Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York.
Division of Nephrology, Department of Medicine, Columbia University Irving Medical Center, New York, New York.
J Am Soc Nephrol. 2020 Sep;31(9):1959-1968. doi: 10.1681/ASN.2020060802. Epub 2020 Jul 17.
Coronavirus disease 2019 (COVID-19) is thought to cause kidney injury by a variety of mechanisms. To date, pathologic analyses have been limited to patient reports and autopsy series.
We evaluated biopsy samples of native and allograft kidneys from patients with COVID-19 at a single center in New York City between March and June of 2020. We also used immunohistochemistry, hybridization, and electron microscopy to examine this tissue for presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The study group included 17 patients with COVID-19 (12 men, 12 black; median age of 54 years). Sixteen patients had comorbidities, including hypertension, obesity, diabetes, malignancy, or a kidney or heart allograft. Nine patients developed COVID-19 pneumonia. Fifteen patients (88%) presented with AKI; nine had nephrotic-range proteinuria. Among 14 patients with a native kidney biopsy, 5 were diagnosed with collapsing glomerulopathy, 1 was diagnosed with minimal change disease, 2 were diagnosed with membranous glomerulopathy, 1 was diagnosed with crescentic transformation of lupus nephritis, 1 was diagnosed with anti-GBM nephritis, and 4 were diagnosed with isolated acute tubular injury. The three allograft specimens showed grade 2A acute T cell-mediated rejection, cortical infarction, or acute tubular injury. Genotyping of three patients with collapsing glomerulopathy and the patient with minimal change disease revealed that all four patients had high-risk gene variants. We found no definitive evidence of SARS-CoV-2 in kidney cells. Biopsy diagnosis informed treatment and prognosis in all patients.
Patients with COVID-19 develop a wide spectrum of glomerular and tubular diseases. Our findings provide evidence against direct viral infection of the kidneys as the major pathomechanism for COVID-19-related kidney injury and implicate cytokine-mediated effects and heightened adaptive immune responses.
据认为，2019 年冠状病毒病（COVID-19）通过多种机制引起肾损伤。迄今为止，病理分析仅限于患者报告和尸检系列。
我们在 2020 年 3 月至 6 月期间在纽约市的一家单一中心评估了 COVID-19 患者的原生和同种异体肾活检样本。我们还使用免疫组织化学、杂交和电子显微镜检查了该组织中是否存在严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）。
研究组包括 17 名 COVID-19 患者（12 名男性，12 名黑人；中位年龄 54 岁）。16 名患者有合并症，包括高血压、肥胖、糖尿病、恶性肿瘤或肾脏或心脏同种异体移植物。9 名患者发生 COVID-19 肺炎。15 名患者（88%）出现 AKI；9 名患者出现肾病范围蛋白尿。在 14 名接受原生肾活检的患者中，5 例诊断为塌陷性肾小球病，1 例诊断为微小病变性肾病，2 例诊断为膜性肾小球病，1 例诊断为狼疮性肾炎新月体转化，1 例诊断为抗肾小球基底膜肾炎，4 例诊断为孤立性急性肾小管损伤。3 个同种异体移植物标本显示 2A 级急性 T 细胞介导的排斥反应、皮质梗死或急性肾小管损伤。对 4 例塌陷性肾小球病和 1 例微小病变性肾病患者进行基因分型发现，所有 4 例患者均存在高危基因变异。我们没有发现肾脏细胞中存在 SARS-CoV-2 的明确证据。在所有患者中，活检诊断均为治疗和预后提供了依据。
COVID-19 患者会出现广泛的肾小球和肾小管疾病。我们的发现提供了证据，证明 COVID-19 相关肾损伤的主要发病机制不是病毒直接感染肾脏，而是细胞因子介导的效应和适应性免疫反应增强。
