Further Outpatient Care

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

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.

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

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.

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.

Questions

Bustamante JG, Brito D. Amyloidosis. 2018 Jan. [Medline]. [Full Text].
Ostertag B. Demonstration einer eigenartigen familiaren paraamyloidose. Zentralbl Aug Pathol. 1932. 56:253-4.
Benson MD, Liepnieks J, Uemichi T, et al. Hereditary renal amyloidosis associated with a mutant fibrinogen alpha- chain. Nat Genet. 1993 Mar. 3(3):252-5. [Medline].
Booth DR, Tan SY, Booth SE, et al. A new apolipoprotein Al variant, Trp50Arg, causes hereditary amyloidosis. QJM. 1995 Oct. 88(10):695-702. [Medline].
Booth DR, Tan SY, Booth SE, et al. Hereditary hepatic and systemic amyloidosis caused by a new deletion/insertion mutation in the apolipoprotein AI gene. J Clin Invest. 1996 Jun 15. 97(12):2714-21. [Medline].
de Sousa MM, Vital C, Ostler D, et al. Apolipoprotein AI and transthyretin as components of amyloid fibrils in a kindred with apoAI Leu178His amyloidosis. Am J Pathol. 2000 Jun. 156(6):1911-7. [Medline].
Gillmore JD, Booth DR, Madhoo S, et al. Hereditary renal amyloidosis associated with variant lysozyme in a large English family. Nephrol Dial Transplant. 1999 Nov. 14(11):2639-44. [Medline].
Hamidi Asl K, Liepnieks JJ, Nakamura M, et al. A novel apolipoprotein A-1 variant, Arg173Pro, associated with cardiac and cutaneous amyloidosis. Biochem Biophys Res Commun. 1999 Apr 13. 257(2):584-8. [Medline].
Hamidi Asl L, Fournier V, Billerey C, et al. Fibrinogen A alpha chain mutation (Arg554 Leu) associated with hereditary renal amyloidosis in a French family. Amyloid. 1998 Dec. 5(4):279-84. [Medline].
Hamidi Asl L, Liepnieks JJ, Hamidi Asl K, et al. Hereditary amyloid cardiomyopathy caused by a variant apolipoprotein A1. Am J Pathol. 1999 Jan. 154(1):221-7. [Medline].
Hamidi Asl L, Liepnieks JJ, Uemichi T, et al. Renal amyloidosis with a frame shift mutation in fibrinogen aalpha- chain gene producing a novel amyloid protein. Blood. 1997 Dec 15. 90(12):4799-805. [Medline].
Jones LA, Harding JA, Cohen AS. New USA family has apolipoprotein AI (Arg26) variant. Amyloid and Amyloidosis. 1991. 385-8.
Obici L, Bellotti V, Mangione P, et al. The new apolipoprotein A-I variant leu(174) --> Ser causes hereditary cardiac amyloidosis, and the amyloid fibrils are constituted by the 93- residue N-terminal polypeptide. Am J Pathol. 1999 Sep. 155(3):695-702. [Medline].
Persey MR, Booth DR, Booth SE. A new deletion mutation of the apolipoprotein AI gene causing hereditary amyloidosis. Clin Sci. 1996. 90 (Suppl 34):33.
Persey MR, Booth DR, Booth SE, et al. Hereditary nephropathic systemic amyloidosis caused by a novel variant apolipoprotein A-I. Kidney Int. 1998 Feb. 53(2):276-81. [Medline].
Soutar AK, Hawkins PN, Vigushin DM, et al. Apolipoprotein AI mutation Arg-60 causes autosomal dominant amyloidosis. Proc Natl Acad Sci U S A. 1992 Aug 15. 89(16):7389-93. [Medline].
Uemichi T, Liepnieks JJ, Alexander F, Benson MD. The molecular basis of renal amyloidosis in Irish-American and Polish- Canadian kindreds. QJM. 1996 Oct. 89(10):745-50. [Medline].
Uemichi T, Liepnieks JJ, Benson MD. Hereditary renal amyloidosis with a novel variant fibrinogen. J Clin Invest. 1994 Feb. 93(2):731-6. [Medline].
Uemichi T, Liepnieks JJ, Gertz MA, Benson MD. Fibrinogen A alpha chain Leu 554: an African-American kindred with late onset renal amyloidosis. Amyloid. 1998 Sep. 5(3):188-92. [Medline].
Uemichi T, Liepnieks JJ, Yamada T, et al. A frame shift mutation in the fibrinogen A alpha chain gene in a kindred with renal amyloidosis. Blood. 1996 May 15. 87(10):4197-203. [Medline].
Li Z, Xu H, Liu D, Li D, Liu G, Wang SX. Hereditary renal amyloidosis with a variant lysozyme p.Trp82Arg in a Chinese family: case report and literature review. BMC Nephrol. 2019 Aug 8. 20 (1):310. [Medline]. [Full Text].
Hawkins PN, Myers MJ, Epenetos AA, et al. Specific localization and imaging of amyloid deposits in vivo using 123I-labeled serum amyloid P component. J Exp Med. 1988 Mar 1. 167(3):903-13. [Medline].
Nienhuis HL, Bijzet J, Hazenberg BP. The Prevalence and Management of Systemic Amyloidosis in Western Countries. Kidney Dis (Basel). 2016 Apr. 2 (1):10-9. [Medline]. [Full Text].
