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 gastrointestinal 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.
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.
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.
Diuretics
Class Summary
Often help treat symptomatic peripheral edema resulting from nephrotic syndrome.
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.
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.
Omeprazole (Prilosec)
Decreases gastric acid secretion by inhibiting the parietal cell H+/K+ -ATP pump.
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.
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.
Cimetidine (Tagamet)
Inhibits histamine at H2 receptors of gastric parietal cells, which results in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.
Prokinetic agents
Class Summary
Gastric emptying may be delayed, and some patients respond quite well to prokinetic agents or antiemetics.
Metoclopramide (Reglan)
A dopamine antagonist that stimulates gastric emptying and small intestinal transit.
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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.
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Familial renal amyloidosis. An extended kindred with hereditary amyloidosis associated with fibrinogen A alpha-chain Glu526Val; disease penetrance is high in this particular family.
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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.
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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.
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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.
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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.
Tables
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 |
