Hereditary amyloid nephropathy

=Hereditary Amyloid Nephropathy = Hereditary amyloid nephropathy is a rare genetic disorder characterized by the deposition of amyloid proteins in the kidneys, leading to progressive renal dysfunction. This condition is part of a group of diseases known as amyloidosis, which are caused by the abnormal accumulation of amyloid fibrils in various tissues and organs.

Pathophysiology

The underlying cause of hereditary amyloid nephropathy is the mutation in specific genes that lead to the production of abnormal proteins. These proteins misfold and aggregate into insoluble fibrils, which are deposited in the kidney tissue. Over time, these deposits disrupt normal kidney function, leading to symptoms such as proteinuria, hypertension, and eventually renal failure.

Genetic Mutations

The most common genetic mutations associated with hereditary amyloid nephropathy occur in the transthyretin (TTR) gene, although mutations in other genes such as fibrinogen A alpha-chain (AFib) and apolipoprotein A-I (ApoA-I) have also been implicated. These mutations are typically inherited in an autosomal dominant pattern.

Clinical Presentation

Patients with hereditary amyloid nephropathy often present with symptoms related to kidney dysfunction. Early signs include:

• Proteinuria: Excessive protein in the urine, often detected during routine medical examinations.
• Hypertension: High blood pressure due to impaired kidney function.
• Edema: Swelling in the legs and ankles due to fluid retention.

As the disease progresses, patients may develop chronic kidney disease and eventually end-stage renal disease, requiring dialysis or kidney transplantation.

Diagnosis

Diagnosis of hereditary amyloid nephropathy involves a combination of clinical evaluation, laboratory tests, and genetic analysis. Key diagnostic steps include:

• Urinalysis: To detect proteinuria and other abnormalities.
• Blood tests: To assess kidney function and identify abnormal proteins.
• Kidney biopsy: To confirm the presence of amyloid deposits in kidney tissue.
• Genetic testing: To identify specific mutations in genes associated with the disease.

Treatment

Currently, there is no cure for hereditary amyloid nephropathy, but treatment focuses on managing symptoms and slowing disease progression. Treatment options include:

• Medications: To control blood pressure and reduce proteinuria.
• Lifestyle modifications: Such as dietary changes and regular exercise to support kidney health.
• Dialysis: For patients with advanced kidney failure.
• Kidney transplantation: In selected cases, to replace the damaged kidney.

Prognosis

The prognosis for patients with hereditary amyloid nephropathy varies depending on the specific genetic mutation and the extent of kidney damage at diagnosis. Early detection and management can improve outcomes, but many patients eventually require renal replacement therapy.

Research and Future Directions

Ongoing research is focused on understanding the molecular mechanisms of amyloid formation and developing targeted therapies to prevent or reverse amyloid deposition. Gene therapy and novel pharmacological agents are being explored as potential treatments.

See Also

• Amyloidosis
• Transthyretin amyloidosis
• Renal failure

NIH genetic and rare disease info

• NIH info on Hereditary amyloid nephropathy

Hereditary amyloid nephropathy is a rare disease.