Familial Renal Amyloidosis: An Overview

Introduction:

Amyloidosis is a disorder of protein folding, usually soluble proteins that undergo conformational changes and deposit in the extracellular space in abnormal fibrous form. Accumulation of these fibrils causes progressive damage to the structural and functional abilities of the tissues and organs, and systemic (generalized) amyloidosis is often fatal.

Renal dysfunction is among the most common findings of systemic amyloidosis, and amyloid accumulation is found in approximately 2.5 % of all native renal biopsies. The syndrome of familial systemic amyloidosis with dominant nephropathy was regarded as an autosomal dominant disease and was first reported in a German family and was detailed by Ostertag in 1932.

What Is Familial Renal Amyloidosis?

Familial renal amyloidosis (FRA) is a type of amyloidosis that occurs primarily in the kidneys. It is most commonly associated with congenital mutations in the fibrinogen alpha chain and is classified as abnormal fibrinogenemia (hereditary fibrinogen Aα chain amyloidosis). Rarely, there are congenital mutations in apolipoprotein A1 and lysozyme.

What Causes Familial Renal Amyloidosis?

Sensitivity to FRA is autosomal dominant inheritance. In almost all cases, the disease results from mutations in the genes that encode the following four plasma proteins -

• Lysozyme- It is a ubiquitous lytic enzyme found in both external secretions and white blood cells.

• Apolipoprotein AI- It is the main component of high-density lipoprotein (HDL) particles and is involved in the central function of reverse cholesterol transport from the periphery to the liver.

• Apolipoprotein A-II- It is the second major component of human HDL particles, accounting for about 20 % of HDL protein. Similar to apolipoprotein AI, apolipoprotein AII is synthesized primarily in the liver and intestines.

• Fibrinogen Alpha Chain-Fibrinogen- It is a 340-kd multimeric circulating glycoprotein composed of six peptide chains (two each for alpha, beta, and gamma types) synthesized in the liver.

In some families, the cause has not yet been clarified.

What Are the Symptoms Seen With Familial Renal Amyloidosis?

The symptoms vary from person to person who suffers from familial renal amyloidosis. Some patients may portray more manifestations than others, and the symptoms range from mild to severe. The common signs and symptoms include -

• Decreased Creatinine Clearance- An abnormal decrease in the amount of fluid filtered from plasma through the glomerular capillary wall into Bowman's capsule per unit of time.

• Systemic Hypertension- The presence of chronically elevated pressure in the systemic arterial system.

• Adult Renal Failure- Decreased renal efficiency in functional areas such as urinary levels, waste removal, electrolyte balance maintenance, blood pressure homeostasis, and calcium metabolism.

• Gastric Upset- Discomfort characterized by physical discomfort (stinging, throbbing, pain) that may be caused by the abdomen.

• Lymph Node Abnormalities- Enlargement or defect of lymph nodes.

• Anemia- Decrease in the red blood cell count or hemoglobin count.

• Heart Failure- Fibril deposition in multiple organs, including the heart, kidneys, liver, and peripheral nerves, causes organ dysfunction and associated morbidity and mortality. The most common amyloid fibrous deposits associated with cardiac symptoms are the monoclonal light chain or transthyretin (ATTR) type.

• Diarrhea- Watery stool.

How Is Familial Renal Amyloidosis Diagnosed?

Laboratory tests also play an important role in assessing and monitoring amyloid organ function.

• Urine Test- The protein-creatinine ratio (P/C ratio) in a random urine sample is a study of 44 patients with amyloidosis that strongly correlates with 24-hour urinary protein excretion and is useful for screening renal lesions. There is a possibility.

• Liver Function Test- The results are usually normal until extensive amyloid infiltration into the liver. Even marked hepatomegaly (enlarged liver) may be accompanied by a modest increase in serum alkaline phosphatase. Liver function in FRA patients occurs at a very late stage of elevated serum bilirubin and transaminase levels and is often well-preserved for decades. Bilirubin levels, which are only twice the upper limit of normal levels, are associated with a very poor prognosis and the development of liver failure.

• Imaging- Anatomical diagnostic imaging methods such as X-rays, CT (computed tomography), MRI (magnetic resonance imaging), and ultrasonography) usually produce nonspecific findings in patients with systemic amyloidosis.

• DNA Analysis- It is essential for all patients with systemic amyloidosis who cannot be identified as AA or AL type. It is essential to note that chronic inflammatory disease or monoclonal gammopathy can also be found accidentally.

How Is Renal Amyloidosis Treated?

Organs that are extensively infiltrated with amyloid may suddenly fail because they appear to have little or no warning and no provocation, even if the results of previous routine organ function tests are perfectly normal. Great care must be taken to reduce the risk of acute organ failure -

• Blood Pressure Control- High blood pressure is common and can accelerate the decline in renal function.

• Saltwater Balance- Often helps manage symptomatic peripheral edema due to nephrotic syndrome.

• Maintaining Circulation- Acute gastrointestinal bleeding or perforation is the cause of most deaths in patients with lysozyme amyloidosis, and long-term prophylactic treatment with proton pump inhibitors is recommended.

• Immediate Treatment for Sepsis- Control of infection in the body.

• Surgery- In patients with systemic amyloidosis, it is best to avoid elective surgery and general anesthesia unless there is a compelling indication.

• Dialysis- When some degree of organ dysfunction occurs, relentlessly progressive organ failure is unavoidable, especially in the amyloid kidney. Treatment with hemodialysis or peritoneal dialysis can be performed until transplantation is possible.

• Organ Transplant- Solid organ transplants are performed in patients with FRA. Most were kidney transplants, but liver and heart transplants are also done.

Conclusion:

A group of rare renal diseases characterized by amyloid fibrosis of apolipoprotein A-I or A-II (AApoAI or AApoAII amyloidosis), lysozyme (Alys amyloidosis), or fibrinogen A alpha-chain (AFib amyloidosis) in one or more organs. Kidney involvement leading to chronic kidney disease and renal failure is a common sign. Further symptoms depend on the affected organ and the type of amyloid fibrils deposited. Family genetic screening is possible. Appropriate counseling is required as the age of onset and penetrance vary widely, and there is no specific treatment.

Prenatal testing is technically possible, but its value is uncertain because many individuals with these specific gene mutations have a normal life expectancy. Most patients with FRA survive to age 70 years or older, and most survive at least ten years after diagnosis. Life expectancy has increased significantly since kidney and liver transplants were introduced to treat these diseases. Liver transplantation may cure the disease in patients with fibrinogen A-alpha chain FRA and certain patients suffering from apolipoprotein AI amyloidosis.