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Familial Renal Amyloidosis Follow-up

  • Author: Helen J Lachmann, MD, MRCP; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
 
Updated: Aug 21, 2015
 

Further Outpatient Care

Ensure regular follow-up care with scrupulous attention to control of blood pressure.

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Deterrence/Prevention

Genetic screening is possible for family members. Adequate counseling is a necessity because the age of onset and penetrance are highly variable and no specific treatment is available.

Prenatal diagnosis is technically possible but is of uncertain value because many individuals with these particular gene mutations have a normal life expectancy.

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Complications

Acute kidney injury and chronic kidney disease can occur in the following forms of familial renal amyloidosis (FRA):

  • FRA due to variant lysozyme
  • FRA due to variant apolipoprotein AI
  • FRA due to variant apolipoprotein AII
  • FRA due to variant fibrinogen A alpha-chain

Acute and chronic liver failure can occur in the following forms of FRA:

  • FRA due to variant apolipoprotein AI
  • Potentially FRA due to variant lysozyme and fibrinogen A alpha-chain (very rarely)

The following complications can occur in these forms of FRA:

  • Restrictive cardiomyopathy - Some apolipoprotein AI and AII variants
  • GI hemorrhage/perforation - Lysozyme FRA
  • Progressive neuropathy - Some patients with apolipoprotein AI Gly26Arg and Leu178His
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Prognosis

Many patients with FRA survive until the seventh decade or older, and most patients survive for at least 10 years after diagnosis. Life expectancy has increased substantially since kidney and liver transplantations have been introduced as treatments for these diseases. Liver transplantation is potentially curative in patients with fibrinogen A alpha-chain FRA and, possibly, in some patients with apolipoprotein AI amyloidosis.

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Patient Education

Patient education should include the following:

  • Patients should be advised to avoid any potential systemic insults such as dehydration, nephrotoxic drugs, and avoidable general anesthetics or surgery.
  • Patients should not only be aware that first-degree relatives each have a 50% chance of carrying the gene but also that disease penetrance is highly variable.
  • For further information, see Mayo Clinic - Kidney Transplant Information.
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Contributor Information and Disclosures
Author

Helen J Lachmann, MD, MRCP Senior Lecturer, Department of Medicine, National Amyloidosis Centre, Royal Free and University College Medical School, England

Helen J Lachmann, MD, MRCP is a member of the following medical societies: Royal College of Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Philip N Hawkins, MBBS, PhD, FRCP Clinical Director of National Amyloidosis Centre, Professor, Department of Medicine, Royal Free and University College Medical School

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

George R Aronoff, MD Director, Professor, Departments of Internal Medicine and Pharmacology, Section of Nephrology, Kidney Disease Program, University of Louisville School of Medicine

George R Aronoff, MD is a member of the following medical societies: American Federation for Medical Research, American Society of Nephrology, Kentucky Medical Association, National Kidney Foundation

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

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Proposed mechanism for amyloid fibril formation. The drawing depicts a generic amyloid fibril precursor protein (I) in equilibrium with a partially unfolded, molten, globulelike form of the protein (II) and its completely denatured state (III). Autoaggregation through the beta domains initiates fibril formation (IV), providing a template for ongoing deposition of precursor proteins and for the development of the stable, mainly beta-sheet, core structure of the fibril. The amyloidogenic precursor proteins in patients with familial renal amyloidosis are thought to be less stable than their wild-type counterparts, causing them to populate intermediate, molten, globulelike states more readily.
An extended kindred with hereditary amyloidosis associated with fibrinogen A alpha-chain Glu526Val; disease penetrance is high in this particular family.
Partial DNA sequence of the gene associated with fibrinogen A alpha-chain Glu526Val in a patient with familial renal amyloidosis, and a sequence from a healthy control. The mutation, which alters codon 526 from glutamic acid to valine, is marked with an arrow.
Progression of amyloid deposits in a patient with amyloidosis associated with fibrinogen A alpha-chain Glu526Val. These serial posterior, whole-body, scintigraphic images were obtained following intravenous injection of iodine-123 (123I)–labeled human serum amyloid P component into a 48-year-old man with hereditary amyloidosis associated with fibrinogen A alpha-chain Glu526Val in whom asymptomatic proteinuria had been identified. Both parents were alive and well and older than age 80 years. The scan at diagnosis (left) showed modest abnormal uptake into renal amyloid deposits, which increased at follow-up 3 years later (right). The remainder of the image represents a normal distribution of tracer throughout the blood pool.
Regression of amyloidosis associated with fibrinogen A alpha-chain Glu526Val following hepatorenal transplantation. The pictures are serial anterior, whole-body, scintigraphic images obtained following intravenous injection of iodine-123 (123I)–labeled human serum amyloid P component into a patient with amyloidosis associated with fibrinogen A alpha-chain Glu526Val. Prior to hepatorenal transplantation (left), heavy amyloid deposition was present in an enlarged liver and spleen. No amyloid deposits were identified in a follow-up study obtained 42 months after hepatorenal transplantation (right); only a normal distribution of tracer is present throughout the blood pool.
Regression of amyloidosis associated with apolipoprotein AI Gly26Arg following hepatorenal transplantation. These serial anterior, whole-body, scintigraphic images were obtained following intravenous injection of iodine-123 (123I)–labeled human serum amyloid P component into a patient with hereditary amyloidosis associated with apolipoprotein AI Gly26Arg. Prior to hepatorenal transplantation (left), heavy amyloid deposition was present in the liver, obscuring the kidneys. Two years after combined hepatorenal transplantation (right), a follow-up scan was normal, showing tracer distributed evenly throughout the background blood pool, including the transplanted organs. Splenic amyloid deposits that were evident initially in posterior scans had regressed at follow-up.
Table. Recognized Genotypes and Their Associated Phenotypes in Familial Renal Amyloidosis
Amyloid Fibril Precursor ProteinOrgans/Tissues Predominantly Affected by Amyloid and Common Clinical FeaturesEthnic Origin of Affected Kindreds
Lysozyme Ile56ThrRenal - Proteinuria and renal failure



