Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
J Am Soc Nephrol. 2020 Aug;31(8):1688-1695. doi: 10.1681/ASN.2020050558. Epub 2020 Jun 19.
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 () variants that are more common in those of African descent.
To investigate genetic, histopathologic, and molecular features in six Black patients with COVID-19 presenting with AKI and nephrotic-range proteinuria, we obtained biopsied kidney tissue, which was examined by hybridization for viral detection and by NanoString for COVID-19 and acute tubular injury-associated genes. We also collected peripheral blood for genotyping.
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 high-risk genotype. Five patients needed dialysis (two of whom died); one partially recovered without dialysis.
Collapsing glomerulopathy in Black patients with COVID-19 was associated with high-risk 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.
肾脏受累是 COVID-19 的一个特征，在黑人患者中可能较为严重。先前的研究表明，与 HIV 相关肾病患者的易发性增加相关的陷窝性肾小球病，包括 apo L1 () 变体在非洲裔人群中更为常见。
为了研究 6 例 COVID-19 黑人患者的遗传、组织病理学和分子特征，这些患者表现为 AKI 和肾病范围蛋白尿，我们获得了活检肾组织，该组织通过 杂交进行病毒检测，通过 NanoString 进行 COVID-19 和急性肾小管损伤相关基因检测。我们还收集了外周血进行 基因分型。
该病例系列包括 6 例 COVID-19 黑人患者（4 名男性，2 名女性），平均年龄为 55 岁。在活检日，平均血清肌酐为 6.5mg/dl，尿蛋白/肌酐比值为 11.5g。肾脏活检标本显示陷窝性肾小球病、广泛的足突消失和局灶性/弥漫性急性肾小管损伤。3 例患者有内皮网状聚集物。我们没有发现病毒颗粒或 SARS-CoV-2 RNA 的证据。NanoString 显示趋化因子基因表达升高，与对照组相比，与急性肾小管损伤相关的基因表达发生变化。所有 6 例患者均有 高风险基因型。5 例患者需要透析（其中 2 例死亡）；1 例未经透析部分恢复。
COVID-19 黑人患者的陷窝性肾小球病与高风险 变体有关。我们在肾脏中没有发现直接的病毒感染，这表明可能存在另一种机制：遗传易感性和细胞因子介导的宿主对 SARS-CoV-2 感染的反应的“双重打击”组合。鉴于该实体与 HIV 相关肾病的相似性，我们建议使用 COVID-19 相关肾病来描述它。
