Integrative Biology of Diabetic Kidney Disease.

BACKGROUND: The leading cause of ESRD in the U.S. is diabetic kidney disease (DKD). Despite significant efforts to improve outcomes in DKD, the impact on disease progression has been disappointing. This has prompted clinicians and researchers to search for alternative approaches to identify persons at risk, and to search for more effective therapies to halt progression of DKD. Identification of novel therapies is critically dependent on a more comprehensive understanding of the pathophysiology of DKD, specifically at the molecular level. A more expansive and exploratory view of DKD is needed to complement more traditional research approaches that have focused on single molecules.

SUMMARY: In recent years, sophisticated research methodologies have emerged within systems biology that should allow for a more comprehensive disease definition of DKD. Systems biology provides an inter-disciplinary approach to describe complex interactions within biological systems including how these interactions influence systems' functions and behaviors. Computational modeling of large, system-wide, quantitative data sets is used to generate molecular interaction pathways, such as metabolic and cell signaling networks.

KEY MESSAGES: Importantly, interpretation of data generated by systems biology tools requires integration with enhanced clinical research data and validation using model systems. Such an integrative biological approach has already generated novel insights into pathways and molecules involved in DKD. In this review, we highlight recent examples of how combining systems biology with traditional clinical and model research efforts results in an integrative biology approach that has significantly added to the understanding of the complex pathophysiology of DKD.