Familial Renal Amyloidosis Medication

  • Author: Helen J Lachmann, MB, MA, MD, MRCP; Chief Editor: Vecihi Batuman, MD, FACP, FASN   more...
 
Updated: May 1, 2012
 

Medication Summary

The aims of current medical therapy are to support compromised organ function and to ameliorate symptoms.

Patients are at increased risk of hemorrhage because of increased vascular fragility and/or substantial GI amyloid deposits. Unless overwhelming indications for anticoagulation therapy are present, it is best avoided.

No existing treatment specifically results in mobilization and regression of amyloid deposits, but novel drug compounds that inhibit the formation, persistence, and/or effects of amyloid deposits are presently in development.

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Antihypertensive agents

Class Summary

Hypertension is common and can accelerate the decline in renal function. Maintain blood pressure within the lower end of normal range.

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Ramipril (Altace)

 

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

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Diuretics

Class Summary

Often help treat symptomatic peripheral edema resulting from nephrotic syndrome.

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Furosemide (Lasix)

 

Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Dose must be individualized to patient. Depending on response, administer at increments of 20-40 mg, no sooner than 6-8 h after previous dose, until desired diuresis occurs.

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Proton pump inhibitors

Class Summary

Acute GI bleeding or perforation is the cause of death in a large proportion of patients with lysozyme amyloidosis, and long-term prophylactic treatment with a proton pump inhibitor is advisable.

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Omeprazole (Prilosec)

 

Decreases gastric acid secretion by inhibiting the parietal cell H+/K+ -ATP pump.

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Histamine2-receptor antagonists

Class Summary

Reversible competitive blockers of histamine at the H2 receptors, particularly those in the gastric parietal cells, where they inhibit acid secretion. The H2 antagonists are highly selective, do not affect the H1 receptors, and are not anticholinergic agents.

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Ranitidine (Zantac)

 

Inhibits histamine stimulation of the H2 receptor in gastric parietal cells, which, in turn, reduces gastric acid secretion, gastric volume, and hydrogen concentrations.

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Cimetidine (Tagamet)

 

Inhibits histamine at H2 receptors of gastric parietal cells, which results in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.

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Prokinetic agents

Class Summary

Gastric emptying may be delayed, and some patients respond quite well to prokinetic agents or antiemetics.

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Metoclopramide (Reglan)

 

A dopamine antagonist that stimulates gastric emptying and small intestinal transit.

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Contributor Information and Disclosures
Author

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

Helen J Lachmann, MB, MA, 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

Donald A Feinfeld, MD, FACP, FASN  Consulting Staff, Division of Nephrology & Hypertension, Beth Israel Medical Center

Donald A Feinfeld, MD, FACP, FASN is a member of the following medical societies: American Academy of Clinical Toxicology, American Society of Hypertension, American Society of Nephrology, and National Kidney Foundation

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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, and National Kidney Foundation

Disclosure: Nothing to disclose.

Rebecca J Schmidt, DO, FACP, FASN  Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine

Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association

Disclosure: Renal Ventures Ownership interest Other

Chief Editor

Vecihi Batuman, MD, FACP, FASN  Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, 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, and International Society of Nephrology

Disclosure: Nothing to disclose.

References

  1. von Hutten H, Mihatsch M, Lobeck H, et al. Prevalence and origin of amyloid in kidney biopsies. Am J Surg Pathol. Aug 2009;33(8):1198-205. [Medline].

  2. Yilmaz G, Masatlioglu S, Yetkin DO, Demirtunç R, Boysan SN, Kaplan S, et al. Is there a real adrenal axis dysfunction in patients with amyloidosis associated with familial Mediterranean fever?. Rheumatol Int. Nov 6 2011;[Medline].

  3. 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. Aug 18 2011;5(1):390. [Medline]. [Full Text].

  4. Stangou AJ, Banner NR, Hendry BM, et al. Hereditary fibrinogen A {alpha}-chain amyloidosis: phenotypic characterization of a systemic disease and the role of liver transplantation. Blood. Jul 24 2009;[Medline].

  5. Barreiros AP, Otto G, Ignee A, et al. Sonographic signs of amyloidosis. Z Gastroenterol. Aug 2009;47(8):731-9. [Medline].

  6. 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. Apr 11 2012;[Medline].

  7. Ozturk MA, Kanbay M, Kasapoglu B, Onat AM, Guz G, Furst DE, et al. Therapeutic approach to familial Mediterranean fever: a review update. Clin Exp Rheumatol. Jul-Aug 2011;29(4 Suppl 67):S77-86. [Medline].

  8. 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. Aug 24 2009;[Medline].

  9. Koike H, Morozumi S, Kawagashira Y, et al. The significance of carpal tunnel syndrome in transthyretin Val30Met familial amyloid polyneuropathy. Amyloid. Jul 15 2009;1-7. [Medline].

  10. 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. Jan 26 1998;242(3):534-9. [Medline].

