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Multi-markers risk assessment of kidney sensitivity to injury to personalize prevention of acute kidney injury (SPAREKID)

Acute kidney injury (AKI) is a life-threatening disease with high mortality characterized by an abrupt decrease of the kidney glomerular filtration rate, extra-kidney consequences (cardiovascular diseases, lung injury, neurological impairment) and high risk of secondary chronic kidney disease. The cost of AKI is very high and substantial cost savings may be yielded by the development of new preventive and management strategies. SpareKid aims to predict the development of AKI to allow dedicated primary prevention.
AKI is an extremely complex disease perfectly exemplified by the current inability to successfully predict the development of AKI before the attack, even in a well-controlled clinical setting such as cardiac surgery or chemotherapy. The complexity of AKI leads to a huge heterogeneity of the kidney response even after an insult of similar intensity, which strongly impedes the personalized management of individuals in AKI at-risk situations. These data also suggest that AKI should be better described as a maladaptive kidney response to the insult. Therefore, the first innovative concept of SpareKid is to define a so-called non-invasive Kidney Resilience Index (KRI). The second innovative concept of SpareKid is to define the KRI based on in-depth and multiscale molecular and clinical data using a holistic big data-based strategy to integrate high throughput urinary and plasma proteomic, immunologic signatures (bulk-RNA sequencing and characterization of immune cell populations), and genetic signatures (whole-genome sequencing) and detailed clinical parameters. Last, using data from the National Systems of Health to model the potential cost-effectiveness of new predictive algorithms developed, we will assess the cost of each clinical trajectory according to the outcomes (AKI, CKD, death) of patients, the cost sparing of a preventive strategy and ultimately proposed a new methodology for randomized clinical trials in AKI to improve their cost-effectiveness.