Solid Organ Transplantation in Amyloidosis

Abstract

Amyloidosis comprises a diverse group of diseases characterized by misfolding of precursor proteins which eventually form amyloid aggregates and preceding intermediaries, which are deposited in target tissues causing progressive organ damage. In all forms of amyloidosis, vital organs may fail; depending on the specific amyloidosis type, this may occur rapidly or progress slowly. Beyond therapies to reduce the precursor protein (chemotherapy for light chain [AL] amyloidosis, anti-inflammatory therapy in serum A amyloidosis [AA], and antisense RNA therapy in transthyretin amyloidosis [ATTR]), organ transplantation may also be a means to reduce amyloidogenic protein, e.g., in types of amyloidosis in which the variant precursor is produced by the liver. Heart transplantation is a life-saving approach to the treatment of patients with advanced cardiac amyloidosis; however, amyloidosis may still be considered a contraindication to the procedure despite data supporting improved outcomes, similar to patients with other indications. Kidney transplantation is associated with particularly favorable outcomes in patients with amyloidosis, especially if the precursor protein has been eliminated. Overall, outcomes of solid organ transplantation are improving, but more data are needed to refine the selection criteria and the timing for organ transplantation, which should be performed in highly experienced centers involving multidisciplinary teams with close patient follow-up to detect amyloid recurrence.

Exceptional Liver Transplant Indications: Unveiling the Uncommon Landscape

“…The role of liver transplant in amyloidosis is controversial. Some data in the literature suggest that liver transplantation might be useful in patients with dominant hepatic involvement as they are not suitable for chemoimmunotherapy [46]. The first documented liver transplant for transthyretin amyloidosis was performed in 1990 with the purpose of removing the organ that had been producing this abnormal protein.…”

Expert recommendation from the Swiss Amyloidosis Network (SAN) for systemic AL-amyloidosis

“…Even among patients achieving haematological response, there is a significant proportion in whom organ damage is irreversible at the time of diagnosis or will continue to deteriorate owing to residual production of toxic immunoglobulins [91], sometimes even undetected by standard methods. For years, the role of solid organ transplant as an option in end-stage organ failure for patients with AL-amyloidosis was questioned, mainly because of the lack of effective plasma cell-directed therapy, complications with the allograft and organ donor shortage [92]. With the introduction of highly effective therapies and improvement in the management of transplant-related complications and supportive care, the perception changed.…”

Amyposomes, a nanotechnological chaperone with anti-amyloidogenic activity

“…chemotherapy for light chain amyloidosis, anti-inflammatory therapy in serum A amyloidosis, tetramer stabilising drugs, such as tafamidis, and antisense RNA therapy in transthyretin amyloidosis) and others are emerging from research. Unfortunately, in a significant proportion of patients, organ damage is irreversible at the time of diagnosis and solid organ transplantation is often the last option [ 6 , 7 ].…”