TrainCKDis brings together 9 interdisciplinary academic research teams and non-academic teams from 6 European countries and US, all internationally renowned for contributions to kidney research.
The goal of TrainCKDis is to provide high-level training in chronic kidney disease (CKD) - a global public health burden - to a new generation of highly achieving early stage researchers. TrainCKDis will develop scientific skills necessary for thriving careers in an expanding area that underpins innovative technological development across a range of diverse disciplines including nephrology, epidemiology, genetics, cell biology, and drug discovery at the interface of basic molecular, genetic and clinical research. We will achieve this by a unique combination of “hands-on” research training, non-academic placements, courses and workshops on scientific and transferable skills, facilitated by the consortium academic/non-academic composition.
A global health problem
Chronic Kidney Disease (CKD) is defined as abnormalities of kidney structure or function, lasting longer than three months. CKD is an increasing global health problem; its prevalence and associated burden are rising worldwide1. CKD affects 10-15% of the population, with unexplained regional variation across Europe. About 70 million Europeans have suboptimal kidney function and are at increased risk of kidney failure, a fatal condition without renal replacement therapies (RRT) such as dialysis or transplantation.
TrainCKDis aims to close this gap by creating a European innovative, multidisciplinary, and intersectoral training programme to prepare the next generation of top-level scientists to develop creative solutions for transforming CKD research. TrainCKDis will provide graduate students from diverse backgrounds with a broad, interdisciplinary perspective and intersectoral approach for discovery and development of new herapeutic targets and biomarkers with a particular emphasis on the role of genetics.
Key research challenges
1. Identify genetic and epigenetic modifiers that predispose patients to CKD progression
CKD progression rate varies considerably among individual patients exposed to the same risk factors. Population-based genome-wide association studies (GWAS) have recently uncovered about 100 genetic loci influencing kidney function and CKD risk. However, causal genes and variants in the reported loci often remain elusive, and have to be identified and characterized in experimental follow-up studies. Efforts to identify and characterize target genes and functional variants in associated loci must include innovative complementary strategies. In addition, whole exome sequences (WES) analysis to identify rare, functional variants requires special methods. Lastly, epigenome analysis has the potential to implicate gene regulatory mechanisms that can lead to differential gene expression in response to environmental stimuli.
2. Uncover signaling pathways and innovative biomarkers essential for monitoring disease evolution and clinical trials outcomes
Clinical trials in CKD lack early and sensitive biomarkers able (i) to identify patients at risk of faster progression who could benefit from therapy, and (ii) to monitor treatment efficacy. An ideal biomarker should reflect tissue pathology, be easily detectable by non-invasive approaches and possibly act as a critical disease player. Understanding the molecular pathways leading to CKD progression is therefore a pre-requisite for efficient biomarker development. It is unlikely that a single molecule reflects the evolution of the complex process of CKD progression. On the other hand, since the metabolome is able to reflect genetic variability, intrinsic biochemical processes and environmental challenges, its analysis is instrumental in discovering specific biomarkers. Consistently, teams of TrainCKDis have recently identified metabolites able to predict CKD progression, ready to be confirmed in broad cohorts
of CKD patients.
3. Discover novel therapeutic targets to expand the limited CKD treatments
There are few licensed treatments to slow down CKD progression. Management of CKD patients is based on controlling clinical variables known to accelerate kidney function loss, such as hypertension and hyperglycaemia. A few treatments, such as renin-angiotensin system (RAS) and sodium glucose transporter 2 (SGLT2) inhibitors have protective effects under some but not all circumstances. While these approaches provide proof-of-concept for the ability to improve CKD outcomes, no strategies have been validated that interfere directly with the pathophysiological mechanisms. Over the last 20 years, researchers have focused their efforts to uncover the molecular pathways involved in CKD progression by using experimental models of CKD. The research teams involved in TrainCKDis have played leading roles in these researches, discovering novel candidates, such as UMOD, EGF/TGF-α, HNF1B and Hypoxia Inducible Factor 1 alpha (HIF-1α). In addition, they have developed powerful experimental models that are now unique precious tools for unbiased discoveries.
- 1. Identify genetic and epigenetic modifiers that predispose patients to CKD progression