PRECISE

Idiopathic Nephrotic Syndrome (INS) is a rare paediatric glomerular disease, requiring an intense treatment with glucocorticoids and other immunosuppressive drugs. The disease has an extremely variable clinical behaviour, with 10-15% of patients remaining unresponsive to immunosuppressive treatment and facing the risk of requiring kidney replacement therapy. Although the largest portion of children are steroid-sensitive, their clinical course is challenging, characterised by continuous relapses, and demanding for long-lasting treatments, with major side effects. There are no established clinical or biochemical markers to predict the response to treatment and the occurrence of relapses. 

The overall goal of the PRECISE project is the identification of novel non-invasive prognostic biomarkers, using urine and blood as “liquid biopsies” in a large pan-European paediatric clinical cohort. The pathogenesis of INS is still not fully understood. As dysregulation of both T-and B-cell function as well as cytokine imbalance are known to play a critical role, we will combine immune cell profiling by spectral flow cytometry, single-cell RNA sequencing, and a deep multi-omics analysis of the biofluids’ secretome (vesicular and non-vesicular). These data, in association with a genetic/epigenetic lineage tracing, will allow a clear definition of the lymphocyte’s alteration in the various forms of INS. Lastly omics data, generated within the consortium, will be integrated in a single analytical framework to generate clinically relevant prediction models, based on the clinical course of the disease. This will allow for a more adequate tailoring of treatments.