AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL1 High-Risk Genotype
AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL1 High-Risk Genotype
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DOI：
10.1681/asn.2020050558
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发表时间：
2020-08-01
影响因子：
13.6
通讯作者：
Velez, Juan Carlos Q.
中科院分区：
文献类型：
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作者：
Wu, Huijuan;Larsen, Christopher P.;Velez, Juan Carlos Q.
背景 肾脏受累是 COVID-19 的一个特征，黑人患者的病情可能很严重。先前的研究将塌陷性肾小球病（包括 HIV 相关肾病患者）的易感性增加与在非洲人后裔中更常见的载脂蛋白 L1 (APOL1) 变异联系起来。方法为了调查六名患有 AKI 和新发肾病范围蛋白尿的 COVID-19 黑人患者的遗传、组织病理学和分子特征，我们获取了肾组织活检组织，通过原位杂交进行病毒检测，并通过 NanoString 进行检测。 COVID-19 和急性肾小管损伤相关基因。我们还收集了外周血用于 APOL1 基因分型。 结果 该病例系列包括 6 名患有 COVID-19 的黑人患者（四名男性，两名女性），平均年龄 55 岁。活检当天，平均血清肌酐为 6.5 mg/dl，平均尿蛋白-肌酐比为 11.5 g。肾活检标本显示塌陷性肾小球病、广泛的足突消失和局灶性/弥漫性急性肾小管损伤。三名患者有内皮网状聚集。我们没有发现病毒颗粒或 SARS-CoV-2 RNA 的证据。与对照相比，NanoString 显示趋化因子基因表达升高，以及与急性肾小管损伤相关的基因表达变化。所有六名患者均具有 APOL1 高风险基因型。五名患者需要透析（其中两人死亡）；一名患者无需透析即可部分康复。 结论 患有 COVID-19 的黑人患者的塌陷性肾小球病与高风险 APOL1 变异相关。我们在肾脏中没有发现直接的病毒感染，这表明可能有一种替代机制：遗传易感性和细胞因子介导的宿主对 SARS-CoV-2 感染反应的“双重打击”组合。鉴于该实体与 HIV 相关肾病的相似性，我们建议用“COVID-19 相关肾病”一词来描述它。
Background Kidney involvement is a feature of COVID-19 and it can be severe in Black patients. Previous research linked increased susceptibility to collapsing glomerulopathy, including in patients with HIV-associated nephropathy, to apo L1 (APOL1) variants that are more common in those of African descent.Methods To investigate genetic, histopathologic, and molecular features in six Black patients with COVID-19 presenting with AKI and de novo nephrotic-range proteinuria, we obtained biopsied kidney tissue, which was examined by in situ hybridization for viral detection and by NanoString for COVID-19 and acute tubular injury-associated genes. We also collected peripheral blood for APOL1 genotyping.Results This case series included six Black patients with COVID-19 (four men, two women), mean age 55 years. At biopsy day, mean serum creatinine was 6.5 mg/dl and mean urine protein-creatinine ratio was 11.5 g. Kidney biopsy specimens showed collapsing glomerulopathy, extensive foot process effacement, and focal/diffuse acute tubular injury. Three patients had endothelial reticular aggregates. We found no evidence of viral particles or SARS-CoV-2 RNA. NanoString showed elevated chemokine gene expression and changes in expression of genes associated with acute tubular injury compared with controls. All six patients had an APOL1 high-risk genotype. Five patients needed dialysis (two of whom died); one partially recovered without dialysis.Conclusions Collapsing glomerulopathy in Black patients with COVID-19 was associated with high-risk APOL1 variants. We found no direct viral infection in the kidneys, suggesting a possible alternative mechanism: a "two-hit" combination of genetic predisposition and cytokine-mediated host response to SARS-CoV-2 infection. Given this entity's resemblance with HIV-associated nephropathy, we propose the term COVID-19-associated nephropathy to describe it.