AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL1 High-Risk Genotype Article

Full Text via DOI: 10.1681/ASN.2020050558 PMID: 32561682 Web of Science: 000558257500009
Highly Cited Paper International Collaboration

Cited authors

  • Wu, Huijuan; Larsen, Christopher P.; Hernandez-Arroyo, Cesar F.; Mohamed, Muner M. B.; Caza, Tiffany; Sharshir, Moh'd; Chughtai, Asim; Xie, Liping; Gimenez, Juan M.; Sandow, Tyler A.; Lusco, Mark A.; Yang, Haichun; Acheampong, Ellen; Rosales, Ivy A.; Colvin, Robert B.; Fogo, Agnes B.; Velez, Juan Carlos Q.


  • 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.

Publication date

  • 2020


International Standard Serial Number (ISSN)

  • 1046-6673

Start page

  • 1688

End page

  • 1695


  • 31


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