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

Huijuan Wu1,2, Christopher P Larsen3, Cesar F Hernandez-Arroyo4

  • 1Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Journal of the American Society of Nephrology : JASN
|June 21, 2020
PubMed

Insights

Black patients with COVID-19 and collapsing glomerulopathy had high-risk APOL1 variants. Kidney injury may stem from genetic predisposition and immune response, not direct viral infection, suggesting COVID-19-associated nephropathy.

Area of Science:

  • Nephrology
  • Genetics
  • Infectious Diseases

Background:

  • COVID-19 frequently causes kidney involvement, particularly severe in Black patients.
  • APOL1 variants, common in individuals of African descent, are linked to collapsing glomerulopathy and HIV-associated nephropathy.
  • Investigating the genetic and molecular basis of severe kidney injury in Black COVID-19 patients is crucial.

Purpose of the Study:

  • To investigate genetic, histopathologic, and molecular features of acute kidney injury (AKI) and nephrotic-range proteinuria in Black patients with COVID-19.
  • To explore the role of APOL1 variants in COVID-19-associated kidney disease.
  • To identify potential mechanisms underlying kidney damage in this patient cohort.

Main Methods:

  • Case series of six Black patients with COVID-19, AKI, and de novo nephrotic-range proteinuria.
  • Kidney biopsy analysis including in situ hybridization for viral detection and NanoString gene expression profiling.
  • APOL1 genotyping from peripheral blood samples.

Main Results:

  • All six patients presented with collapsing glomerulopathy, foot process effacement, and acute tubular injury.
  • No direct viral particles or SARS-CoV-2 RNA were detected in kidney tissues.
  • Elevated chemokine gene expression and altered acute tubular injury gene profiles were observed; all patients possessed high-risk APOL1 genotypes.
  • Three patients had endothelial reticular aggregates; five required dialysis, with two deaths.

Conclusions:

  • Collapsing glomerulopathy in Black COVID-19 patients is associated with high-risk APOL1 variants.
  • The absence of direct viral infection suggests a "two-hit" mechanism involving genetic predisposition and cytokine-mediated response.
  • The proposed term COVID-19-associated nephropathy describes this entity, similar to HIV-associated nephropathy.
Abstract

Keywords:
APOL1COVID-19SARS-CoV-2collapsing glomerulopathykidney biopsynephrotic

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