Project Details
Projekt
Deciphering kidney injury and repair in COVID-19-associated AKI on a single-cell level
Applicant
Dr. Christian Hinze
Subject Area
Nephrology
Term
from 2021 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 466171016
Current studies show a high number of patients with COVID-19 presenting with acute kidney injury (AKI), which is a rapid decline of kidney function. Additionally, severe COVID-associated malfunction of the kidneys is strongly associated with overall mortality of the individual patient. To date, it is poorly understood how COVID-19-associated AKI develops. A few factors which are currently discussed include 1. critical illness due to sepsis-like conditions with the need of ventilator and other life supporting treatment on intensive care units and 2. virus-specific mechanisms such as direct infection of kidney cells which can potentially damage the kidneys. We established a workflow to analyze kidney cells in critically-ill patients with COVID-19-associated AKI and Non-COVID patients with AKI due to sepsis. In these patients, we analyze kidney cells shed into the urine and from kidney biopsies of deceased patients with single-cell RNA sequencing, a new and innovative technique which enables the investigation of gene expression in thousands of individual cells, separately. From our preliminary data, we presume that general aspects of septic critical illness as well as virus-specific affection of the kidneys contribute to COVID-19-associated AKI. We believe that applying single-cell techniques to urine cells as well as to kidney biopsies from different time points of AKI will allow us to understand the pathogenesis, progression and recovery of COVID-19-associated AKI. All results in COVID patients will be systematically compared to Non-COVID patients with AKI due to sepsis. This will help to clearly distinguish the contribution of critical illness due to sepsis and virus-specific injury mechanisms in COVID-19-associated AKI. Cross correlation of urinary and kidney tissue single-cell data from different time points of AKI will allow the identification of biomarkers for therapeutic decision making, AKI progression and identify new therapeutic targets to improve outcome for the kidneys and the patient.
DFG Programme
Research Grants