Said SM, Sethi S, Valeri AM, Chang A, Nast CC, Krahl L, et al. Characterization and outcomes of renal leukocyte chemotactic factor 2-associated amyloidosis. Kidney Int. 2014 Aug. 86(2):370-7. [Medline].
Castano E, Palmer MB, Vigneault C, Luciano R, Wong S, Moeckel G. Comparison of amyloid deposition in human kidney biopsies as predictor of poor patient outcome. BMC Nephrol. 2015 Apr 29. 16:64. [Medline].
Larsen CP, Kossmann RJ, Beggs ML, Solomon A, Walker PD. Clinical, morphologic, and genetic features of renal leukocyte chemotactic factor 2 amyloidosis. Kidney Int. 2014 Aug. 86(2):378-82. [Medline].
Picken MM. Alect2 amyloidosis: primum non nocere (first, do no harm). Kidney Int. 2014 Aug. 86(2):229-32. [Medline].
von Hutten H, Mihatsch M, Lobeck H, et al. Prevalence and origin of amyloid in kidney biopsies. Am J Surg Pathol. 2009 Aug. 33(8):1198-205. [Medline].
Toros AB, Erdenen F, Sari ND, Gokcay S. Renal and suprarenal insufficiency secondary to familial Mediterranean fever associated with amyloidosis: a case report. J Med Case Reports. 2011 Aug 18. 5(1):390. [Medline]. [Full Text].
Andronesi AG, Ismail G, Gherghiceanu M, Mitroi G, Hârza MC. Familial Mediterranean fever-associated renal amyloidosis: case report and review of the literature. Rom J Morphol Embryol. 2019. 60 (4):1299-1303. [Medline]. [Full Text].
Benson MD, Liepnieks JJ, Yazaki M, Yamashita T, Hamidi Asl K, Guenther B, et al. A new human hereditary amyloidosis: the result of a stop-codon mutation in the apolipoprotein AII gene. Genomics. 2001 Mar 15. 72 (3):272-7. [Medline].
Talamo G, Mir Muhammad A, Pandey MK, Zhu J, Creer MH, Malysz J. Estimation of Daily Proteinuria in Patients with Amyloidosis by Using the Protein-To-Creatinine ratio in Random Urine Samples. Rare Tumors. 2015 Feb 11. 7 (1):5686. [Medline].
Purysko AS, Westphalen AC, Remer EM, Coppa CP, Leão Filho HM, Herts BR. Imaging Manifestations of Hematologic Diseases with Renal and Perinephric Involvement. Radiographics. 2016 Jul-Aug. 36 (4):1038-54. [Medline]. [Full Text].
Barreiros AP, Otto G, Ignee A, et al. Sonographic signs of amyloidosis. Z Gastroenterol. 2009 Aug. 47(8):731-9. [Medline].
Hawkins PN. Studies with radiolabelled serum amyloid P component provide evidence for turnover and regression of amyloid deposits in vivo. Clin Sci (Colch). 1994 Sep. 87(3):289-95. [Medline].
Rydh A, Suhr O, Hietala SO, et al. Serum amyloid P component scintigraphy in familial amyloid polyneuropathy: regression of visceral amyloid following liver transplantation. Eur J Nucl Med. 1998 Jul. 25(7):709-13. [Medline].
Puchtler H, Sweat F, Levine M. On the binding of Congo red by amyloid. J Histochem Cytochem. 1962. 10:355-64.
Sethi S, Vrana JA, Theis JD, Leung N, Sethi A, Nasr SH, et al. Laser microdissection and mass spectrometry-based proteomics aids the diagnosis and typing of renal amyloidosis. Kidney Int. 2012 Apr 11. [Medline].
Picken MM. Proteomics and mass spectrometry in the diagnosis of renal amyloidosis. Clin Kidney J. 2015 Dec. 8 (6):665-72. [Medline]. [Full Text].
Sherif AM, Refaie AF, Sobh MA. Long-term outcome of live donor kidney transplantation for renal amyloidosis. Am J Kidney Dis. 2003 Aug. 42(2):370-5. [Medline].
Gillmore JD, Booth DR, Rela M, et al. Curative hepatorenal transplantation in systemic amyloidosis caused by the Glu526Val fibrinogen alpha-chain variant in an English family. QJM. 2000 May. 93(5):269-75. [Medline].
Holmgren G, Ericzon BG, Groth CG, et al. Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosis. Lancet. 1993 May 1. 341(8853):1113-6. [Medline].
Stangou AJ, Banner NR, Hendry BM, Rela M, Portmann B, Wendon J, et al. Hereditary fibrinogen A alpha-chain amyloidosis: phenotypic characterization of a systemic disease and the role of liver transplantation. Blood. 2010 Apr 15. 115 (15):2998-3007. [Medline].
Zeldenrust S, Gertz M, Uemichi T. Orthotopic liver transplantation for hereditary fibrinogen amyloidosis. Transplantation. 2003 Feb 27. 75(4):560-1. [Medline].
Koike H, Ando Y, Ueda M, et al. Distinct characteristics of amyloid deposits in early- and late-onset transthyretin Val30Met familial amyloid polyneuropathy. J Neurol Sci. 2009 Aug 24. [Medline].
Koike H, Morozumi S, Kawagashira Y, et al. The significance of carpal tunnel syndrome in transthyretin Val30Met familial amyloid polyneuropathy. Amyloid. 2009 Jul 15. 1-7. [Medline].
Amarzguioui M, Mucchiano G, Haggqvist B, et al. Extensive intimal apolipoprotein A1-derived amyloid deposits in a patient with an apolipoprotein A1 mutation. Biochem Biophys Res Commun. 1998 Jan 26. 242(3):534-9. [Medline].

