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Systems biology towards novel chronic kidney disease diagnosis and treatment

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Improved future for chronic kidney disease patients

A large European consortium formulated preventive aspects, new diagnostic tools and therapeutic routes for chronic kidney disease (CKD). The interdisciplinary team specifically focused on impaired renal function associated with diabetes and hypertension.

Health

CKD is a commonly encountered disorder in industrialised countries. Kidney function is affected by many factors including diabetes and goes hand in hand with cardiovascular complications, potentially leading to end-stage renal disease (ESRD). The EU-funded SYSKID (Systems biology towards novel chronic kidney disease diagnosis and treatment) project identified lifestyle factors giving rise to recommendations for prevention. Parameters for risk factors could be used to propose optimization of diagnosis and therapy. The large range of the study has enabled comparative analysis of CKD prevalence on a Europe-wide basis. A comprehensive set of risk factors were integrated into models and used in risk scoring. The team took a data-driven approach on the molecular and cellular mechanisms of CKD. The interdisciplinary approach allowed dissecting the molecular processes that trigger CKD and developed tools for identifying individuals at risk of developing progressive disease. High-throughput analysis of genetic factors, gene expression, and protein and metabolite levels in model and human samples was carried out. This has resulted in the identification of CKD biomarker candidates associated with disease onset and progression. Large scale validation in about 2 000 samples from patients with type 2 diabetes (T2D) at different stages of CKD has been completed. SYSKID also developed novel tools to profile progressive CKD including a urinary peptide biomarker set for assessing the risk of CKD progression in T2D. Project researchers applied molecular analysis of CKD to human and disease model systems integrating all in a Systems Biology framework for identifying new ways to halt disease progression. This approach enhanced understanding of the pathophysiology of CKD, provided models for improving use of given therapies and identified novel targets to treat the disease at progressive stages. SYSKID has successfully expanded the set of molecular and clinically-based biomarkers. With enhanced knowledge of associated molecular pathways added to disease models, the research has provided key elements and tools for improving CKD-targeted drug development. Dissemination has resulted in more than 170 peer-reviewed publications, on top including a special issue of the journal NDT covering project results in a comprehensive fashion. Over 300 presentations have been made at scientific conferences including a dedicated session at the largest European renal disease conference organized by the ERA-EDTA in 2015. Moreover, updates to the project website, a regular newsletter and social media coverage have ensured the widest possible broadcast for SYSKID research results.

Keywords

Chronic kidney disease, diabetes, biomarkers, model systems, Systems Biology

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