eMedicine Specialties > Nephrology > The Kidney in Systemic Diseases
Amyloidosis, Familial Renal: Treatment & Medication
Updated: Oct 29, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Organs that are extensively infiltrated by amyloid may fail precipitously, with little or no warning and seemingly without provocation, even when results from routine tests of organ function have previously been entirely normal.
- Scrupulous attention must be paid to blood pressure control, salt and water balance, maintenance of the circulating volume, and prompt treatment of sepsis to reduce the risk of acute organ failure. Elective surgery and general anesthesia are best avoided in patients with systemic amyloidosis, unless compelling indications are present.
- Inexorably progressive organ failure is inevitable, particularly in the case of amyloidotic kidneys, once a certain level of organ dysfunction has occurred. Managing this with hemodialysis or peritoneal dialysis is feasible until a transplant becomes available.
Surgical Care
- Transplantation
- Solid organ transplantation has been used in patients with FRA, chiefly to replace failing renal function, although liver and heart transplants have also been performed.2
- Limited worldwide experience suggests that the vast majority of patients with hereditary renal amyloidosis fare remarkably well with transplantation, and despite continued production of the variant amyloidogenic protein, amyloid deposition within renal grafts is usually slow.
- Kidney transplantation
- This offers most patients with FRA a much improved quality of life and prolonged survival.
- Some patients with variant apolipoprotein AI amyloidosis have had renal grafts for longer than 20 years without any reduction in graft function.
- Isolated renal transplantation alone has been performed for end-stage renal failure in several patients with fibrinogen alpha-chain amyloidosis and probably remains the treatment of choice in older patients with significant co-morbidity. However, clinically significant renal graft amyloid accumulation occurs within a decade in patients with the most common fibrinogen A alpha-chain variant, Glu526Val, and younger patients benefit from combined liver and renal transplantation.
- Few examples have been reported, but renal transplantation may be justified in patients with lysozyme amyloidosis because of its exceptionally slow course and the relative lack of clinical involvement of other organs in patients with this type of FRA.
- Liver transplantation
- This has occasionally been performed for liver failure or acute liver rupture in patients with extensive hepatic amyloidosis. However, clinically significant hepatic amyloidosis is always associated with substantial amyloid deposition in other systems, and transplantation for liver failure, therefore, is palliative unless the production of the respective amyloid fibril precursor protein is reduced.
- Orthotopic liver transplantation has been used widely and successfully as a form of surgical gene therapy in patients with transthyretin-related familial amyloid polyneuropathy (FAP)4,5 because the variant amyloidogenic protein is produced mainly in the liver.
- Successful liver transplantation has now been reported in hundreds of patients with FAP, and, although the peripheral neuropathy usually only stabilizes, autonomic function can improve substantially and the associated visceral amyloid deposits have been shown to regress in many cases.
- Fibrinogen is synthesized solely by the liver, and orthotopic hepatic transplantation, therefore, is potentially curative in patients with fibrinogen A alpha-chain amyloidosis. Simultaneous renal transplantation is usually required.
- Approximately half of the apolipoprotein AI in the circulation is synthesized in the liver, but among the few patients with hereditary apolipoprotein AI amyloidosis who have undergone liver transplantation, it appears that a reduction in the plasma concentration of variant apolipoprotein AI of 50% is sufficient to facilitate overall regression of systemic amyloid deposits.
- Lysozyme is a ubiquitous protein that is produced diffusely within the body, and this type of amyloidosis cannot be ameliorated by liver transplantation.
- Heart transplantation: Two patients with apolipoprotein AI amyloidosis have had successful cardiac transplants.
- One had cardiac amyloidosis associated with apolipoprotein AI Leu174Ser.
- The other presented with severe renal and cardiac involvement resulting from apolipoprotein AI Leu60Arg. This patient was aged 35 years and had a combined cardiac and renal transplant. Ten years later, she had normal functional status with no evidence of amyloid deposition in her grafts.
Consultations
- If significant extrarenal disease is present, advice should be sought from a gastroenterologist and hepatologist.
- In the very few patients with cardiac or neurological involvement, the relevant specialists should be consulted.
- Clinical geneticists can provide counseling and advice to family members undergoing screening.
Medication
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.
Antihypertensive agents
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.
Adult
2.5-5 mg PO qd; not to exceed 20 mg/d
Pediatric
Not established
May increase digoxin, lithium, and allopurinol levels; probenecid may increase levels; coadministration with diuretics increases hypotensive effects; hypotensive effects may be enhanced when given concurrently with diuretics or NSAIDs
Documented hypersensitivity; history of angioedema
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Pregnancy category D in second and third trimesters; caution in renal impairment, valvular stenosis, or severe congestive heart failure
Diuretics
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.
