Single-Cell RNA Sequencing of Urinary Cells Reveals Distinct Cellular Diversity in COVID-19-Associated AKI.
Matthew D Cheung, Elise N Erman, Shanrun Liu, Nathaniel B Erdmann, Gelare Ghajar-Rahimi, Kyle H Moore, Jeffrey C Edberg, James F George, Anupam Agarwal
Author Information
Matthew D Cheung: Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama. ORCID
Elise N Erman: Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
Shanrun Liu: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
Nathaniel B Erdmann: Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
Gelare Ghajar-Rahimi: Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama. ORCID
Kyle H Moore: Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama. ORCID
Jeffrey C Edberg: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
James F George: Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama.
Anupam Agarwal: Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama. ORCID
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 (=5) or without AKI (=3) as well as four patients with non-COVID-19 AKI (=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. and 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.
