Diagnosis, Pathogenesis, Treatment, and Prognosis of Hereditary Fibrinogen Aα-Chain Amyloidosis
Diagnosis, Pathogenesis, Treatment, and Prognosis of Hereditary Fibrinogen Aα-Chain Amyloidosis
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DOI：
10.1681/asn.2008060614
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发表时间：
2009-02-01
影响因子：
13.6
通讯作者：
Hawkins, Philip N.
中科院分区：
文献类型：
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作者：
Gillmore, Julian D.;Lachmann, Helen J.;Hawkins, Philip N.
在英国，纤维蛋白原A α链基因突变是遗传性肾淀粉样变性的最常见原因。先前关于纤维蛋白原A α链淀粉样变性的报道是孤立的，通常是在一种新的淀粉样突变的背景下。在这里，我们描述了71例纤维蛋白原淀粉样变性，谁是前瞻性研究在英国国家淀粉样变性中心。中位年龄为58岁，肾脏受累导致所有病例的诊断。即使在中位随访4年后，临床上显著的肾外疾病也很少见。肾组织学特征：肾小球显著增大，淀粉样蛋白沉积几乎完全闭塞正常结构，很少或没有血管或间质淀粉样蛋白。我们在纤维蛋白原中发现了四个淀粉样蛋白突变（P552 H、E540 V、T538 K和T525 fs）。肾脏疾病的家族史往往是缺席。从发病到终末期肾病的中位时间为4.6年，估计的中位患者生存期为15.2年。44例终末期肾病患者中位生存期为9.3年。12例肾移植患者平均存活时间为6.0（0-12.2）年。移植后中位随访时间为5.8年，7例移植物失败，其中3例在5.8、6.0和7.4年后复发淀粉样蛋白; 3例移植物因手术原因立即失败，1例在5.8年后因移植肾小球病失败，无淀粉样蛋白的组织学证据。在删失时，移植物的最长存活时间为12.2年。总之，纤维蛋白原淀粉样变性是一种主要的肾脏疾病，其特征是可变的变性，独特的组织学表现，蛋白尿和进行性肾损害。生存率明显优于系统性AL淀粉样变性，肾脏替代治疗的结局与年龄匹配的非糖尿病肾病患者相当。
Mutations in the fibrinogen A alpha-chain gene are the most common cause of hereditary renal amyloidosis in the United Kingdom. Previous reports of fibrinogen A alpha-chain amyloidosis have been in isolated kindreds, usually in the context of a novel amyloidogenic mutation. Here, we describe 71 patients with fibrinogen amyloidosis, who were prospectively studied at the UK National Amyloidosis Centre. Median age at presentation was 58 yr, and renal involvement led to diagnosis in all cases. Even after a median follow-up of 4 yr, clinically significant extra-renal disease was rare. Renal histology was characteristic: striking glomerular enlargement with almost complete obliteration of the normal architecture by amyloid deposition and little or no vascular or interstitial amyloid. We discovered four amyloidogenic mutations in fibrinogen (P552H, E540V, T538K, and T525fs). A family history of renal disease was frequently absent. Median time from presentation to ESRD was 4.6 yr, and the estimated median patient survival from presentation was 15.2 yr. Among 44 patients who reached ESRD, median survival was 9.3 yr. Twelve renal transplants survived for a median of 6.0 (0-12.2) yr. Seven grafts had failed after median follow up from transplantation of 5.8 yr, including three from recurrent amyloid after 5.8, 6.0, and 7.4 yr; three grafts failed immediately for surgical reasons and one failed from transplant glomerulopathy after 5.8 yr with no histological evidence of amyloid. At censor, the longest surviving graft was 12.2 yr. In summary, fibrinogen amyloidosis is predominantly a renal disease characterized by variable penetrance, distinctive histological appearance, proteinuria, and progressive renal impairment. Survival is markedly better than observed with systemic AL amyloidosis, and outcomes with renal replacement therapy are comparable to those for age-matched individuals with nondi abetic renal disease.