Open AccessSingle-Cell RNA Sequencing of Urinary Cells Reveals Distinct Cellular Diversity in COVID-19–Associated AKI
Author(s) -
Matthew D. Cheung,
Elise N. Erman,
Shanrun Liu,
Nathaniel Erdmann,
Gelare Ghajar-Rahimi,
Kyle H. Moore,
Jeffrey C. Edberg,
James F. George,
Anupam Agarwal
Publication year - 2022
Publication title -
kidney360
Language(s) - English
Resource type - Journals
ISSN - 2641-7650
DOI - 10.34067/kid.0005522021
Subject(s) - urinary system , rna , acute kidney injury , kidney , medicine , covid-19 , cell type , cell , immune system , urinary sediment , urothelial cell , biology , gene , cancer research , immunology , pathology , urothelium , genetics , disease , infectious disease (medical specialty)
Background AKI is a common sequela of infection with SARS-CoV-2 and contributes to the severity and mortality from COVID-19. Here, we tested the hypothesis that kidney alterations induced by COVID-19–associated AKI could be detected in cells collected from urine. Methods We performed single-cell RNA sequencing (scRNAseq) on cells recovered from the urine of eight hospitalized patients with COVID-19 with ( n =5) or without AKI ( n =3) as well as four patients with non–COVID-19 AKI ( n =4) to assess differences in cellular composition and gene expression during AKI. Results Analysis of 30,076 cells revealed a diverse array of cell types, most of which were kidney, urothelial, and immune cells. Pathway analysis of tubular cells from patients with AKI showed enrichment of transcripts associated with damage-related pathways compared with those without AKI. ACE2 and TMPRSS2 expression was highest in urothelial cells among cell types recovered. Notably, in one patient, we detected SARS-CoV-2 viral RNA in urothelial cells. These same cells were enriched for transcripts associated with antiviral and anti-inflammatory pathways. Conclusions We successfully performed scRNAseq on urinary sediment from hospitalized patients with COVID-19 to noninvasively study cellular alterations associated with AKI and established a dataset that includes both injured and uninjured kidney cells. Additionally, we provide preliminary evidence of direct infection of urinary bladder cells by SARS-CoV-2. The urinary sediment contains a wealth of information and is a useful resource for studying the pathophysiology and cellular alterations that occur in kidney diseases.