Familial Renal Amyloidosis Treatment & Management

Updated: Nov 10, 2022
  • 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.

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

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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. [33]

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. [42]

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 kidney transplantation alone has been performed for end-stage renal disease in several patients with fibrinogen alpha-chain (AFib) 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 AFib variant, Glu526Val, and younger patients benefit from combined liver and kidney transplantation. [43] A French case series of organ transplantation in 32 patients with AFib amyloidosis reported that recurrence of amyloidosis led to loss of the kidney graft in 33% of patients with the Glu526Val variant but in all the non-Glu526Val variants (eg, residue 544). Amyloid recurrence was not observed in patients after liver-kidney transplantation. [44]

Few examples have been reported, but kidney 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. [26] 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. [45]

Successful liver transplantation has now been reported in hundreds of patients with FAP. 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 liver transplantation, therefore, is potentially curative in patients with fibrinogen A alpha-chain amyloidosis. [43] Simultaneous kidney transplantation is usually required. [46, 47]

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

In the United Kingdom, two patients with apolipoprotein AI amyloidosis have undergone combined heart and kidney transplantation. Both had excellent long term allograft function, surviving 23.1 and 14.9 years after transplantation. [48]

A case report describes retrospective diagnosis of fibrinogen A alpha-chain amyloidosis after combined heart-kidney transplantation. The patient remained well 7 years after transplantation, albeit with recurrence documented in the transplanted kidney and suspected in the transplanted heart. The authors note that if the diagnosis had been made when proteinuria was first discovered, the patient would have been considered for heart-liver or heart-liver-kidney transplantation. [49]

 

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Consultations

If significant extrarenal disease is present, advice should be sought from a gastroenterologist and hepatologist. In the very few patients with cardiac or neurologic involvement, the relevant specialists should be consulted.

Clinical geneticists can provide counseling and advice to family members undergoing screening.

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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.

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