The urgent need for translational research in each of these three focus areas will be addressed by the three Primary Research Projects as well as by the three Research Cores, all proposed by outstanding funded investigators with a track record of successful multidisciplinary collaborative efforts in the focus areas.

Project 1: Integration of Risk Stratification, Biomarkers, and Functional Testing to Direct Care in Children with AKI – Dr. Stuart Goldstein (PI)

The overarching aim of this project is to operationalize an immediate renal angina index (RAI) detection/reporting system to direct standardized NGAL assessment and diuretic challenge to personalize care in critically ill children at high risk of severe AKI development as well as recovery from AKI. We have developed three interrelated specific aims to utilize the core resources of this P50 grant to fulfill this goal:

A1. This aim will utilize the RAI-NGAL clinical decision tool to direct a standardized assessment of a response to furosemide, termed the “Furosemide Stress Test (FST)”, in critically ill children.

A2. This aim will determine if a positive RAI-NGAL-FST profile can predict which critically ill children will ultimately develop significant (>10%) positive ICU fluid accumulation for more than 24 hours and thereby optimize RRT initiation.

A.3. This aim will determine if the peak and/or duration of elevated urinary NGAL levels predict duration of AKI and onset of recovery from AKI, and will evaluate proteomic profiles for discovery of novel biomarkers to predict the AKI recovery.

Project 2: Targeting Pathologic Fibronectin in Renal Fibrosis – Drs. Burns Blaxall and Prasad Devarajan (Co-PI's)

The overarching aim of this project is to determine whether inhibition of fibronectin (FN) polymerization attenuates cardiorenal injury by limiting pathologic fibroblast activation and interstitial organ fibrosis:

A1. To determine the efficacy and specificity of inhibiting FN polymerization and/or ablating fibroblast-restricted FN expression in attenuating the progression of renal injury in cardiorenal syndrome.

A2. To determine the mechanism(s) of inhibiting FN polymerization and/or ablating FN expression in attenuating cardiac or kidney fibroblast activation.