Department of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Nephrology, Université Paris Descartes, Paris.
Department of Nephrology, Hôpital Jean Bernard, Valenciennes, France.
Am J Kidney Dis. 2020 Sep;76(3):384-391. doi: 10.1053/j.ajkd.2020.02.445. Epub 2020 Jul 10.
RATIONALE & OBJECTIVE: Fibrinogen A α-chain amyloidosis (AFib amyloidosis) is a form of amyloidosis resulting from mutations in the fibrinogen A α-chain gene (FGA), causing progressive kidney disease leading to kidney failure. Treatment may include kidney transplantation (KT) or liver-kidney transplantation (LKT), but it is not clear what factors should guide this decision. The aim of this study was to characterize the natural history and long-term outcomes of this disease, with and without organ transplantation, among patients with AFib amyloidosis and various FGA variants.
Case series.
SETTING & PARTICIPANTS: 32 patients with AFib amyloidosis diagnosed by genetic testing in France between 1983 and 2014, with a median follow-up of 93 (range, 4-192) months, were included.
Median age at diagnosis was 51.5 (range, 12-77) years. Clinical presentation consisted of proteinuria (93%), hypertension (83%), and kidney failure (68%). Manifestations of kidney disease appeared on average at age 57 (range, 36-77) years in patients with the E526V variant, at age 45 (range, 12-59) years in those with the R554L variant (P<0.001), and at age 24.5 (range, 12-31) years in those with frameshift variants (P<0.001). KT was performed in 15 patients and LKT was performed in 4. In KT patients with the E526V variant, recurrence of AFib amyloidosis in the kidney graft was less common than with a non-E526V (R554L or frameshift) variant (22% vs 83%; P=0.03) and led to graft loss less frequently (33% vs 100%). Amyloid recurrence was not observed in patients after LKT.
Analyses were based on clinically available historical data. Small number of patients with non-E526V and frameshift variants.
Our study suggests phenotypic variability in the natural history of AFib amyloidosis, depending on the FGA mutation type. KT appears to be a viable option for patients with the most common E526V variant, whereas LKT may be a preferred option for patients with frameshift variants.
纤维蛋白原 Aα 链淀粉样变性（AFib 淀粉样变性）是一种由纤维蛋白原 Aα 链基因（FGA）突变引起的淀粉样变性，可导致进行性肾病，最终导致肾衰竭。治疗方法可能包括肾移植（KT）或肝肾联合移植（LKT），但目前尚不清楚应根据哪些因素来决定这一治疗方案。本研究的目的是描述在法国于 1983 年至 2014 年间通过基因检测诊断为 AFib 淀粉样变性的患者中，不同纤维蛋白原 Aα 链基因（FGA）变异型患者在接受或未接受器官移植时的自然病史和长期预后。
病例系列研究。
共纳入 32 例在法国通过基因检测诊断为 AFib 淀粉样变性的患者，中位随访时间为 93（范围，4-192）个月。
诊断时的中位年龄为 51.5（范围，12-77）岁。临床表现为蛋白尿（93%）、高血压（83%）和肾衰竭（68%）。在 E526V 变异型患者中，肾脏疾病的表现平均在 57 岁（范围，36-77）出现，在 R554L 变异型患者中平均在 45 岁（范围，12-59）出现，在移码变异型患者中平均在 24.5 岁（范围，12-31）出现（P＜0.001）。15 例患者接受了 KT，4 例患者接受了 LKT。在接受 KT 的 E526V 变异型患者中，与非 E526V（R554L 或移码）变异型患者相比，纤维蛋白原 Aα 链淀粉样变性在移植肾中的复发较少见（22%比 83%；P=0.03），且较少导致移植物丢失（33%比 100%）。LKT 后未观察到淀粉样蛋白复发。
分析基于临床可获得的历史数据。非 E526V 和移码变异型患者数量较少。
本研究表明，纤维蛋白原 Aα 链淀粉样变性的自然病史存在表型异质性，这取决于 FGA 突变类型。对于最常见的 E526V 变异型患者，KT 似乎是一种可行的选择，而对于移码变异型患者，LKT 可能是一种首选的选择。
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