Media Gallery

Familial renal amyloidosis. Proposed mechanism for amyloid fibril formation. The drawing depicts a generic amyloid fibril precursor protein (1) in equilibrium with a partially unfolded, molten, globulelike form of the protein (2) and its completely denatured state (3). Autoaggregation through the beta domains initiates fibril formation (4), providing a template for ongoing deposition of precursor proteins and for the development of the stable, mainly beta-sheet, core structure of the fibril (5). 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.
Familial renal amyloidosis. An extended kindred with hereditary amyloidosis associated with fibrinogen A alpha-chain Glu526Val; disease penetrance is high in this particular family.
Familial renal amyloidosis. 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.
Familial renal amyloidosis. 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.
Familial renal amyloidosis. 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.
Familial renal amyloidosis. 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.

of 6

Table. Recognized Genotypes and Their Associated Phenotypes in Familial Renal Amyloidosis

Table. Recognized Genotypes and Their Associated Phenotypes in Familial Renal Amyloidosis

Amyloid Fibril Precursor Protein	Organs/Tissues Predominantly Affected by Amyloid and Common Clinical Features	Ethnic Origin of Affected Kindreds
Lysozyme Ile56Thr	Renal - Proteinuria and renal failure Skin - Petechial rashes Liver and spleen - Organomegaly (usually well-preserved function)	2 British families (possibly related)
Lysozyme Asp67His	Renal - Proteinuria and renal failure GI tract - Bleeding and perforation Liver and spleen - Organomegaly and hepatic hemorrhage Salivary glands – Sicca syndrome	Single British family
Lysozyme Try64Arg	Renal - Proteinuria and renal failure GI tract - Bleeding and perforation Salivary glands – Sicca syndrome	Single French family
Lysozyme Trp82Arg	Renal - Proteinuria and renal failure	Single Chinese family
Apolipoprotein AI wild type	Amyloid deposits in human aortic atherosclerotic plaques	20-30% 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 failure	Single 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 disease	Single 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 failure	Single Italian family
Apolipoprotein AI Ala175Pro	Larynx - Dysphonia Testicular - Infertility	Single British family
Apolipoprotein AILeu178His	Cardiac - Heart failure Larynx – Dysphonia Skin - Infiltrated plaques Peripheral nerves – Neuropathy	Single French family
Apolipoprotein AII Stop78Gly	Renal - Proteinuria and renal failure	American family
Apolipoprotein AIIStop78Ser	Renal - Proteinuria and renal failure	American family
Apolipoprotein AIIStop78Arg	Renal - Proteinuria and renal failure	Russian family, Spanish family(different nucleotide substitutions in the two kindreds)
Fibrinogen A alpha-chain Arg554Leu	Renal - Proteinuria and renal failure	Peruvian, African American and French families
Fibrinogen A alpha-chain frame shift at codon 522	Renal - Proteinuria and renal failure	Single French family
Fibrinogen A alpha-chain frame shift at codon 524	Renal - Proteinuria and renal failure	Single American family
Fibrinogen A alpha-chain Glu526Val	Renal - Proteinuria and renal failure Late-onset liver (rarely) - Organomegaly and liver failure	Multiple families (northern European extraction, variable penetrance)
Fibrinogen A alpha-chain Gly540Val	Renal - Proteinuria and renal failure	Single German family
Fibrinogen A alpha-chain Indel 517-522	Renal - Proteinuria and renal failure	Single Korean child