期刊
KIDNEY INTERNATIONAL
卷 102, 期 6, 页码 1359-1370出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2022.07.032
关键词
acute kidney injury; distal tubule; gene expression
资金
- Berlin Institute of Health
- Jackstadt-Stiftung
- Deutsche Forschungsgemeinschaft (DFG) [HI 2238/2-1, SFB 1365, GRK 2318, FOR 2841]
- Bundesministerium fur Bildung und Forschung
- Deutsche Gesellschaft fur Nephrologie
This study demonstrates the feasibility and potential of using urine for single-cell transcriptomics to investigate the cellular and molecular dynamics of acute kidney injury (AKI). The findings provide unprecedented insights into the processes underlying AKI and open up new opportunities for target identification, sub-categorization, and monitoring of the disease.
Acute kidney injury (AKI) is a major health issue, the outcome of which depends primarily on damage and reparative processes of tubular epithelial cells. Mechanisms underlying AKI remain incompletely understood, specific therapies are lacking and monitoring the course of AKI in clinical routine is confined to measuring urine output and plasma levels of filtration markers. Here we demonstrate feasibility and potential of a novel approach to assess the cellular and molecular dynamics of AKI by establishing a robust urine-to-single cell RNA sequencing (scRNAseq) pipeline for excreted kidney cells via flow cytometry sorting. We analyzed 42,608 single cell transcriptomes of 40 urine samples from 32 patients with AKI and compared our data with reference material from human AKI postmortem biopsies and published mouse data. We demonstrate that tubular epithelial cells transcriptomes mirror kidney pathology and reflect distinct injury and repair processes, including oxidative stress, inflammation, and tissue rearrangement. We also describe an AKI-specific abundant urinary excretion of adaptive progenitor-like cells. Thus, single cell transcriptomics of kidney cells excreted in urine provides noninvasive, unprecedented insight into cellular processes underlying AKI, thereby opening novel opportunities for target identification, AKI sub-categorization, and monitoring of natural disease course and interventions.
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