Project description DEENESFRITPL Feedback on chronic kidney disease Kidneys play a critical role in maintaining good health, clearing excess water and waste from blood to prevent toxic build-up. To do this, each kidney has about a million tiny filtering 'units' comprising a glomerulus and a tubule. Scarring of kidney tissues is a hallmark of chronic kidney disease but the mechanisms are unclear. DIE_CKD researchers suspect a novel feedback pathway between the glomeruli and the tubules is involved in scarring of kidney tissue. Transgenic mice and human renal biopsies will help them test their hypothesis. Show the project objective Hide the project objective Objective Chronic kidney disease (CKD) is a major cause of morbidity and mortality, affecting over 10 % of the adult population. Regardless of the primary case, the progressed stage is characterized by scarring of all anatomical elements of the kidney - glomeruli, tubulointerstitium, and vasculature, referred to as renal fibrosis. Tubulointerstitial fibrosis has largely been viewed as a consequence of glomerular scarring, reflecting hypoxia downstream from the scarred glomeruli. Novel data suggest that an ongoing communication between the glomerular and tubular compartments (tubuloglomerular feedback) plays an important role in the progression of renal fibrosis. Particularly, injury to the tubular compartments leads to more pronounced glomerular injury in the future. DIE_CKD is designed to uncover the range and mechanisms of tubular injuries involved in the pathogenic tubuloglomerular feedback. To achieve the project objectives, double/quadruple transgenic mice with the possibility of time-dependent, subsequent injury to different compartments of the kidney will be used. This unique approach will enable a direct study of how the injury to tubular compartments predisposes glomeruli to more severe injury. Detailed analysis of the mechanisms behind these effects will be performed. The experimental data will be further confirmed in human renal biopsies of patients with Fabry disease with progressed CKD and renal fibrosis. Comprehensive histopathological assessment of long-term prognosis of sequential biopsies will be performed to analyze the involvement of individual compartments over time. Fields of science social sciencessociologydemographymortalitymedical and health sciencesclinical medicinenephrologykidney diseases Keywords chronic kidney disease renal fibrosis PAI-1 Fabry nephropathy Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator UNIVERSITETET I BERGEN Net EU contribution € 266 345,28 Address Museplassen 1 5020 Bergen Norway See on map Region Norge Vestlandet Vestland Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Partners (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all Partner Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement. VANDERBILT UNIVERSITY United States Net EU contribution € 0,00 Address West end avenue 2201 37235 Nashville tenessee See on map Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 165 265,92