RATIONALE & OBJECTIVE Amyloidosis derived from apolipoprotein C-II (AApoCII) is a recently discovered, rare form of amyloidosis. Data on clinical presentations and natural history are very limited. This study defines the clinicopathologic, proteomic and outcome characteristics of renal AApoCII. STUDY DESIGN Case series. SETTING & PARTICIPANTS Twenty-five renal AApoCII cases were identified from the Mayo Clinic Tissue Proteomics Laboratory archives from January 2008 through January 2024. FINDINGS All patients were White, 19 were ≥65 years old at diagnosis, and 18 were female. Seven had a family history of CKD. Patients presented with proteinuria (median 3.3 g/day) and reduced kidney function (n=16, median creatinine 1.6 mg/dl). No patient had clinical evidence of other organ involvement by amyloidosis or features of monogenic hypertriglyceridemia. Histologically, amyloid deposits were often weakly positive for Congo red and involved glomeruli in all cases (with a nodular pattern in 22), whereas extraglomerular involvement was less common and generally mild. Proteomic analysis revealed abundant spectra for Apo C-II and for all 3 amyloid signature proteins (Apo E, Apo A-IV and SAP) in all cases, and detected an Apo C-II variant in 14 (K19T [p.Lys41Thr] in 12 and E47V [p.Glu69Val] in 2). Among 22 patients with follow-up available, there were 12 ESKD events and 2 deaths without ESKD during an average (SE) follow up of 75.5 (12.5) months. LIMITATIONS Retrospective design, small sample size, APOC2 gene sequencing performed in a smaller subset. CONCLUSIONS AApoCII mostly affects the kidney, and manifests in the elderly with proteinuria and CKD. A minority of these patients had a family history of kidney disease. Kidney failure occurred in about half, whereas overall survival was more favorable.

中文翻译：

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肾载脂蛋白 C-II 淀粉样变性的临床病理学、蛋白质组学和结果特征：病例系列。


基本原理和目标 淀粉样变性源自载脂蛋白C-II（AApoCII）是一种最近发现的罕见形式的淀粉样变性。关于临床表现和自然病程的数据非常有限。本研究定义了肾脏 AApoCII 的临床病理学、蛋白质组学和结果特征。研究设计 案例系列。地点和参与者 从2008年1月至2024年1月的梅奥诊所组织蛋白质组学实验室档案中发现了25例肾脏AApoCII病例。结果 所有患者均为白人，19 例诊断时年龄为 ≥65 岁，18 例为女性。7 例有 CKD 家族史。患者表现为蛋白尿 （中位 3.3 g/d） 和肾功能下降 （n=16，中位肌酐 1.6 mg/dl）。没有患者有淀粉样变性累及其他器官的临床证据或单基因高甘油三酯血症的特征。组织学上，刚果红淀粉样蛋白沉积通常呈弱阳性，并且在所有病例中都累及肾小球（22 例为结节型），而肾小球外受累较少见且通常较轻。蛋白质组学分析显示，在所有病例中，Apo C-II 和所有 3 种淀粉样蛋白特征蛋白 （Apo E、Apo A-IV 和 SAP） 都有丰富的光谱，并在 14 例中检测到 Apo C-II 变体（12 例中 K19T [p.Lys41Thr]，2 例中检测到 E47V [p.Glu69Val]）。在 22 例可随访的患者中，在平均 75.5 （SE） 的随访 75.5 （12.5） 个月期间，有 12 例 ESKD 事件和 2 例无 ESKD 死亡。局限性 回顾性设计，小样本量，在较小的子集中进行 APOC2 基因测序。结论 AApoCII 主要累及肾脏，多见于蛋白尿和 CKD 的老年人。这些患者中有少数有肾病家族史。 肾衰竭发生率约为一半，而总生存期更有利。