Molecular Analysis of the Kidney From a Patient With COVID-19–Associated Collapsing Glomerulopathy

Kristin Meliambro, Xuezhu Li, Fadi Salem, Zhengzi Yi, Zeguo Sun, Lili Chan, Miriam Chung, Jorge Chancay, Ha My T. Vy, Girish Nadkarni, Jenny S. Wong, Jia Fu, Kyung Lee, Weijia Zhang, John C. He, Kirk N. Campbell

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Recent case reports suggest that coronavirus disease 2019 (COVID-19) is associated with collapsing glomerulopathy in African Americans with apolipoprotein L1 gene (APOL1) risk alleles; however, it is unclear whether disease pathogenesis is similar to HIV-associated nephropathy. RNA sequencing analysis of a kidney biopsy specimen from a patient with COVID-19–associated collapsing glomerulopathy and APOL1 risk alleles (G1/G1) revealed similar levels of APOL1 and angiotensin-converting enzyme 2 (ACE2) messenger RNA transcripts as compared with 12 control kidney samples downloaded from the GTEx (Genotype-Tissue Expression) Portal. Whole-genome sequencing of the COVID-19–associated collapsing glomerulopathy kidney sample identified 4 indel gene variants, 3 of which are of unknown significance with respect to chronic kidney disease and/or focal segmental glomerulosclerosis. Molecular profiling of the kidney demonstrated activation of COVID-19–associated cell injury pathways such as inflammation and coagulation. Evidence for direct severe acute respiratory syndrome coronavirus 2 infection of kidney cells was lacking, which is consistent with the findings of several recent studies. Interestingly, immunostaining of kidney biopsy sections revealed increased expression of phospho-STAT3 (signal transducer and activator of transcription 3) in both COVID-19–associated collapsing glomerulopathy and HIV-associated nephropathy as compared with control kidney tissue. Importantly, interleukin 6–induced activation of STAT3 may be a targetable mechanism driving COVID-19–associated acute kidney injury.

Original languageEnglish
Pages (from-to)653-658
Number of pages6
JournalKidney Medicine
Volume3
Issue number4
DOIs
StatePublished - 1 Jul 2021

Keywords

  • APOL1
  • COVID-19
  • Collapsing glomerulopathy
  • FSGS
  • IL-6
  • STAT3

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