Acute kidney injury-associated renal epithelial cell states as therapeutic targets and biomarkers of injury and repair

• Applicants: Professor Dr. Christian Hinze; Dr. Jan Klocke
• Subject Area: Nephrology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 561833001

Acute kidney injury (AKI) is a critical medical condition that frequently affects hospitalized patients. It represents a significant burden on both individual patients and the healthcare system, with costs that often surpass those associated with most cancer diagnoses. Despite its severe impact on key outcomes, such as increased patient mortality, and the substantial economic implications, treatment options for AKI remain largely limited to best supportive care. This lack of targeted therapies is primarily due to an incomplete understanding of AKI pathophysiology. However, the recent advances in high-resolution transcriptomics offer hope for a deeper molecular understanding and the potential development of targeted AKI treatments. Our team and other researchers have utilized single-cell transcriptomics to study AKI-affected kidney tissue, revealing the emergence of specific AKI-associated cell populations. These populations include injured epithelial cells that can be identified not only within the kidney tissue but also in patient urine. Within these injured cells, a subset stands out due to its severe damage. These cells exhibit characteristics of epithelial-mesenchymal transition (EMT), displaying a pro-fibrotic and pro-inflammatory profile that attracts leukocytes and fibroblasts to injury sites and impacts nearby healthy tubular epithelial cells. Due to their persistence, these EMT cells contribute to ongoing kidney damage and promote the progression to organ fibrosis. Drawing from our comprehensive preliminary data, we aim to leverage these severely injured tubular epithelial cells (EMT TECs) as both biomarkers and therapeutic targets for AKI. For biomarker purposes, EMT TECs indicate irreversible kidney damage, with their presence and quantity correlating to the extent of injury. These cells can be isolated and quantified from patient urine samples. As therapeutic targets, we seek to mitigate the harmful crosstalk between these EMT TECs and healthy kidney epithelium, focusing initially on CD44 signaling pathways identified in our preliminary findings. In conclusion, the use of single-cell and spatial transcriptomics presents an opportunity to significantly advance the field of AKI research. The analysis of urine-derived EMT TECs offers a cutting-edge and promising approach to assess AKI severity and uncover novel therapeutic strategies.

• DFG Programme: Research Grants