What are the other Names for this Condition? (Also known as/Synonyms)

• Amyloidosis of Kidney
• Amyloidosis-Associated Kidney Disease
• Kidney Amyloidosis

What is Renal Amyloidosis? (Definition/Background Information)

• Amyloidosis is a group of disorders in which the ‘amyloid protein’ builds up in many organs and tissues of the body. The term “amyloid” is used for protein molecules of any type that stick together owing to misfolding (or incorrect formation of the proteins)
• These protein aggregates are abnormally-formed and arranged into fibrils (slender fibers). An amyloid build-up can occur locally in only one organ, or may occur throughout the body. When the amyloid proteins get deposited in the kidneys, the resulting condition is known as Renal Amyloidosis
• Renal Amyloidosis typically affects older men and women. In general, males are more susceptible to developing the condition than females
• There are 5 major types of amyloidosis including amyloid light amyloidosis, AA amyloidosis, hereditary amyloidosis, wild-type ATTR amyloidosis, and dialysis-related amyloidosis. Renal Amyloidosis can develop in any one of the subtypes of amyloidosis
• The disorder may present with symptoms of excess protein in urine, edema, and recurrent kidney problems. In the hereditary form of amyloidosis, amyloid build-up primarily affects the kidneys and nerves
• Renal Amyloidosis can lead to kidney failure and end-stage kidney disease (ESKD). Kidney transplantation may offer a measure of relief from symptoms and delay progression of the condition. however, the overall prognosis is unpredictable

Who gets Renal Amyloidosis? (Age and Sex Distribution)

• Renal Amyloidosis is common among AA and AL subtypes of amyloidosis and less frequent in other subtypes
• Although all age groups are vulnerable, Renal Amyloidosis affects older adults more frequently. Both male and female genders are affected
• Men are more vulnerable to various subtypes of amyloidosis; therefore, it is possible that Renal Amyloidosis occurs more in men than women

What are the Risk Factors for Renal Amyloidosis? (Predisposing Factors)

The following are some known risk factors for developing Renal Amyloidosis:

• Advancing age
• Male gender
• A family history of Amyloidosis
• Conditions that affect the antibody-producing cells in the body such as:
  • Benign monoclonal gammopathy
  • Malignant lymphoma
  • Multiple myeloma
• Chronic infections such as:
  • Leprosy
  • Bronchiectasis
  • Osteomyelitis
  • Skin infections (in drug abusers who use needles to inject themselves)
  • Chronic infection in skin with burns
  • Chronic kidney infections (pyelonephritis)
  • Whipple’s disease
  • Tuberculosis
• Long-term kidney dialysis
• Certain chronic inflammatory conditions such as:
  • Arthritis - including rheumatoid arthritis, juvenile inflammatory arthritis, psoriatic arthritis, and ankylosing spondylitis
  • Inflammatory bowel disease and ulcerative colitis
  • Uncontrolled diabetes
  • Infectious diseases such as HIV infection and AIDS
  • Cystic fibrosis (individuals with this disease are prone to repeated infections)
• Certain malignancies such as Hodgkin’s lymphoma and renal cell carcinoma
• Having a family history of certain hereditary disorders:
  • Familial Mediterranean fever (FMF)
  • Tumor necrosis factor (TNF) receptor associated periodic syndrome (TRAPS)
  • Hyper immunoglobulin D syndrome and periodic fever syndrome (HIDS)
  • Cryopyrin associated periodic syndrome (CAPS)
  • Majeed syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Renal Amyloidosis? (Etiology)

• Renal Amyloidosis is caused by abnormal amyloid protein deposit and it may occur in any subtype of amyloidosis such as:
  • AA amyloidosis
  • AL amyloidosis
  • Hereditary amyloidosis
  • Wild-type ATTR amyloidosis
  • Dialysis-related amyloidosis
• The amyloid protein fibrils circulate in the bloodstream and get deposited in the kidneys
• The manifestation of Renal Amyloidosis symptoms is clinically significant in AA and AL types of amyloidosis. Symptoms may become apparent in the other subtypes as well

What are the Signs and Symptoms of Renal Amyloidosis?

The signs and symptoms of Renal Amyloidosis may vary among the affected individuals in type and severity. Some individuals may have amyloid deposits in their kidneys without any adverse effect on the organ, while others may exhibit clinically significant symptoms.

Some known signs and symptoms of Renal Amyloidosis include the following:

• Anemia
• Fatigue
• Unintended weight loss
• Excess protein (albumin) in urine
• Decreased amounts of albumin protein in blood
• Lowering of blood pressure
• Hyperlipidemia or increased amount of fat (cholesterol) in blood
• Edema (swelling) is observed in hands, feet, legs and face
• Joint stiffness
• Bone cysts
• Tingling sensation
• Numbness
• Carpal tunnel syndrome that can result in a weak grip
• Blood clot (thrombosis) in the renal vein
• Recurrent kidney problems
• Kidney failure

Since Renal Amyloidosis may be a manifestation of systemic amyloidosis, other signs and symptoms pertinent to specific organ systems may be present. The following are some general symptoms associated with systemic amyloidosis:

• Fatigue
• Swelling in the ankles and legs
• Unintended weight loss
• Pain in hands and feet
• Joint pain
• Skin rashes, which may be purple or red spots
• Rashes around the eyes
• Eyes that appear puffy
• Tingling sensation
• Numbness
• Anemia
• Clay-colored stools
• Bleeding disorders; problems with proper clotting of blood

How is Renal Amyloidosis Diagnosed?

