Familial Renal Amyloidosis Treatment & Management

Updated: Nov 21, 2018
  • Author: Helen J Lachmann, MD, MRCP; Chief Editor: Vecihi Batuman, MD, FASN  more...
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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. To reduce the risk of acute organ failure, scrupulous attention must be paid to the following:

  • Blood pressure control
  • Salt and water balance
  • Maintenance of circulating volume
  • Prompt treatment of sepsis

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.

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Surgical Care

Solid organ transplantation has been used in patients with FRA. Most have been kidney transplants, although liver and heart transplants have also been performed. [9]

Kidney transplantation

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. [17]

Kidney transplantation 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

Liver transplantation has occasionally been performed for liver failure or acute liver rupture in patients with extensive hepatic amyloidosis. [4] However, clinically significant hepatic amyloidosis is always associated with substantial amyloid deposition in other systems, so transplantation for liver failure 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) because the variant amyloidogenic protein is produced mainly in the liver. [18]

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. [19, 20]

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 35 years old 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.

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Consultations

See the list below:

  • 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.

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