全切片扫描在肾组织轻链型淀粉样物质沉积患者研究中的应用

Clinicopathologic features and outcomes of light-chain amyloidosis(AL) patients based on digital whole slide imaging

目的:探讨轻链型淀粉样变性(AL型)淀粉样物质在肾组织沉积部位及程度与临床表现及预后的关系。方法:回顾分析经肾活检确诊的AL型淀粉样变性患者的临床病理资料,利用全切片扫描技术计算淀粉样物质占组织的百分比,分析其与临床及预后的关系。结果:AL型淀粉样变性患者259例,男性147例,中位年龄57岁,肾脏均受累,肠道受累71.06%,心脏受累43.22%。中位病程7月,蛋白尿4.80±3.15g/24h,19.31%的患者肾功能不全。中位随访时间22.3月,患者平均生存时间24.24月,1、2、3和5年人生存率分别为81.8%、64.1%、52.4%和29.6%;肾脏生存率分别为90.8%、82.3%、76.8%和47.8%。淀粉样物质累及肾小球(99.61%),肾血管(92.66%)和肾间质(50.19%)。淀粉样物质占肾小球、肾血管、肾间质及整个肾组织的百分比分别为11.81%±11.38%、14.14%±14.05%、3.34%±5.36%和4.25%±5.77%,且与多项临床指标具有相关性。淀粉样物质占肾小球百分比、年龄、尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)及尿视黄醇结合蛋白(RBP)为患者预后的独立危险因素。淀粉样物质占肾血管、肾间质及整个肾组织百分比,血清肌酐,尿RBP为肾脏预后的独立危险因素。结论:全切片扫描定量分析是观察淀粉样物质在肾脏不同部位沉积及其程度的有效方法,并证实蛋白尿、血清肌酐等与淀粉样物质肾脏不同部位沉积有一定相关性。肾脏不同部位淀粉样物质沉积与患者预后和肾脏预后相关。

Objective： To explore the location and severity of amyloid deposition on kidney and compare them with clinical features in patients with light-chain amyloidosis （AL）. Methodology ：The clinicopathological data of 259 patients with kidney biopsy-proven AL amyloidsis were retrospectively analyzed. The presence of amyloid was identified by positive congo red staining from digital whole slide imaging. Areas with amyloid deposition and glomerular, vascular and total tissue area were measured by digital WSI. Areas of amyloid deposition per total glomerular, vascular, interstitial and total tissue were calculated respectively using Aperio software. Results：They were 147 males and 102 females, with a median age of 57 years old. The patients frequently presented with edema and fatigue. The most common involved organ was kidney （ 100%）, followed by gastrointestinal tract （71.1% ） and heart （43.2%）. The median disease duration was 7 months. The mean level of proteinuria was 4. 80~ 3.15 g/24h. 50 patients had renal insufficiency. The median time of follow-up was 22. 3 months, and the mean patient survival time was 24. 2 months. The 1, 2, 3 and 5-year cumulative patient survival rates were 81.8%, 64. 1%, 52.4% and 29.6%, and cumulative renal survival rates were 90. 8%, 82. 3%, 76. 8% and 47.8%. The numbers of patients who had amyloid deposition in glomerular, vascular and interstitial areas were 258 （99. 6%）, 239 （92. 7%） and 165 （50. 2%） respectively. The rates of glomerular, vascular, interstitial and total tissue areas amyloid deposits were 11.8 ± 11.4%, 14. 1 ± 14. 1%, 3.34 ± 5.36% and 4. 25 ± 5.77% respectively, which were associated with several clinical parameters. The rate of glomerular amyloid deposits, age, urinary N-acetyl-B-D- glucosaminidase to creatinine ratios （NAG） and retinol-binding protein （RBP） were important risk factors of patient survival. The rates of vascular, interstitial, total tissue areas amyloid deposits, serum creatinine （SCr） and RBP were important risk factors of renal survival. Conclusion：The digital whole slide imaging is convenient, practical and feasible in evaluation of amyloid deposits. The rates of glomerular and vascular amyloid deposit were same and higher than that in interstitial areas. Proteinuria and SCr were associated with amyloid deposition. The amyloid deposition was related with patient survival and renal survival.