061
OUTCOME OF RENAL TRANSPLANTATION
NEUROPATHIC SYSTEMIC AMYLOIDOSIS
IN
HEREDITARY
NON-
Sattianayagam, P,T*, Gibbs S,D,J, Rowcenzio D, Lachmann H,J, Hawkins P,N,
Gillmore, J,D
Royal Free and University College Medical School, London
BACKGROUND: Hereditary non-neuropathic systemic amyloidosis forms a group of
conditions that are inherited in an autosomal dominant manner and frequently present with
proteinuric renal dysfunction, which typically progresses to end-stage renal failure (ESRF). The
amyloidogenic variant precursor proteins, encoded by mutations in the respective genes, are
derived from extra-renal tissues such as the liver (fibrinogen A-alpha chain, apolipoprotein AI
and lysozyme) and the gastrointestinal tract (apolipoprotein AI and lysozyme). Renal
transplantation (RTx) has a role by replacing the failing kidneys but with ongoing production of
the respective amyloidogenic variant protein, there is a theoretical risk of graft failure secondary
to recurrent amyloid.
METHODS: All patients with renal amyloidosis secondary to variant fibrinogen A-alpha
(AFib), variant apolipoprotein AI (AApo AI) and variant lysozyme (ALys) who had RTx were
prospectively followed up at the UK National Amyloidosis Centre (NAC) between 1979 and
2009. We evaluated clinical features and RTx outcomes.
Results: Ten patients with AFib (all with Glu526Val mutations), 10 with AApo AI (5 with
Gly26Arg mutations, 2 with del 70-72 and 1 each with Trp50Arg, Leu60Arg and Leu64Pro
mutations) and 1 with ALys (Asp67His mutation) were identified, who had undergone isolated
RTx. AFib, AApo AI and ALys patients were followed from diagnosis of amyloidosis for a
median (range) of 10.2 (4.4-18), 12.8 (2.1-31), and 27.6 years respectively. A renal presentation
was universal. No patient had an amyloid-related cardiomyopathy or autonomic neuropathy.
One patient with AApo AI had an amyloid-related peripheral neuropathy. The median (range)
age at presentation was 55 (36-64), 38 (18-56) and 22 years for AFib, AApo AI and ALys
respectively. Median (range) time to ESRF from presentation was 23 (1-100), 60 (8-156) and
252 months respectively. In the AFib group RTx was undertaken twice in 2 patients. Median
(range) renal allograft survival by Kaplan-Meier analysis in this group was 6.7 years (0–12); 7
grafts were lost, 3 due to recurrent amyloid after 5.8, 6 and 7.4 years, 3 were lost in the
immediate post-operative period and 1 due to transplant glomerulopathy after 5.8 years. In the
AApo AI group, RTx was undertaken twice in 1 patient. Median (range) renal allograft survival
by Kaplan-Meier analysis in this group was 25 years (0.3-26.2). Three grafts failed, 2 due to
amyloid recurrence 6 and 25 years after RTx and 1 due to chronic rejection after 8.6 years. The
patient with ALys has good graft function 5 years after RTx with no evidence of amyloid
recurrence.
CONCLUSIONS: RTx is a viable option in patients with hereditary non-neuropathic systemic
amyloidosis with dominant renal disease. The progression to ESRF appears to be quicker in
patients with AFib than in those with AApo AI. Graft survival is excellent irrespective of the
amyloid fibril type, but appears to be substantially better in AApo AI than in AFib, consistent
with the slower natural history of the disease generally. The fact that there is ongoing
production of the variant amyloid precursor protein from extra-renal sources should not deter
from consideration of RTx in patients with hereditary renal amyloidosis.