The diagnosis of Renal Amyloidosis may include general tests to ascertain the subtype of amyloidosis (and its underlying cause), as well as specific tests to assess damage to the structure and function of kidneys.

The following methods may be employed for an accurate diagnosis of Renal Amyloidosis:

• A thorough physical examination
• Evaluation of personal and family medical history
• Assessment of the presenting signs and symptoms
• Blood tests:
  • To assess abnormal antibodies
  • For checking heart function (cardiac biomarkers for stress on the heart)
  • To perform “Freelite assay”, a measurement of light chain immunoglobulins
  • For measuring immunoglobulin by immunofixation electrophoresis
  • Liver function test
• Urine tests to check function of kidneys:
  • To check for excess protein (a 24-hour urine test is usually done)
  • To measure immunoglobulin by immunofixation electrophoresis
• Electrocardiography and echocardiography for checking heart functions
• Imaging tests, to assess amyloid deposits in the body/organs, and to assess damage to the organs, tissues, and bones, which include:
  • X-rays
  • Ultrasound imaging
  • Computed tomography scanning
  • Magnetic resonance imaging
  • Serum amyloid protein (SAP) scintigraphy scan: In this procedure, a small amount of radiolabeled (radioactive iodine) SAP is introduced through injection into the body. After several hours, individuals are scanned with a whole body gamma scanner to check for amyloid deposits in the tissues and organs. Individuals undergoing this procedure ingest potassium iodide before and after the procedure, to prevent the thyroid glands from absorbing the radioactive iodine
• Tissue biopsy: A biopsy of the affected kidney is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy sample under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy sample under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis. In case of Renal Amyloidosis,
  • Immunohistochemical analysis of tissue samples using anti-AA serum may be performed, to identify the type of amyloidosis an individual has
  • Biopsy of affected tissue such as organ tissue, bone, muscle, or fat, if necessary
  • Amyloid deposit from affected tissue is detected using a staining procedure. When stained with Congo red stain, the amyloid protein deposits appear green under a special type of microscope (polarizing microscope)
  • Bone marrow aspiration for checking the type of abnormal immunoglobulin light chains
• Molecular genetic testing to check for mutation(s) in the TTR gene, which is the most common gene involved in hereditary amyloidosis
• Molecular testing to check the type of proteins in amyloid deposits (AL or AA chains) through mass spectrophotometry

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Renal Amyloidosis?

The potential complications of Renal Amyloidosis include:

• Increased susceptibility to infections
• Stiffness and pain in joints leading to difficulty with joint movement
• Bone fractures due to formation of bone cysts
• Dizziness and risks of fall, when one stands too quickly from a seated position
• Kidney failure, resulting in end-stage renal disease (ESRD)

How is Renal Amyloidosis Treated?

Currently, there are no treatment options available to cure Renal Amyloidosis. However, treatment is available to ease the symptoms and slow disease progression. The treatment measures are unique to each affected individual and are dictated by the extent of kidney damage. These include:

• Diet: Having frequent and small meals through the day, with reduced fat and sodium content
• Effective management of a pre-existing condition that resulted in amyloidosis
• Restricting fluid intake, if there is edema
• Moderate exercise
• Diuretics to get rid of excess salt and water from the body
• Use of Lixelle “beta 2-microglobulin apheresis column” for dialysis-induced amyloidosis. This device removes beta-2 microglobulin from blood
• Use of better filters for the dialysis apparatus in dialysis-related amyloidosis
• Dialysis in case of kidney failure
• Kidney transplantation for kidney failure

It must be noted that Renal Amyloidosis does not occur in isolation and can be systemic, affecting multiple organs at the same time. Therefore, additional treatments pertaining to the subtype of amyloidosis and its underlying cause are often necessary.

How can Renal Amyloidosis be Prevented?

• Currently, there are no specific methods or guidelines to prevent Renal Amyloidosis
• If there is a family history of amyloidosis, then genetic counseling will help assess risks, before planning for a child
• Seeking medical attention for pre-existing conditions that can lead to amyloidosis, which consequently causes Renal Amyloidosis is advisable
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

What is the Prognosis of Renal Amyloidosis? (Outcomes/Resolutions)

• The prognosis for Renal Amyloidosis may be determined by a number of factors, such as the extent of the condition and overall health of the affected individual
• If treatment is delayed, Renal Amyloidosis can be a life-threatening condition
• The quality of life may be affected, owing to the various symptoms and problems with movement
• Potentially severe cases of Renal Amyloidosis may require kidney transplantation

Additional and Relevant Useful Information for Renal Amyloidosis:

• Approximately, 30 different proteins with a tendency to form amyloids have been identified. These are known as precursor proteins or amyloidogenic proteins
• The misfolding of proteins can occur due to a number of reasons, including aberrant formation, improper breakdown, or accumulation beyond a critical concentration in serum