The objectives are to identify and validate candidate biomarkers and/or biomarker panels from existing longitudinal databases. Enhance the understanding of key driver pathways that accelerate progression of DKD, as well as pathways that enable & drive the pathogenesis of DKD in the overall context of diabetes itself. Asses differences between DKD associated with Type 1 DM and Type 2 DM. In parallel with this early work in biomarker identification and profiling of people with DKD, preclinical efforts will leverage longitudinal clinical database findings to identify better in vitro and in vivo models of DKD, identify predictive biomarkers for both efficacy and safety, and identify new druggable target pathways for future drug development. The overarching goal is to provide therapeutic developers with new tools that are acceptable to global regulators to enable and facilitate drug development (e.g. companion diagnostics).
Worldwide, diabetic kidney disease (DKD) is the leading cause of end stage renal disease (ESRD), and its global incidence and prevalence are increasing. The 5-year survival of a dialysis patient with DKD is less than 25 percent—worse than most cancers—new treatments are desperately needed to slow and/or reverse disease in this high-risk patient population. In order for DKD trials to be more successful in the future, the research community will need to advance a concerted effort to identify personalized markers to identify patients at high risk of progression, to identify patient subpopulations that are likely to respond to candidate therapeutics and to provide early indications of potential safety issues linked to candidate therapeutic agents.
The overall Project is expected to significantly advance the understanding of the pathophysiology, heterogeneity and natural history of DKD in patients, improve the knowledge on translatable preclinical models for DKD, and facilitate the development of standardized biomarker panels with both prognostic and predictive capacity to serve as entry criteria for future clinical trial protocols evaluating novel therapies for DKD.