Transthyretin Amyloidosis and the Kidney

Abstract

SummaryThe amyloidoses are protein-misfolding disorders associated with progressive organ dysfunction. Immunoglobulin light chain is the most common, amyloid A the longest recognized, and transthyretin-associated amyloidosis (ATTR) the most frequent inherited systemic form. Although ATTR, an autosomal-dominant disease, is associated with at least 100 different transthyretin (TTR) mutations, the single amino-acid substitution of methionine for valine at position 30 is the most common mutation. Each variant has a different organ involvement, although clinical differences attributed to environmental and genetic factors exist within the same mutation. Peripheral neuropathy and cardiomyopathy are broadly described, and insights into disease reveal that kidney impairment and proteinuria are also clinical features. This review combines clinical and laboratory findings of renal involvement from the main geographic regions of disease occurrence and for different mutations of TTR. Fifteen nephropathic variants have been described, but the TTR V30M mutation is the best documented. Nephropathy affects patients with late-onset neuropathy, low penetrance in the family, and cardiac dysrhythmias. Microalbuminuria can be the disorder's first presentation, even before the onset of neuropathy. Amyloid renal deposits commonly occur, even in the absence of urinary abnormalities. The experience with renal replacement therapy is based on hemodialysis, which is associated with poor survival. Because TTR is synthesized mainly in the liver, liver transplantation has been considered an acceptable treatment; simultaneous liver-kidney transplantation is recommended to avoid recurrence of nephropathy. In addition, the kidney-safety profile of new drugs in development may soon be available.

Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis – Report from the Transthyretin Amyloidosis Outcome Survey (THAOS)

“…Finally, renal involvement of ATTR, although rare [30], might explain the worsening of renal function. In total, 15 mutations of the TTR gene have so far been associated with renal involvement; among these Val30Met is by far the best characterized variant [31]. …”

Transthyretin-Related Familial Amyloid Polyneuropathy: In the Light of New Developments

“…Urinary involvement often affects patients in late stages of the disease, but microalbuminuria may be the first finding of a manifest nephropathy. The occurrence of kidney failure is related with poor prognosis (9). Amyloid accumulation in the CNS includes leptomeningeal involvement and accumulation in the media and adventitia of small and medium-diameter arteries, and veins of the cerebral cortex.…”

Psychopathological Dimensions in Portuguese Subjects with Transthyretin Familial Amyloid Polyneuropathy

“…The clinical picture is dominated by a mixed sensory, motor, and autonomic neuropathy; severe nephrological, cardiac, ophthalmological, vesical, gastrointestinal, sexual, and central nervous system symptoms are related to systemic amyloid deposition [14,15,16,17,18]. …”