
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Hypoproteinemia - Decreased serum protein levels due to increased urinary loss of proteins.
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Tingling or Burning sensation - These symptoms occur in the hands and feet.
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Hyperlipidemia - Increased serum cholesterol levels.
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Fatigue or Tiredness - This is caused due to lowering kidney function and increased toxins in the blood.
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Itching - Due to increased urea and creatinine levels in the blood.
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Anemia - Decreased red blood cell count.
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Joint Pain - It may occur in the case of dialysis-related amyloidosis affecting the bones and the joints.
How Is Amyloidosis of the Kidney Diagnosed?
The steps in diagnosis include:
1) Medical and Family History: Medical and family history play an important role in diagnosing the condition as it provides a clue in understanding the symptoms and the genetic link in families.
2) Clinical Examination: Clinical examination of the patient would help to know the signs and symptoms associated with the disease.
3) Blood Test:
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Amyloid Proteins - This would reveal the presence of amyloid proteins in the blood.
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Serum Urea and Creatinine Levels - It may be increased in patients with kidney damage.
4) Kidney Function Test: It is done to check the functional status of the kidneys.
5) Urine Test:
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Proteinuria- Presence of protein in highlevels in the urine.
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Amyloid Proteins - This would reveal the presence of amyloid proteins in the urine.
6) Ultrasound Kidney: The ultrasonographic findings in renal amyloidosis are nonspecific. It may show increased echogenicity and prominence in the medullary pyramids of the kidney.
7) Computed Tomography (CT) Scan or Magnetic Resonance Imaging (MRI): CT scan findings may reveal amorphous renal calcifications or amyloid deposits. MRI may show hypointensity in the affected areas.
8) Kidney Biopsy:
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Light Microscopy - Light microscopic examination of the biopsied tissue would reveal the presence of amorphous eosinophilic hyaline material called amyloid. This amyloid is seen deposited in the mesangium, blood vessels, glomeruli, tubules, and the interstitium of the kidneys disrupting the entire renal architecture.
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Congo Red Staining - This would reveal apple-green birefringence of the amyloid deposits under the polarizing microscope.
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Thioflavin T - Makes the amyloid deposits fluorescent under the fluorescent microscope.
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Silver Stains - This would reveal the presence of spiking along with the glomerular capillary loops.
How Is Amyloidosis of the Kidney Treated?
There is no complete cure for this condition. The main aim of the treatment is to reduce amyloid deposition and to treat the underlying cause of the disease. The methods in treatment include:
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Chemotherapy - Chemotherapy is indicated in patients with cancer conditions, plasma cell dyscrasias, etc., that cause the production of abnormal amyloid proteins. The drugs such as Corticosteroids, alkylating agents, proteasome inhibitors, and immunomodulatory drugs are used to slow down the production and the deposition of amyloid proteins.
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Anti-inflammatory Medications and Antibiotics - Medications such as steroids, non-steroidal anti-inflammatory agents (NSAIDs), and antibiotics can be given to patients with chronic infection and inflammatory disorders.
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Autologous Stem Cell Transplantation - It is indicated in patients with cancer conditions like multiple myeloma, which cause excessive production of monoclonal light chains, causing their deposition in kidneys. In this procedure, the patient's own healthy stem cells are collected before the treatment and then reinjected into the patient's body after treatment. This helps in the production of healthy immunoglobulins and prevents the excessive production of light chains.
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Kidney Transplantation - It is indicated in patients with dialysis-associated amyloidosis and in patients developing renal failure as a complication of amyloidosis.
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Antihypertensives - Medications like Angiotensin-converting enzyme inhibitors or Angiotensin receptor blockers can be given to reduce blood pressure in patients with hypertension caused as a manifestation of renal amyloidosis.
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Diuretics - This may help relieve the symptoms such as edema.
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Iron Supplements - They are given to treat edema.
Conclusion:
Amyloidosis is a group of diseases with the extracellular deposition of a proteinaceous substance called amyloid, affecting many organs. Kidneys are commonly affected by this condition leading to kidney damage and loss of renal function. The prognosis of renal amyloidosis is good if the underlying cause is addressed and treated promptly. In most cases, amyloidosis is not preventable, and there is no complete cure for this condition. Patients with chronic inflammatory disorders or infections should be treated early. In other cases, the main aim of the treatment must be to slow down the progression of the disease and preserve kidney function.