COVID-19-Associated Glomerular Disease
COVID-19-Associated Glomerular Disease
复制标题
DOI：
10.1681/asn.2020060804
复制
发表时间：
2021-01-01
影响因子：
13.6
通讯作者：
Quaggin, Susan E.
中科院分区：
文献类型：
--
作者：
Shetty, Aneesha A.;Tawhari, Ibrahim;Quaggin, Susan E.
背景研究已证实严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染患者的阿基伴高级别蛋白尿。在一些患者中，活检发现了塌陷性肾小球病，这是一种与其他病毒（包括HIV）相关的独特形式的肾小球损伤。先前的患者报告描述了非洲血统的患者在病程早期发生肾病范围蛋白尿和阿基。方法在该患者系列中，我们确定了6例2019年冠状病毒病（COVID-19）、阿基和肾病范围蛋白尿患者。通过SARS-CoV-2感染的鼻咽拭子RT-PCR阳性诊断COVID-19。我们检查了一个移植肾和五个自体肾的活检标本。六名患者中的三名接受了APOL 1基因分析，APOL 1基因编码APOL 1蛋白，从外周血提取的DNA。此外，我们纯化基因组DNA石蜡包埋组织和APOL 1基因型分析的本地活检和供体肾graft.Results所有6例患者最近的非洲血统。他们发生了COVID 19相关的阿基，伴足细胞病、塌陷性肾小球病或两者兼而有之。患者一般表现出轻微的呼吸道症状，没有患者需要呼吸机支持。在三名患者中进行的基因检测证实了高风险APOL 1基因型。一名APOL 1高风险患者在移植肾中发生了塌陷性肾小球病，该肾移植自携带低风险APOL 1基因型的供体;这与目前APOL 1介导的肾损伤模型相矛盾，并提示APOL 1的内在肾表达可能不是肾毒性的驱动因素，结论肾小球疾病表现为蛋白尿伴或不伴阿基是COVID-19感染的重要表现，可能与高危APOL 1基因型相关。
Background Studies have documented AKI with high-grade proteinuria in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In some patients, biopsies have revealed collapsing glomerulopathy, a distinct form of glomerular injury that has been associated with other viruses, including HIV. Previous patient reports have described patients of African ancestry who developed nephrotic-range proteinuria and AKI early in the course of disease.Methods In this patient series, we identified six patients with coronavirus disease 2019 (COVID-19), AKI, and nephrotic-range proteinuria. COVID-19 was diagnosed by a positive nasopharyngeal swab RT-PCR for SARS-CoV-2 infection. We examined biopsy specimens fromone transplanted kidney and five native kidneys. Three of the six patients underwent genetic analysis of APOL1, the gene encoding the APOL1 protein, from DNA extracted from peripheral blood. In addition, we purified genomic DNA from paraffin-embedded tissue and performed APOL1 genotype analysis of one of the native biopsies and the donor kidney graft.Results All six patients were of recent African ancestry. They developed COVID19-associated AKI with podocytopathy, collapsing glomerulopathy, or both. Patients exhibited generally mild respiratory symptoms, and no patient required ventilator support. Genetic testing performed in three patients confirmed high-risk APOL1 genotypes. One APOL1 high- risk patient developed collapsing glomerulopathy in the engrafted kidney, which was transplanted from a donor who carried a low-risk APOL1 genotype; this contradicts current models of APOL1-mediated kidney injury, and suggests that intrinsic renal expression of APOL1 may not be the driver of nephrotoxicity and specifically, of podocyte injury.Conclusions Glomerular disease presenting as proteinuria with or without AKI is an important presentation of COVID-19 infection and may be associated with a highrisk APOL1 genotype.