End-stage renal disease in familial amyloidosis ATTR Val30Met: a definitive indication to combined liver-kidney transplantation.

AUTOSOMAL dominant amyloidoses characterized so far are most commonly associated with transthyretin (TTR), a plasma protein synthesized by the liver. The single gene for TTR is located on human chromosome 18; more than 70 TTR mutations have been documented. The most common type of hereditary amyloidosis is familial amyloid polyneuropathy type I (FAP, Portuguese type), a neuropathic form associated with a substitution of methionine for valine at position 30 of the TTR gene, TTR Val30Met. The largest number of patients and families with this mutation has been identified in Portugal, but now it has been recognized worldwide. FAP in Portugal usually begins in the third or fourth decade of life with death occuring about 11 years later. The clinical disease usually starts as a sensory neuropathy in the lower extremities, but autonomic and gastrointestinal features may occur early. Motor neuropathy usually manifests itself later with cardiac conduction disturbances frequently leading to the need for artificial pacing. Vitreous deposits of amyloid have been reported, most particularly in Swedish families. Cachexia has been described as a significant factor in mortality. Orthotopic liver transplantation (OLT) is widely recommended for patients affected by FAP; it is recognized as the only specific treatment for this disease. Virtually all TTR is produced by the liver, and, therefore, OLT halts the supply of variant amyloidogenic TTR (ATTR). Amyloid proteins have different organ specificity, leading to variations in clinical features. Classically, nephropathic and nonneuropathic autosomal dominant amyloidoses are associated with apolipoprotein A-I and A-II, fibrinogen A -chain, and lysozyme. Renal amyloidosis also has been described in FAP. In Portugal, approximately one third of FAP patients have clinical renal features with varying degrees of proteinuria and renal failure. The progression to end-stage renal disease (ESRD) occurs in 10% of Portuguese patients, more than 10 years after the onset of symptoms (Lobato et al, unpublished data). Although dialysis may prolong life, it does not prevent the progression of systemic amyloid involvement; death occurred, on average, at 22 months after renal replacement therapy. The cause was infection in one half of the patients (Lobato et al, unpublished data). The first successful renal transplantation in a patient with renal amyloidosis was reported in 1968, but until now this treatment has been associated with poor graft and patient survival. Most published series concerning renal transplantation in amyloidosis deal with familial Mediterranean fever or other forms of reactive amyloidosis (AA type). The results of kidney transplantation in ATTR have not been described. In patients with FAP undergoing dialysis, the potential advantages of simultaneous liver-kidney transplantation instead of isolated kidney transplantation are to avoid the progression of systemic manifestations and the recurrence of renal amyloidosis. The obstacles to renal transplantation