Single-cell transcriptomics reveals common epithelial response patterns in human acute kidney injury

Area of Science:

• Nephrology
• Genomics
• Critical Care Medicine

Background:

• Acute kidney injury (AKI) is common in critically ill patients, leading to poor outcomes.
• The cellular mechanisms and kidney cell responses to AKI are not fully understood.

Purpose of the Study:

• To investigate the cell type-specific transcriptomic responses in human kidneys with severe AKI.
• To identify novel cellular mechanisms and injury patterns in AKI.

Main Methods:

• Single-nuclei and bulk transcriptomics on kidney tissues from 8 severe AKI patients and controls.
• Molecular imaging and conventional histology were also performed.
• Samples were collected within 1-2 hours post-mortem from critically ill patients, including 4 with COVID-19.

Main Results:

• Identified four distinct, interconnected injured cell states in tubular epithelium, linked to oxidative stress, hypoxia, interferon response, and epithelial-to-mesenchymal transition.
• Transcriptome differences were mainly due to the abundance of these cell states, not individual molecular responses.
• AKI gene expression changes were similar between COVID-19 and non-COVID-19 patients.

Conclusions:

• Provides a comprehensive resource of cell type-specific transcriptomic responses in human AKI.
• Highlights common disease signatures and individual variations in AKI.
• Suggests potential for personalized molecular assessment and tailored therapies for AKI.