Renal Amyloidosis and Musculoskeletal Changes

Introduction:

Amyloidosis is a group of disorders characterized by extracellular tissue deposition of low molecular weight proteins. The deposition site depends on the type of amyloidosis, which can be hereditary, localized, or systemic. Amyloidosis may develop as a primary disease, secondary to other health conditions, or a hereditary disease. The exact etiology of the condition is unknown. Renal involvement is a common phenomenon in 80 % of patients with amyloidosis, but other organs may be involved. There is no cure for the condition. It is a rare condition in which early diagnosis aids in effective management.

What Are the Causes of Renal Amyloidosis?

Renal amyloidosis occurs due to abnormal amyloid protein fibril deposition in the kidneys. Different kidney areas may be affected, most commonly being glomeruli (filtrating area of the kidney). The symptoms manifest as nephrotic syndrome.

What Is the Pathophysiology of Amyloidosis?

• Overproduction:

The production of precursor proteins increases in several conditions, such as chronic inflammatory disease. Persistent stimulation due to inflammation causes an immune response leading to amyloid protein formation in various organs.

• Decreased Clearance:

Retention of B2 microglobulin causes renal failure. Renal clearance of this protein is decreased, and plasma level is increased.

• Unstable Proteins:

There is a mutation in protein leading to unstable nature. Transthyretin and lysozyme are examples of this condition.

What Are the Types of Renal Amyloidosis With Musculoskeletal Manifestations?

• Al Amyloidosis (Primary Amyloidosis):

Plasma cells in the bone marrow are affected, causing excessive production of light-chain proteins. These damaged proteins, accumulated in the kidney, affect their function. Musculoskeletal manifestations include muscle weakness, pseudohypertrophy joint disorders, and bone lesions (osteopathy). Other organs may be involved. Neoplastic tendencies are common in AL amyloidosis.

• AA Amyloidosis (Secondary or Reactive Amyloidosis):

This condition is caused due to high serum A protein levels due to long-lasting infection or inflammatory disease. This condition commonly affects the kidneys. Secondary amyloidosis is the most common type of amyloidosis. Renal amyloidosis may be associated with rheumatoid arthritis, juvenile idiopathic arthritis, spondylitis, psoriatic arthritis, and osteomyelitis.

• Leukocyte Cell-Derived Chemotaxin 2- Associated (ALECT2):

Recently reported amyloidosis that predominantly affects the kidney. Amyloidosis of this kind most commonly affects Hispanics and Mexicans. It is seen among the elderly with chronic renal insufficiency. Proteinuria may be absent.

• Hereditary Amyloidosis:

It is common in individuals with familial history of the condition. It is caused due to abnormality in the transthyretin protein. Symptoms include hyperesthesia to pain and temperature, motor weakness, weight loss, and diminished deep tendon reflexes.

• Dialysis-Related Amyloidosis:

Long-term regular hemodialysis for chronic renal failure is associated with amyloidosis. As a result, B2 microglobulin is commonly accumulated in the kidney.

What Is Amyloidosis in Pediatric Patients?

Juvenile idiopathic arthritis is the most common arthritis. It is associated with secondary amyloidosis and is a serious and fatal complication. The symptoms developed include bone pain, joint stiffness, fever, etc.

What Are the Symptoms of Renal Amyloidosis?

• Asymptomatic proteinuria (discharge of protein in urine)

• Nephrotic syndrome (foamy urine, fluid retention, etc.).

• Renal failure.

• Edema.

• Anemia.

• High blood pressure.

• Shortness of breath.

• Muscle weakness.

• Swollen tongue with ripples on edges.

• Joint pain (arthritis).

• Weight loss.

• Swelling of hands and feet.

• Tiredness (fatigue).

What Are the Musculoskeletal Manifestations of Dialysis-Related Amyloidosis?

Various musculoskeletal symptoms are seen due to hemodialysis in old-age patients. Excess amounts of unabsorbable plasma protein beta-microglobulin are laid down in tendons, joints, and bones. The symptoms manifest several years after dialysis. The symptoms are joint pain without radiological changes of arthritis, with the shoulder most commonly affected. Carpal tunnel syndrome may be seen. In certain cases, bilateral involvement is seen. Few patients experience relapse after two to three years and may require further decompression. The severity of symptoms depends on the duration of dialysis.

Regions affected include the shoulder, hip, knee, wrist, elbow, ankle, lumbar spine, and cervical spine. Musculoskeletal complications include:

• Carpal tunnel syndrome (numbness or a tingling feeling in the hands and feet) is managed by compression.

• Trigger finger is managed by tendon sheath release.

• Tendon contracture is managed by releasing or strengthening.

• Tendon rupture is repaired.

• Pathological fracture occurring in the hip is treated with hip screws.

• Avascular necrosis of femoral head.

• Radial artery steal syndrome.

Among Children:

• Bilateral gastrocnemius contracture.

• Bilateral genu valgum.

Symptoms That Are Seen in Hereditary Amyloidosis Are:

• Joint pain, swelling, and stiffness.

• Sleep disruption.

• Worsening pain during dialysis.

• Synovial thickening.

• Muscle wasting.

How Is Amyloidosis Diagnosed?

• Medical history and physical examination are crucial in diagnosing the disease.
• Histopathological Examination.
• Biopsy of Kidney.
• All types of amyloid fibrosis appear congo red on microscopic examination and apple-green birefringence under polarized light.
• Lab Diagnosis.
• Urine analysis to detect proteinuria that helps in assessing kidney damage.

What Are the Risk Factors?

• Age - It affects individuals above 50 years of age.

• Sex - Most predominant in men.

• Chronic infections, inflammatory conditions, and autoimmune diseases also cause amyloidosis.

• Family history - Some individuals with a family history develop this condition.

• Kidney dialysis - Long term dialysis may lead to this condition.

What Is the Treatment for Amyloidosis?

There is no specific treatment for the disease. The main aim is to slow the progression, reduce the impact of symptoms and prolong life.

• Chemotherapy:

Certain medicines used in killing cancer cells can aid in halting the growth of cells that make abnormal proteins.

• Bone Marrow Transplant:

After destroying unhealthy cells that produce amyloid with chemotherapy, stem cells from the blood are used to replace the unhealthy cells.

• Medications:

Some of the common drugs used are:

• Steroids are commonly given to increase the effect of chemotherapy.

• Cyclophosphamide.

• Bortezomib.

• Rituximab.

In cases of secondary amyloidosis, the underlying conditions are managed, which aids in resolving amyloidosis.

Supportive Treatment:

• Control of blood pressure with medications.

• Management of end-stage kidney disease with transplantation or dialysis. However, kidney transplantation is not effective in all patients, especially in those with large deposition of amyloid proteins in the kidney.

• Diuretic medications to remove excess water.

• Compression stocking to reduce swelling in legs.

Even after the treatment, the patient should be under follow-up to detect relapse. Relapse cases may require further chemotherapy in such cases.

What Are the Complications of Amyloidosis?

Amyloidosis affects kidneys and harms their filtering functions leading to the accumulation of waste products. The accumulated toxins further lead to kidney failure.

What Is the Prognosis of Amyloidosis?

Early detection enables better treatment outcomes for the condition. Progression to kidney failure can be life-threatening.

Conclusion:

Amyloidosis is a rare condition. Effective management is done by identifying the type of amyloidosis and providing tailored treatment. Early intervention can improve treatment outcomes.