A New Approach of Assessing Acute Kidney Injury in Patients: urinary microRNAs

• Applicant: Dr. Mira Pavkovic
• Subject Area: Nephrology ; Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2015 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 289298815

Biomarkers (BMs) are indicators of diseases. For acute kidney injury (AKI) in humans sensitive and specific BMs are missing which could enable an early, reliable and non invasive diagnosis. MicroRNAs (miRs) are small nucleic acids regulating gene expression (occurrence of genetic information) inside cells but can also be found in body fluids (urine, blood). Latter displays them as promising BMs, since they are stable and easily accessible there. Furthermore, they are already associated with diverse diseases. The objective of the research project is the evaluation of urinary miRs as BM candidates for AKI in humans and the investigation of their role in onset and progression of kidney injury.Based preliminary data, 358 miRNA biomarker candidates have been identified using a well-defined cohort of patients with drug-induced kidney injury. Among these candidate miRs, potential BMs will be those that can indicate AKI early (sensitivity), precise (accuracy) and distinct (specificity). The basis of this BM evaluation is the comparison of levels of miRs in urine of patients without and with AKI at different stages of development. A following comparison to established kidney BMs will be performed in order to analyze the sensitivity and accuracy of the potential urinary miR-BM. A co-localization with injured tissue in the kidney reflects their feature as organ and injury specific BMs. Therefore the localization of confirmed candidate miRs will be investigated in kidney tissue. The elucidation of the miRs involvement in molecular processes during AKI increases the understanding of AKI onset and progression, and could build a basis for therapy approaches later on. Accordingly, miR targets (genes or rather more precise mRNAs) will be identified thereby discovering also affected networks and pathways.For conduction of the proposed research project urine and kidney biopsy samples from diverse well-conducted clinical studies are available in my host laboratory. Urinary and kidney will be measured using a sensitive and for nucleic acids commonly used detection method (quantitative real-time PCR). The localization of miRs in kidney tissue will be identified by a method visualizing nucleic acids in tissue sections (in situ hybridization). If urinary miRs prove to be sensitive and specific BMs for AKI, a regulatory qualification will be conceivable. Their application would enable an early and distinct diagnosis thus avoiding the development of end stage renal diseases associated with high mortality risks.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Vishal S. Vaidya, Ph.D.