Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
J Am Soc Nephrol. 2021 Jan;32(1):33-40. doi: 10.1681/ASN.2020060804. Epub 2020 Nov 19.
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.
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 from one transplanted kidney and five native kidneys. Three of the six patients underwent genetic analysis of , the gene encoding the APOL1 protein, from DNA extracted from peripheral blood. In addition, we purified genomic DNA from paraffin-embedded tissue and performed genotype analysis of one of the native biopsies and the donor kidney graft.
All six patients were of recent African ancestry. They developed COVID-19-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 genotypes. One high-risk patient developed collapsing glomerulopathy in the engrafted kidney, which was transplanted from a donor who carried a low-risk 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.
Glomerular disease presenting as proteinuria with or without AKI is an important presentation of COVID-19 infection and may be associated with a high-risk genotype.
有研究记录了严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染患者出现高级蛋白尿相关的急性肾损伤（AKI）。在一些患者中，活检显示出塌陷性肾小球病，这是一种独特的肾小球损伤形式，与包括 HIV 在内的其他病毒有关。之前的患者报告描述了一些具有非洲血统的患者，他们在疾病早期就出现了肾病范围的蛋白尿和 AKI。
在这个患者系列中，我们鉴定了 6 例患有 2019 年冠状病毒病（COVID-19）、AKI 和肾病范围蛋白尿的患者。COVID-19 通过 SARS-CoV-2 感染的鼻咽拭子 RT-PCR 阳性来诊断。我们检查了 1 例移植肾和 5 例原肾的活检标本。6 例患者中的 3 例进行了基因分析，分析对象是编码 APOL1 蛋白的 基因，从外周血中提取的 DNA 进行分析。此外，我们从石蜡包埋组织中纯化基因组 DNA，并对 1 例原肾活检标本和供体肾移植物进行了 基因型分析。
所有 6 例患者均为近期非洲血统。他们发生了 COVID-19 相关 AKI，伴有足细胞病、塌陷性肾小球病或两者兼有。患者表现出一般较轻的呼吸道症状，无患者需要呼吸机支持。对 3 例患者进行的基因检测证实了高危 基因型。1 例携带高危 基因型的患者在移植肾中发生了塌陷性肾小球病，该移植肾的供者携带低危 基因型；这与目前的 APOL1 介导的肾损伤模型相矛盾，提示内在的肾表达 APOL1 可能不是肾毒性的驱动因素，特别是不是足细胞损伤的驱动因素。
以蛋白尿伴或不伴 AKI 为特征的肾小球疾病是 COVID-19 感染的一个重要表现，可能与高危 基因型有关。
