I nyreteamet ved urologisk afdeling på Aarhus Universitetshospital bestræber vi os på at forbedre resultaterne og livskvaliteten for patienter med nyresygdomme, der kan behandles kirurgisk. I vores daglige praksis dækker vi alle områder for diagnostisk undersøgelse, kirurgisk og ablativ behandling af nyretumorer. Derudover behandler vi også patienter med kronisk nyresvigt, som har brug for dialyse eller nyretransplantation.
Vores forskning i nyreteamet dækker alle ovenstående aspecter, specielt med fokus på at forbedre slutresultatet for patienterne efter nyretransplantation, nyrekræft og nyrefibrose. Vores forskning laves gennem kliniske studier, og store eksperimentelle dyreforsøg, som udføres i tværfaglige samarbejder med lokale- og internationale grupper inden for dette område.
PRE-IMAGE: PREPAIR-1: Physiology of Renal Ex vivo Perfusion for organ Assessment and Injury Repair – 1
The PRE-IMAGE project aims to determine the molecular mechanisms of ex vivo kidney perfusion prior to renal transplantation in order to develop breakthrough pre-transplant perfusion-based diagnostic markers that can indicate kidney transplant outcomes and to establish the added value of pre-transplant normothermic ex vivo kidney perfusion. (Pre-IMAGE.eu)
PREPAIR-1
Physiology of Renal Ex vivo Perfusion for organ Assessment and Injury Repair – 1 is carried out in Aarhus University Hospital. In PREPAIR-1, a preclinical model will be utilized to identify molecular biomarkers that define the effect of ex vivo normothermic perfusion on porcine kidneys and how ex vivo perfusion differs from a kidney perfused in vivo. First, both kidneys of each animal are imaged in vivo in an MRI scanner, while under general anesthesia. Next, both kidneys are surgically retrieved and perfused ex vivo. One kidney of each pair will be exposed to warm ischemic injury. From both kidneys, tissue biopsies and circulating perfusate / blood samples will be taken just prior to retrieval and, subsequently, each hour during ex vivo perfusion. Radiological data are obtained while the anesthetized pig and the ex vivo machine are placed in an MRI scanner. Molecular multi-omics and radiomics analyses will be performed. Ex vivo and in vivo findings will be longitudinally contrasted in order to characterize the typical effect that ex vivo perfusion has on an isolated kidney.
Collaboration
The project is a collaboration between Department of Organ Donation and Transplantation, University Medical Center Groningen, The Department of Urology, Aarhus University Hospital The department of nephrology, Aarhus University Hospital and The MR Research Center, Aarhus University,
Contact
PhD student Tim Hamelink (t.l.hamelink@umcg.nl)
Anna Krarup Keller (anna.keller@clin.au.dk), Department of Urology
Title
Precision-cut kidney slices: a translational model of renal fibrosis
Aim
Renal fibrosis, characterized by the excessive deposition of extracellular matrix proteins, is a driver of progressive chronic kidney diseases. During disease progression, fibrotic lesions replace functional tissue ultimately resulting in organ failure, necessitating the need for renal replacement therapy or renal transplantation. To date, anti-fibrotic therapeutics are hardly available, and drug development is impeded by the lack of appropriate cell and animal models to study human fibrosis. In vitro models lack cellular heterogeneity, which is a prerequisite to mimic the multicellular character of fibrosis, while animal models often do not recapitulate human pathophysiology. To overcome these issues, our lab uses human precision-cut kidney slices (PCKS) to study renal fibrosis and as drug-screening platform.
Method/description
PCKS is a unique model that is more physiologically relevant as compared to most of the currently used in vitro systems. Each slice contains all cell types and acellular components of the whole organ in the original configuration, while preserving cell-cell and cell‐matrix interactions. In other words, PCKS are miniaturized organs that retain native tissue architecture and intact cellular environment, making it an extremely useful model to elucidate the process of fibrogenesis and to accelerate the search for effective anti-fibrotics. In our lab, PCKS are prepared from human renal tissue obtained from either 1) tumor nephrectomies – selecting for macroscopically healthy cortical tissue or 2) end-stage renal disease nephrectomies/transplantectomies. The first group is regarded as healthy and can be used to study the onset of renal fibrosis, while the second group is used to study established fibrosis. In short, PCKS is a useful and versatile translational tool to study renal (patho)physiology.
Collaboration
The project is a collaboration between Departments of Clinical Medicine, Biomedicine, iNANO, Aarhus University, and The Department of Urology, Aarhus University Hospital.
Contact
Associate Professor Rikke Nørregaard, RN@clin.au.dk
Assistant Professor Henricus A.M. Mutsaers, h.a.m.mutsaers@clin.au.dk, Department of Clinical Medicin
Mia Gebauer Madsen, miamadse@rm.dk or www.norregaardlab.com, Department of Clinical Medicine
Anna Krarup Keller, anna.keller@clin.au.dk, Department of Urology