WP6 Study of CRS pathology and therapy

WP6 - Study of CRS pathology and therapy [Months: 3-48]


Description and role of ESRs / beneficiaries / partner organizations:

In this WP, we will use a combination of in vitro studies, animal models and patient cohorts to examine:


Task 5.1: Novel therapeutic strategies for CRS. ESR5/RDN and ESR6/INSERM will test strategies to reduce CRS pathology in animal models, with a focus on vascular calcification. ESR5/RDN will test the effect of pep-tides CBF and VIF, recently identified by UKA1/MUW to influence vascular calcification and reactivity in vitro, on CRS in vivo. Further, ESR5/RDN and ESR6/INSERM will collaborate to study the role of newly identified CKD biomarkers in CRS pathology in animal models. These CKD biomarkers were recently identified in the EU project iMODE-CKD, and based on literature mining are associated with CV events in non-CKD patients.


Task 5.2: Reveal underlying mechanisms of increased vascular calcification and aging in CKD patients to reveal novel therapeutic strategies. ESR7/CARIM will study the effect of uremia on the phenotype and calcification potential of VSMCs and identify uremic toxins from dialysate that increase VSMC calcification in CKD patients. ESR8/UKA2 will focus on vitamin K, a crucial cofactor in the activation of the calcification inhibitor MGP: ESR8/UKA2 will examine whether vitamin K-deficiency is a mediator of vascular calcification in CKD, as UKA2 showed that high dose vitamin K administration reverts levels of uncarboxylated MGP (inactive MGP) in animal models. Of note, UKA2 recently demonstrated again its ability to coordinate multi-centre clinical trials investigating novel therapies in the context of renal disease. ESR9/DSM will identify PTMs of calcification regulators as link between CKD and CVD in CRS. ESR10/ KI will study premature vascular aging and biomarkers of vascular calcification in CKD, based on a finding of partner KI that plasma levels of sclerostin inform on vas-cular calcification in CKD patients. ESR7-10 will be trained to optimize methods to examine calcification and study animal models of CKD, CRS and vascular calcification, as well as plasma, urine and biopsies from patients.


Task 5.3: Reveal the direct effect of uremia on VSMCs and cardiomyocytes. ESR7/CARIM and ESR11/UKA1 will examine the effect of uremia on the phenotype/function of VSMCs (ESR7/CARIM) and car-diomyocytes (ESR11/ UKA1) using dialysate from CKD patients, and identify the responsible uremic toxins using chromatography and mass spectrometry in close collaboration with ESR8/UKA2 and ESR1/UKA1.


Task 5.4: Proteomics/peptidomics analyses as measure for vascular calcification and CV outcome (and thus CRS) in CKD. ESR1/UKA1 and ESR10/KI will investigate whether plasma can provide quantitative infor-mation on vascular calcification and CV outcome in CKD patients, with a focus on PTMs of calcification regula-tors (ESR9/DSM) or plasma proteins (ESR10/KI) as biomarker candidates for vascular calcification in CKD.

© 2018 CaReSyAn

  • Facebook Social Icon
  • Twitter Social Icon

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 764474.

The content of this website reflects only the views of its authors.

The European Commission is not responsible for any use that may be made of the information it contains