AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL 1 High-Risk Genotype

J Am Soc Nephrol. 2020 Aug;31(8):1688-1695. doi: 10.1681/ASN.2020050558. Epub 2020 Jun 19.


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.

Keywords: APOL1; COVID-19; SARS-CoV-2; collapsing glomerulopathy; kidney biopsy; nephrotic.

MeSH terms

  • Acute Kidney Injury / complications
  • Acute Kidney Injury / genetics*
  • Adult
  • Aged
  • Alleles
  • Apolipoprotein L1 / genetics*
  • Biopsy
  • Black People
  • COVID-19
  • Coronavirus Infections / complications
  • Coronavirus Infections / genetics*
  • Creatinine / blood
  • Female
  • Genotype
  • Humans
  • Kidney / pathology
  • Kidney Glomerulus / physiopathology
  • Kidney Glomerulus / virology*
  • Kidney Tubules / pathology
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / genetics*
  • Risk


  • APOL1 protein, human
  • Apolipoprotein L1
  • Creatinine