Type VI collagen-related nephropathy.
Type VI collagen-related nephropathy.
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DOI：
10.1093/ckj/sfac126
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发表时间：
2023-01
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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作者：
一位84岁男性，有4年的微量血尿和蛋白尿病史，因高血压和肾范围蛋白尿加重而转诊至我院。11年前患左侧青光眼，2年前患脑腔隙性梗死。他的药物包括氯吡格雷（75毫克/天）预防中风；氨氯地平（5mg /天）、依那普利（5mg /天）和阿唑塞米（30mg /天）用于高血压；阿托伐他汀（5mg /天）治疗高脂血症；naftopidil （50 mg/天）用于治疗良性前列腺肥大。他还被诊断出患有前列腺癌，但在常规门诊就诊中没有任何进展。他被送进我们医院作进一步评估。他的血压是189/95毫米汞柱。双侧小腿凹陷性水肿，未见紫癜。尿检显示微量血尿和蛋白尿（尿蛋白：肌酐比值为5.67 g/g Cr；补充数据，表S1）。他基于胱抑素c估计肾小球滤过率（eGFR）为53.4 mL/min/1.73 m2。血清白蛋白水平降低，血清总胆固醇水平升高。抗核抗体、低温球蛋白、低温纤维蛋白原均为阴性，补体水平正常。血清和尿液免疫电泳结果均为阴性。胸部CT示双侧胸腔积液及心包积液，腹部CT示双肾单纯性囊肿，无萎缩。肾活检显示肾小球分叶状，肾小球基底膜增厚和重复，系膜细胞增多和轻度毛细血管内细胞增多（补充数据，图S1）。免疫荧光研究显示免疫球蛋白M （IgM）和补体3 （C3）颗粒沉积沿肾小球毛细血管壁和系膜区（补充数据，图S2）。κ有轻链限制。在偏光显微镜下，直接快速猩红染色为阴性。透射电镜下在上皮下、膜内和内皮下区域观察到电子致密沉积物（图1a）。高倍观察显示，沉积物的纤维结构宽度为8-14 nm，与阶梯形成有关，周期性为25-30 nm（图1b）。采用激光显微解剖-液相色谱-串联质谱法对石蜡切片肾小球进行分析。结果发现胶原α1 （VI）、α2 （VI）和α3 （VI）链增加；IgM;C3;κ轻链；纤维蛋白原α、β和γ链和载脂蛋白B-100（补充数据，图S3）。兔抗胶原α1 （VI）链多克隆抗体的免疫荧光研究显示毛细血管壁段呈阳性（补充数据，图S4）。静脉注射甲基强的松龙（500 mg/天）连续3天，因为阿齐沙坦没有改善蛋白尿，在7.5 mg/天的强的松龙治疗下，尿蛋白：肌酐比和血清白蛋白值分别为0.73 g/g Cr和3.2 g/dl。虽然本病例类似于低温纤维蛋白原相关的肾小球肾炎[2-4]，但在血浆中未发现低温纤维蛋白原。有两个类似的不寻常的、有组织的矿床[5,6]。然而，蛋白质组学分析是
An 84-year-old man with a 4-year history of microhematuria and proteinuria was referred to our hospital because of the exacerbation of hypertension and nephrotic-range proteinuria. He had developed left glaucoma 11 years previously and suffered a cerebral lacunar infarction 2 years previously. His medications included clopidogrel (75 mg/day) for stroke prevention; amlodipine (5 mg/day), enalapril (5 mg/day), and azosemide (30 mg/day) for hypertension; atorvastatin (5 mg/day) for hyperlipidemia; and naftopidil (50 mg/day) for benign prostatic hypertrophy. He had also been diagnosed with prostate cancer, which had not shown progression at regular outpatient visits. He was admitted to our hospital for further evaluation. His blood pressure was 189/95 mmHg. Pitting edema was found on his bilateral lower legs, without any purpura. A urinalysis revealed microhematuria and proteinuria (the urinary protein: creatinine ratio was 5.67 g/g Cr; Supplementary data, Table S1). His cystatin C–based estimated glomerular filtration rate (eGFR) was 53.4 mL/min/1.73 m2. His serum albumin level was decreased and his serum total cholesterol level was increased. Antinuclear antibody, cryoglobulin and cryofibrinogen were all negative with normal complement levels. Serum and urine immunoelectrophoresis showed negative results. Chest computed tomography (CT) showed bilateral pleural effusions and pericardial fluid and abdominal CT showed several simple cysts in both kidneys without atrophy.A kidney biopsy showed lobulated glomeruli with thickening and duplication of the glomerular basement membranes (GBMs), mesangial hypercellularity and mild endocapillary hypercellularity (Supplementary data, Figure S1). An immunofluorescence study revealed granular deposition of immunoglobulin M (IgM) and complement 3 (C3) along the glomerular capillary wall and in the mesangial area (Supplementary data, Figure S2). There was a light chain restriction for κ. Direct fast scarlet staining was negative under polarized light microscopy. Electron-dense deposits were observed in the subepithelial, intramembranous and subendothelial area under transmission electron microscopy (Figure 1 A). A high-magnification view of the deposits revealed fibrillary structures of 8–14 nm in width that were associated with ladder formation, with a periodicity of 25–30 nm (Figure 1 B). Glomeruli on paraffin sections were analyzed with laser-capture microdissection followed by liquid chromatography–tandem mass spectrometry. The results identified an increase in collagen α1 (VI), α2 (VI) and α3 (VI) chains; IgM; C3; κ light chain; fibrinogen α, β and γ chains and apolipoprotein B-100 (Supplementary data, Figure S3). An immunofluorescence study using rabbit polyclonal antibody against collagen α1 (VI) chain showed positive findings on capillary wall segments (Supplementary data, Figure S4). Intravenous methylprednisolone (500 mg/day) was administered for 3 consecutive days, as proteinuria did not improve with azilsartan and the urinary protein: creatinine ratio and serum albumin value were 0.73 g/g Cr and 3.2 g/dl, respectively, under treatment with prednisolone at a dose of 7.5 mg/day. While the present case resembled cryofibrinogen-associated glomerulonephritis [2–4], cryofibrinogen was not identified in the plasma. There have been two similar cases with unusual, organized deposits [5, 6]. However, a proteomic analysis was
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影响因子：
6.1
作者：
Ohtani, Hiroshi;Wakui, Hideki;Sawada, Ken-ichi
通讯作者：
Sawada, Ken-ichi
影响因子：
1
作者：
Kakeshita, Kota;Yamazaki, Hidenori;Kinugawa, Koichiro
通讯作者：
Kinugawa, Koichiro
影响因子：
1
作者：
Hara, Shigeo;Tsukaguchi, Hiroyasu;Joh, Kensuke
通讯作者：
Joh, Kensuke
影响因子：
4.6
作者：
Herrera, Guillermo A.;Turbat-Herrera, Elba A.
通讯作者：
Turbat-Herrera, Elba A.
影响因子：
2.3
作者：
Ibuki, Emi;Shiraishi, Aiko;Haba, Reiji
通讯作者：
Haba, Reiji