Skin - Petechial rashes



Liver and spleen - Organomegaly (usually well-preserved function)



2 British families



(possibly related)



Lysozyme Asp67HisRenal - Proteinuria and renal failure



GI tract - Bleeding and perforation



Liver and spleen - Organomegaly and hepatic hemorrhage



Salivary glands – Sicca syndrome



Single British family
Lysozyme Try64ArgRenal - Proteinuria and renal failure



GI tract - Bleeding and perforation



Salivary glands – Sicca syndrome



Single French family
Apolipoprotein AI



wild type



Amyloid deposits in human aortic atherosclerotic plaques20-30% of elderly individuals at autopsy
Apolipoprotein AI



Gly26Arg



Renal - Proteinuria and renal failure



Gastric mucosa - Peptic ulcers



Peripheral nerves - Progressive neuropathy



Liver and spleen - Organomegaly (usually well-preserved function)



Multiple families



(mostly of northern European extraction)



Apolipoprotein AI



Trp50Arg



Renal - Proteinuria and renal failure



Liver and spleen - Organomegaly and liver failure



Single Ashkenazi family
Apolipoprotein AI



Leu60Arg



Renal - Proteinuria and renal failure



Liver and spleen - Organomegaly (usually well-preserved function)



Cardiac (rarely) - Heart failure



British and



Irish kindreds



Apolipoprotein AI



deletion 60-71



insertion 60-61



Liver - Liver failureSingle Spanish family
Apolipoprotein AI



Leu64Pro



Renal - Proteinuria and renal failure



Liver and spleen - Organomegaly



Single Canadian-Italian family
Apolipoprotein AI



deletion 70-72



Renal - Proteinuria and renal failure



Liver and spleen - Organomegaly (usually well-preserved function)



Retina - Central scotoma



Single family of British origin
Apolipoprotein AI



Leu75Pro



Renal - Proteinuria and



renal failure



Liver and spleen - Organomegaly



Italy – Variable penetrance
Apolipoprotein AI



Leu90Pro



Cardiac - Heart failure



Larynx - Dysphonia



Skin – Infiltrated yellowish plaques



Single French family
Apolipoprotein AI



deletion Lys107



Aortic intima - Aggressive early-onset ischemic heart diseaseSingle Swedish patient at autopsy
Apolipoprotein AI



Arg173Pro



Cardiac - Heart failure



Larynx - Dysphonia



Skin - Acanthosis nigricans-like plaques



British and American families
Apolipoprotein AI



Leu174Ser



Cardiac - Heart failureSingle Italian family
Apolipoprotein AI



Ala175Pro



Larynx - Dysphonia



Testicular - Infertility



Single British family
Apolipoprotein AILeu178HisCardiac - Heart failure



Larynx – Dysphonia



Skin - Infiltrated plaques



Peripheral nerves – Neuropathy



Single French family
Apolipoprotein AII



Stop78Gly



Renal - Proteinuria and renal failureAmerican family
Apolipoprotein AIIStop78SerRenal - Proteinuria and renal failureAmerican family
Apolipoprotein AIIStop78ArgRenal - Proteinuria and renal failureRussian family, Spanish family(different nucleotide substitutions in the two kindreds)
Fibrinogen A alpha-chain Arg554LeuRenal - Proteinuria and renal failurePeruvian,



African American and



French families



Fibrinogen A alpha-chain



frame shift at codon 522



Renal - Proteinuria and renal failureSingle French family
Fibrinogen A alpha-chain



frame shift at codon 524



Renal - Proteinuria and renal failureSingle American family
Fibrinogen A alpha-chain Glu526ValRenal - Proteinuria and renal failure



Late-onset liver (rarely) - Organomegaly and liver failure



Multiple families



(northern European extraction,



variable penetrance)



Fibrinogen A alpha-chain Gly540ValRenal - Proteinuria and renal failureSingle German family
Fibrinogen A alpha-chain Indel 517-522Renal - Proteinuria and renal failureSingle Korean child
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