Kleine bloedvaten, grote problemen: microvasculaire dysfunctie in chronisch nierlijden

hronic kidney disease (CKD) is a progressive condition associated with an exceptionally high risk of cardiovascular (CV) complications and one of the leading causes of mortality worldwide. Progressive CKD is increasingly recognized as a microvascular disease characterized by microvascular rarefaction, impaired vasoreactivity and fibrotic remodeling. Systemic microvascular endothelial dysfunction (MVD) is on the crossroad between CKD progression and CV risk. Novel biomarkers to detect early MVD at a reversible stage offer a unique opportunity to prevent further CKD progression. We aim to 1) improve early diagnosis of MVD in CKD by focusing on the novel non-invasive assessment dynamic retinal vessel analysis (DVA); 2) to establish the central role of in vivo assessment of MVD in clinical decision making i.e. prediction of CKD progression as well as prediction of individual response to exercise training and 3) to identify candidate therapeutic targets for early MVD. We will integrate results from observational and interventional clinical studies in CKD and kidney transplant recipients. Transcriptomic signatures of renal endothelial cells will be studied at the single cell level and novel therapeutic targets for MVD will be validated in a representative mouse model exploiting a novel EC-specific lipid nanoparticles technique (REVOLT). This project paves the way for better outcomes for CKD patients, and, by extension, other patients with chronic diseases at high CV risk.