Resilience against kidney damage

Principal Investigator

Scientific interest within the context of the graduate college:

Our research group focuses on the complex interactions between immune cells and kidney epithelial cells. By analyzing cells found in urine, examining kidney biopsy samples, and utilizing cell culture models, we aim to gain deeper insights into the mechanisms underlying kidney injury and repair. Our work centers on the study of human patient samples, allowing us to address the fundamental question of how kidneys are damaged during disease and how they recover following injury.

Project description:

Kidney damage, in the acute form as acute kidney injury (AKI) or the chronic form as chronic kidney disease (CKD), is among the most frequent forms of organ damage. AKI and CKD both have a tremendous impact and are associated with increased morbidity and mortality, having a large negative impact on global health. In the proposed project we are interested in cellular mechanisms protecting us from kidney injury. Based on our previous observation, immune and kidney tubular epithelial cells can be found in the urine and correlate with damage in AKI and inflammation in CKD.^1,2 These cells phenotypically resemble tissue cells, and can be used as a “window into the kidney” to understand pathophysiological processes non-invasively.^1,3 Interestingly, increased amounts of immune and tubular epithelial cells can also be observed in critically ill patients without AKI and in stable CKD patients. At present it is unclear, whether these cells just reflect subclinical damage not detected by standard markers, or whether they reflect an active adaptation to kidney stress. Therefore, we will use a combination of state-of-the-art methods such as single-cell RNA sequencing (scRNAseq) and flow cytometry, aiming to understand which active cellular adaptation protects us from kidney damage. All required cohorts and techniques are established in our group.

WP1: Determine the gene expression of kidney tubular epithelial cells in patients without kidney damage. We will use scRNAseq of immune and kidney tubular epithelial cells excreted in the urine of patients without kidney damage. The patients will include critically ill patients without AKI and patients with stable CKD. The respective data will be compared to our existing data sets from patients with active kidney damage (AKI and different forms of other kidney diseases). This WP will yield differences in cell composition and gene expression between active kidney damage and stable kidney function.

WP2: Derive a flow cytometry panel from scRNAseq data. Based on the differences in cell composition and transcriptomes in WP1, we will establish an antibody-based staining panel to detect the respective differences using flow cytometry. This will enable us to analyze a larger cohort of patients in the subsequent WP.

WP3: Active and failed adaptation to kidney stress. We will use flow cytometry and the staining developed in WP2 to assess a larger cohort of patients with kidney stress over time. The cohort will include CKD patients with and without stable kidney function as well as critically ill patients with and without AKI.

Application details

References