- Prof. Anette Melk, Principal Investigator
- Dr Roland Schmitt, Co-Investigator
- Mr Nathan Susnik, Research Associate
- Mrs Susanne Geerling, Study Nurse
- Mrs Margit Überheide, Technician
- PD Bernhard Schmidt, Collaborator
- Prof. Thomas Thum, Collaborator
- Prof. Volker Kliem, Collaborator
- Hannover Medical School, Hannover, Germany
- Urinary Exosome Analysis for the Study of Kidney Transplant Aging
Older kidneys have an increased susceptibility to acute and chronic disease, and the reparative function of aged kidneys is reduced when compared to younger kidneys.
Currently there is a growing use of older kidneys for transplantation due to organ shortage. Even in kidneys from young donors, it has been shown that transplantation related stress leads to molecular changes of accelerated kidney aging. These have been linked to a reduced long-term outcome. A better understanding of the underlying mechanisms is needed for developing targeted therapy. One of the most important pathways that change with aging is somatic cellular senescence (irreversible growth arrest). Somatic cellular senescence has been linked to reduced kidney function and impaired regeneration in native kidneys and in kidney transplants. So far, research on senescence in kidney transplantation has been difficult since cellular senescence can only be diagnosed in tissue biopsies. In particular, there is little known about the dynamics of how kidney cellular senescence develops after renal transplantation and how it associates with renal scarring and transplant dysfunction. Studying these issues would require many repeated biopsies of the same patient. The current project therefore aims at investigating a new noninvasive method with the goal of monitoring kidney cellular senescence in patient urine. The method relies on urinary exosome analysis. Exosomes are small membrane vesicles that are released from parental cells and contain RNA molecules that can be easily isolated and measured. As these RNA molecules closely reflect the biological function of the parental cells, urinary analysis allows monitoring molecular changes of the kidney. Our study will quantify specific RNA species that are markers of cellular senescence and of kidney scarring. By using a large set of urine from patients at different time points after kidney transplantation, we will be able to systematically compare exosome data with routine kidney biopsy results and with transplant function. Through this approach, our project will permit the evaluation of a new, easy-to-apply, non-invasive method for monitoring cellular senescence and for studying processes of molecular aging in kidney transplants.