Investigating the Transition from AKI to CKD in Young Children
July 25, 2025
Takuto Chiba, PhD, research assistant professor in the Division of Pediatric Nephrology at UPMC Children’s Hospital of Pittsburgh, has received a 2025 Children’s Hospital of Pittsburgh Foundation Children’s Trust Grantmakers award to advance his research on the mechanisms that drive progression from acute kidney injury (AKI) to chronic kidney disease (CKD), particularly in neonates and young children.
Children's Trust is a group of rising philanthropists that collectively channels their philanthropic passions and energies in support of UPMC Children’s most promising pediatric researchers. Over the past ten years, Children's Trust has awards 18 research grants and contributed $770,000 towards pediatric research.
Dr. Chiba’s research focuses on the role of pericytes. Pericytes are specialized mesenchymal cells that normally support the kidney’s microvasculature in the development of fibrosis following AKI. In response to injury, pericytes detach from capillaries and transform into myofibroblasts, a cell type that drives scarring and loss of kidney function. This maladaptive transition plays a central role in the AKI-to-CKD continuum.
“Infants and very young children are uniquely susceptible to long-term kidney complications following AKI, and we need better tools to understand and mitigate those risks,” says Dr. Chiba.
Uncovering Pericyte Signaling and Metabolic Triggers
Dr. Chiba is investigating how vascular endothelial growth factor receptor 2 (VEGF-R2) signaling in pericytes contributes to inflammatory and fibrotic responses after kidney injury. VEGF-R2 is well known for its role in endothelial cell biology, but its function in pericytes is less well understood.
“What we are learning is that VEGF-R2 may play a very different role in pericytes compared to endothelial cells, possibly driving pro-fibrotic signaling,” says Dr. Chiba.
In parallel, the project is examining how pericyte metabolism, specifically the oxidation of short-chain fatty acids, may influence their susceptibility to maladaptive transformation.
“These metabolic processes could make pericytes more prone to fibrotic remodeling,” says Dr. Chiba.
The goal is to identify mechanisms that could eventually be targeted to prevent or limit fibrosis following AKI, thereby preserving kidney function in vulnerable pediatric patients. Although current VEGF-R2 inhibitors are not specific to pericytes and would not be appropriate for this indication, the work could inform future strategies for targeted modulation.
Focus on Pediatric Populations and Long-term Kidney Health
AKI is a common complication in hospitalized infants and children, particularly those undergoing surgery or exposed to nephrotoxic medications. While many patients recover short-term kidney function, the risk of long-term kidney dysfunction, including progression to CKD, is a well-established risk. Neonates are especially vulnerable to long-term consequences of AKI due to immature nephron development and limited regenerative capacity in the kidney.
“Better understanding of the transition from AKI to CKD in children is essential to developing preventive strategies tailored to their unique physiology,” says Dr. Chiba.
This research advances that understanding by focusing on cell types and mechanisms that have not been fully characterized in the pediatric context.
Supporting Early-stage Discovery with Future Translational Potential
The Children’s Trust Grantmakers award is a one-year awarded and is intended to catalyze promising early-stage research and provide a platform for securing future funding. Dr. Chiba plans to use the data generated through this project to support larger-scale proposals that will continue to define the molecular events driving fibrosis in pediatric kidney injury.
“This kind of support allows early-career investigators to pursue new ideas and build the foundation for future studies,” says Dr. Chiba.
Earlier in 2025, Dr. Chiba was awarded a George M. O’Brien Kidney Resource Alliance Opportunity Pool Program (OKRA OPP) pilot grant to support his research on understanding how acute kidney injury (AKI) progresses to chronic kidney disease.
Other 2025 Children's Trust Grantmakers Awardees
Two additional projects were selected for funding through the Children’s Trust. First place and $70,000 was awarded to Glenn Rapsinski, MD, PhD, for research into chronic lung infections in ventilator-dependent children. Third place and $30,000 was awarded to Vikram Raghu, MD, MS, for a multicenter study on quality of life in children with intestinal failure.
Further Reading
Below is a selection of prior research published by Dr. Chiba and colleagues.
