Progressive Wild-Type Transthyretin Deposition after Liver Transplantation Preferentially Occurs onto Myocardium in FAP Patients

Yazaki, Masahide; Mitsuhashi, Shigeaki; Tokuda, Takahiko; Kametani, Fuyuki; Takei, Yo‐ichi; Koyama, Jun; Kawamorita, A.; Kanno, Hiroyuki; Ikeda, Shu Ichi

doi:10.1111/j.1600-6143.2006.01585.x

Cited by 107 publications

(73 citation statements)

References 24 publications

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“…Scintigraphy with 123 I serum amyloid P component showed mobilization of visceral amyloid, namely in the kidney, although mobilization of renal deposits by histology has never been proven (54). Support for de novo amyloid deposition was demonstrated by the type of fibrils extracted from the kidney before OLT (55). The fibrils did not contain obvious WT-TTR; however, after OLT, WT-TTR was evident, in a process similar to that in the heart, although in a less substantial amount.…”

Section: Treatment Of Attrmentioning

confidence: 99%

Transthyretin Amyloidosis and the Kidney

Lobato

Rocha

2012

Clinical Journal of the American Society of Nephrology

121

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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.

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Section: Treatment Of Attrmentioning

confidence: 99%

Transthyretin Amyloidosis and the Kidney

Lobato

Rocha

2012

Clinical Journal of the American Society of Nephrology

121

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“…The amount of amyloid deposition in nerve tissues including the entire length of the peripheral nerves, dorsal root and sympathetic ganglia is greater in early-onset patients [40], while in late-onset patients the accumulation of Congo-red-negative but TTR-immunoreactive non-fibrillar protein is abundant in these tissues [17]. This pathologic amyloid-related protein deposition consists of both variant and wild type TTR [41], the latter being predominant in the involved tissues in late-onset patients [17]. These findings indicate that the underlying pathogenetic mechanism of amyloid neuropathy differs between Kodaira et al 17 of 26 both types.…”

Section: Difference In Pathophysiology Between Endemic-versus Non-endmentioning

confidence: 99%

Electrophysiological features of familial amyloid polyneuropathy in endemic area

Kodaira

Morita

Shimojima

et al. 2011

Amyloid

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The process of deterioration of peripheral nerve function in familial amyloid polyneuropathy (FAP) with amyloidogenic transthyretin (ATTR) Val30Met has not been systematically evaluated hitherto. We performed nerve conduction studies in 69 patients with FAP with ATTR Val30Met from one of the endemic areas in Japan. Sensory conduction velocity (SCV), motor conduction velocity (MCV), the size of the compound muscle action potential (CMAP), and distal latency (DL) were measured in the ulnar and tibial nerves. SCV was evaluated using the orthodromic method with needle recording electrodes. These electrophysiological parameters were compared with clinical stage of FAP and duration of neuropathy. When subjects noted minimal neuropathic symptoms only in the feet, motor and sensory nerve function in both the hands and feet had already been disturbed. Sensory nerve action potential on the foot disappeared more rapidly than CMAP. CMAP on foot muscle rapidly decreased during the initial 2 years and completely disappeared within 10 years. The duration of illness and deterioration parameters (CMAP of the abductor minimi muscle, MCV and SCV of the ulnar nerve, and DL of both ulnar and tibial nerves) were linearly correlated. CMAP was the most sensitive and reliable parameter to evaluate motor nerve degeneration in FAP.

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“…Since the source of variant TTR production leading to amyloid fibril is removed at the time of OLT, the accumulation of new amyloid deposits is completely unexpected. Subsequent evaluation of the amyloid deposits has shown that wild-type TTR is present in increased amounts in the heart following OLT [62,63]. Thus, it appears that wild-type TTR can continue to form amyloid deposits, particularly in the heart, in patients with ATTR following OLT.…”

Section: Treatment Of Attrmentioning

confidence: 99%