  11. Benson MD. Ostertag revisited: the inherited systemic amyloidoses without neuropathy. Amyloid. Jun 2005;12(2):75-87.

  12. Benson MD, Liepnieks J, Uemichi T, et al. Hereditary renal amyloidosis associated with a mutant fibrinogen alpha- chain. Nat Genet. Mar 1993;3(3):252-5. [Medline].

  13. Booth DR, Bellotti V, Sunde M. Molecular mechanisms of amyloid fibril formation: the lysozyme model. Clin Sci. 1996;90 (Suppl 34):1P.

  14. Booth DR, Sunde M, Bellotti V, et al. Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis. Nature. Feb 27 1997;385(6619):787-93. [Medline].

  15. Booth DR, Tan SY, Booth SE, et al. A new apolipoprotein Al variant, Trp50Arg, causes hereditary amyloidosis. QJM. Oct 1995;88(10):695-702. [Medline].

  16. 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. Jun 15 1996;97(12):2714-21. [Medline].

  17. 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. Jun 2000;156(6):1911-7. [Medline].

  18. Gillmore JD, Booth DR, Madhoo S, et al. Hereditary renal amyloidosis associated with variant lysozyme in a large English family. Nephrol Dial Transplant. Nov 1999;14(11):2639-44. [Medline].

  19. 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. May 2000;93(5):269-75. [Medline].

  20. 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. Apr 13 1999;257(2):584-8. [Medline].

  21. 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. Dec 1998;5(4):279-84. [Medline].

  22. Hamidi Asl L, Liepnieks JJ, Hamidi Asl K, et al. Hereditary amyloid cardiomyopathy caused by a variant apolipoprotein A1. Am J Pathol. Jan 1999;154(1):221-7. [Medline].

  23. 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. Dec 15 1997;90(12):4799-805. [Medline].

  24. Hawkins PN. Studies with radiolabelled serum amyloid P component provide evidence for turnover and regression of amyloid deposits in vivo. Clin Sci (Colch). Sep 1994;87(3):289-95. [Medline].

  25. 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. Mar 1 1988;167(3):903-13. [Medline].

  26. Holmgren G, Ericzon BG, Groth CG, et al. Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosis. Lancet. May 1 1993;341(8853):1113-6. [Medline].

  27. Jones LA, Harding JA, Cohen AS. New USA family has apolipoprotein AI (Arg26) variant. Amyloid and Amyloidosis. 1991;385-8.

  28. Lachmann HJ, Booth DR, Booth SE, et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med. Jun 6 2002;346(23):1786-91. [Medline].

  29. Nichols WC, Dwulet FE, Liepnieks J, Benson MD. Variant apolipoprotein AI as a major constituent of a human hereditary amyloid. Biochem Biophys Res Commun. Oct 31 1988;156(2):762-8. [Medline].

  30. 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. Sep 1999;155(3):695-702. [Medline].

  31. Ostertag B. Demonstration einer eigenartigen familiaren paraamyloidose. Zentralbl Aug Pathol. 1932;56:253-4.

  32. Pepys MB, Hawkins PN, Booth DR, et al. Human lysozyme gene mutations cause hereditary systemic amyloidosis. Nature. Apr 8 1993;362(6420):553-7. [Medline].

  33. 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.

  34. Persey MR, Booth DR, Booth SE, et al. Hereditary nephropathic systemic amyloidosis caused by a novel variant apolipoprotein A-I. Kidney Int. Feb 1998;53(2):276-81. [Medline].

  35. Puchtler H, Sweat F, Levine M. On the binding of Congo red by amyloid. J Histochem Cytochem. 1962;10:355-64.

  36. 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. Jul 1998;25(7):709-13. [Medline].

  37. Sherif AM, Refaie AF, Sobh MA. Long-term outcome of live donor kidney transplantation for renal amyloidosis. Am J Kidney Dis. Aug 2003;42(2):370-5. [Medline].

  38. Soutar AK, Hawkins PN, Vigushin DM, et al. Apolipoprotein AI mutation Arg-60 causes autosomal dominant amyloidosis. Proc Natl Acad Sci U S A. Aug 15 1992;89(16):7389-93. [Medline].

  39. Uemichi T, Liepnieks JJ, Alexander F, Benson MD. The molecular basis of renal amyloidosis in Irish-American and Polish- Canadian kindreds. QJM. Oct 1996;89(10):745-50. [Medline].

  40. Uemichi T, Liepnieks JJ, Benson MD. Hereditary renal amyloidosis with a novel variant fibrinogen. J Clin Invest. Feb 1994;93(2):731-6. [Medline].

  41. Uemichi T, Liepnieks JJ, Gertz MA, Benson MD. Fibrinogen A alpha chain Leu 554: an African-American kindred with late onset renal amyloidosis. Amyloid. Sep 1998;5(3):188-92. [Medline].

  42. 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. May 15 1996;87(10):4197-203. [Medline].

  43. Zeldenrust S, Gertz M, Uemichi T. Orthotopic liver transplantation for hereditary fibrinogen amyloidosis. Transplantation. Feb 27 2003;75(4):560-1. [Medline].

 
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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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