Center for Molecular Medicine Cologne

Small urinary extracellular vesicles: a new source of biomarkers to monitor kidney transplant adaptation


A team of scientists identified a novel non-invasive method to predict outcome after kidney transplantation in urine in an interdisciplinary setting at the Medical Faculty of the University of Cologne and University Hospital of Cologne


Prof. Dr. Roman Ulrich Müller states: "The study is a result of an intensive interdisciplinary collaboration between basic researchers and clinician-scientists showing clearly the clinical translation and the impact on a better treatment for human diseases".

Chronic kidney disease has emerged as one of the major health problems and cost factors for health care systems worldwide affecting all age groups. Kidney transplantation is considered the treatment of choice for end-stage renal disease resulting in benefits both regarding survival and quality of life compared to dialysis. However, there are not enough donors available for the large number of patients with kidney disease. In addition transplant rejection and chronic allograft nephropathy are decreasing organ survival causing a need for repetitive transplantation. Therefore, understanding the molecular processes in the kidney after transplantation to maintain optimal organ function is crucial for improving allograft outcome.

Currently the diagnosis of the underlying disorder relies primarily on renal biopsy via hollow needle tissue sampling involving both a bleeding risk with possible organ damage and the potential of misdiagnosis due to sampling errors. Besides, tissue for studies on cell biology in transplantation is limited.

Urine is considered as an optimal biomaterial being easily available for scientific characterization and diagnosis of kidney diseases. However, due to lack of suitable methods, it has been insufficiently used so far. In recent years, urinary extracellular vesicles (EVs) - actively secreted by nephron‐lining epithelial cells - have shifted into the research focus for reflecting the cellular biology more directly.

An interdisciplinary team of scientists working in the field of nephrology at the Clinic II of Internal Medicine and the Clinic for Transplantation Medicine at the Medical Faculty of Cologne and the University Hospital Cologne as well as affiliated with the Cluster of Excellence for Aging Research CECAD and the Center for Molecular Medicine Cologne (CMMC) have now succeeded in making significant progress in this area.

‚We are extremely happy. Our data provide an excellent basis for a better understanding of the adaptation process of kidney transplants and highlight the potential of suEVs as a source of biomarkers for predicting renal function during diseases. The study is the result of an intensive interdisciplinary collaboration between basic researchers and clinician-scientists showing clearly the clinical translation and the impact on a better treatment for human diseases,‘ comments study leader Prof. Roman-Ulrich Müller, Clinic II for Internal Medicine.

Using mass spectrometry (MS) the proteome of so-called small urinary extracellular vesicles (suEVs) in urine in two cohorts of 22 kidney donors and 22 kidney recipients in the context of live kidney transplantation was analysed for the first time. Unbiased proteomic analysis revealed temporal patterns of suEV protein signature and cellular processes involved in both early response and longerterm graft adaptation. Complement activation was among the most dynamically regulated components.

The resulting data set represents a novel and unique atlas of the suEV proteome (available online) providing an insight into biological processes involved throughout transplantation. Additionally, a correlative analysis identified putative prognostic markers of future allograft function. One of these markers – phosphoenol pyruvate carboxykinase (PCK2) – could be confirmed using targeted MS in an independent validation cohort of 22 additional patients.

This study recently published in the renowned Journal of Extracellular Vesicle demonstrates the impact of kidney transplantation on urinary EVs composition, which provide information to early molecular processes in transplant biology. Furthermore, the data highlight the potential of suEVs as a source of biomarkers.

Original Publication:
The proteomic landscape of small urinary extracellular vesicles during kidney transplantation
Fabian Braun, Markus Rinschen, Denise Buchner, Katrin Bohl, Ingo Plagmann, Daniel Bachurski, Martin Richard Späth, Philipp Antczak, Heike Göbel, Corinna Klein, Jan‐Wilm Lackmann, Oliver Kretz, Victor G. Puelles, Roger Wahba, Michael Hallek, Bernhard Schermer, Thomas Benzing, Tobias B. Huber, Andreas Beyer, Dirk Stippel, Christine E. Kurschat, Roman‐Ulrich Müller
Journal of Extracellular Vesicles:  First published: 19 November 2020

Scientific contact:
Prof. Dr. Roman-Ulrich Müller
Clinic II of Internal Medicine
Nephrolab Cologne | Kindey Research Center Cologne
affiliated with CECAD and CMMC