Adult
20-80 mg/d PO/IV/IM; titrate up to 600 mg/d for severe edematous states
Pediatric
Not established
Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently; increased plasma lithium levels and toxicity are possible when taken concurrently
Documented hypersensitivity; hepatic coma, anuria, state of severe electrolyte depletion
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter
Proton pump inhibitors
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.
Adult
20 mg PO qd
Pediatric
Not established
May antagonize effects of metoclopramide; opiate analgesics may increase metoclopramide toxicity in CNS
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Bioavailability may increase in elderly individuals
Histamine2-receptor antagonists
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.
Adult
150 mg PO qd or bid
Pediatric
Not established
May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment
Cimetidine (Tagamet)
Inhibits histamine at H2 receptors of gastric parietal cells, which results in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.
Adult
150 mg PO qid; not to exceed 600 mg/d; 50 mg/dose IV/IM q6-8h; not to exceed 400 mg/d
Pediatric
Not established
Can increase blood levels of theophylline, warfarin, TCAs, triamterene, phenytoin, quinidine, propranolol, metronidazole, procainamide, and lidocaine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Elderly individuals may experience confused states; may cause impotence and gynecomastia in young males; may increase levels of many drugs; adjust dose or discontinue treatment if changes in renal function occur
Prokinetic agents
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.
Adult
5-10 mg PO or 5-20 mg IV/IM tid
Pediatric
Not established
Opiate analgesics may increase toxicity in CNS; levodopa may antagonize effects
Documented hypersensitivity; pheochromocytoma; GI hemorrhage, obstruction, or perforation; history of seizure disorders
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in history of mental illness and Parkinson disease
More on Amyloidosis, Familial Renal |
| Overview: Amyloidosis, Familial Renal |
| Differential Diagnoses & Workup: Amyloidosis, Familial Renal |
 Treatment & Medication: Amyloidosis, Familial Renal |
| Follow-up: Amyloidosis, Familial Renal |
| Multimedia: Amyloidosis, Familial Renal |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
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].
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].
Barreiros AP, Otto G, Ignee A, et al. Sonographic signs of amyloidosis. Z Gastroenterol. Aug 2009;47(8):731-9. [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. Aug 24 2009;[Medline].
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].
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].
Benson MD. Ostertag revisited: the inherited systemic amyloidoses without neuropathy. Amyloid. Jun 2005;12(2):75-87.
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].
Booth DR, Bellotti V, Sunde M. Molecular mechanisms of amyloid fibril formation: the lysozyme model. Clin Sci. 1996;90 (Suppl 34):1P.
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
Jones LA, Harding JA, Cohen AS. New USA family has apolipoprotein AI (Arg26) variant. Amyloid and Amyloidosis. 1991;385-8.
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].
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].
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].
Ostertag B. Demonstration einer eigenartigen familiaren paraamyloidose. Zentralbl Aug Pathol. 1932;56:253-4.
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].
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. Feb 1998;53(2):276-81. [Medline].
Puchtler H, Sweat F, Levine M. On the binding of Congo red by amyloid. J Histochem Cytochem. 1962;10:355-64.
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].
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].
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].
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].
Uemichi T, Liepnieks JJ, Benson MD. Hereditary renal amyloidosis with a novel variant fibrinogen. J Clin Invest. Feb 1994;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. Sep 1998;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. May 15 1996;87(10):4197-203. [Medline].
Zeldenrust S, Gertz M, Uemichi T. Orthotopic liver transplantation for hereditary fibrinogen amyloidosis. Transplantation. Feb 27 2003;75(4):560-1. [Medline].
Further Reading
Clinical trials:
Open-Label Safety and Efficacy Evaluation of Fx-1006A in Patients With Transthyretin Amyloidosis
Radioimmunoimaging of AL Amyloidosis
Study of Systemic Amyloidosis Presentation and Prognosis
The Effect of Diflunisal on Familial Amyloidosis
Transthyretin-Associated Amyloidoses Outcomes Survey (THAOS)
Keywords
familial renal amyloidosis, amyloidosis, amyloid, familial amyloidosis, amyloidosis cardiac, amyloidosis disease, familial systemic amyloidosis, hereditary nonneuropathic amyloidosis, hereditary systemic amyloidosis, hereditary renal amyloidosis, Ostertag-type amyloidosis, apolipoprotein A-I amyloidosis, lysozyme amyloidosis, fibrinogen A alpha-chain amyloidosis
