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Building the Foundation for a Pediatric Center of Excellence in Nephrology

July 29, 2025

9 Minutes

A multidisciplinary team at UPMC Children’s Hospital of Pittsburgh, led by Division of Pediatric Nephrology chief Jacqueline Ho, MD, MS, and research director of Pediatric Nephrology, Sunder Sims-Lucas, PhD, were awarded a Snyder Family Foundation FIRST grant through the Children’s Hospital of Pittsburgh Foundation to establish the scientific groundwork and evidence for a future National Institutes of Health (NIH)-designated Pediatric Center of Excellence in Nephrology (PCEN). The project supported by the FIRST grant is focused on neonatal acute kidney injury (AKI) and the development of new research tools, preclinical models, clinical data, and training resources in preparation for a 2027 NIH P50 PCEN application.

Funding Through Philanthropy

The Snyder Family Research Fund was established by UPMC Children’s Hospital Foundation and UPMC Children’s Trustee Mark Snyder and his wife, Carolyn, with additional support from other members of the Snyder family. The fund provides scientific leaders with flexible resources to advance early-stage research initiatives and accelerate discovery. The current nephrology FIRST grant, awarded in the second year of the program, is designed to catalyze the formation of interdisciplinary teams pursuing ambitious translational goals.

"The vision behind the FIRST program is to support research teams in forming the kind of infrastructure and preliminary data that can make them competitive for larger NIH funding mechanisms like a P50," says Dr. Ho.

A Better Understanding of Neonatal AKI Risks and Outcomes

The initiative centers on the clinical and biologic complexity of neonatal AKI, a condition that affects approximately 30% to 40% of preterm infants in the NICU and significantly elevates their lifetime risk for chronic kidney disease (CKD).

"This is a population at high risk because they are born with incomplete kidney development and are then exposed to a high-stress environment in the NICU," says Dr. Ho. "We're trying to understand which patients are most at risk and what mechanisms contribute to long-term injury."

Kidney development begins at approximately five weeks of gestation and continues through the 34th to 36th week. Preterm infants, particularly those born before 30 weeks, may not complete nephrogenesis, leaving them with a reduced number of nephrons. This nephron deficit, compounded by common complications of prematurity such as infection or systemic inflammation, makes the developing kidney particularly susceptible to injury.

The FIRST-funded effort is organized around three interrelated research projects that examine susceptibility, detection, and therapeutic modulation of neonatal AKI.

The first of these, led by Dana Fuhrman, DO, MS, associate professor of critical care medicine and pediatrics at the University of Pittsburgh School of Medicine, is a prospective clinical study focused on identifying early urinary biomarkers in preterm infants. Dr. Fuhrman brings to the effort extensive prior research into kidney frailty and biomarker development in other high-risk pediatric populations, including children undergoing cardiac surgery. For this study, she is applying her expertise to a new patient population: neonates in the NICU.

The project is being carried out in collaboration with Megan Gates, MD, MS, a combined neonatal-perinatal medicine and pediatric nephrology fellow at UPMC Children’s. Dr. Gates is leading the day-to-day work of the study as her fellowship research project, with mentorship from Dr. Fuhrman.

"Dr. Gates is ideally positioned to take on this project," says Dr. Ho. "Her training spans both neonatal medicine and nephrology, and she is focused on investigating how urinary biomarkers, particularly dicarboxylic acids, might identify which neonates are most vulnerable to developing AKI."

The second project, led by Dr. Ho, is focused on evaluating how prenatal stressors such as maternal diabetes and malnutrition affect kidney development and AKI susceptibility in the postnatal period. The study uses murine models to examine both structural and functional changes in the kidney, with particular attention to nephron number and glomerular filtration rate measured by FITC-sinistrin clearance. The study also includes biomarker analyses of urinary dicarboxylic acids to evaluate their potential as early predictors of kidney injury.

"There is a clear link between prenatal exposures and long-term kidney risk, but we have limited tools to study how these early insults shape vulnerability," says Dr. Ho. "Our goal is to build sensitive, translationally relevant models that can support future therapeutic studies."

The third project is jointly led by Dr. Sims-Lucas, PhD, and Neil Hukriede, PhD, professor in the Department of Cell Biology and director of the Center for Integrative Organ Systems at the University of Pittsburgh. Their work focuses on using human induced pluripotent stem cell (iPSC)-derived kidney organoids to model neonatal AKI and test potential therapeutic interventions.

One of the advantages of the kidney organoid platform developed by Dr. Hukriede’s laboratory is its developmental stage.

"Kidney organoids for modeling diseases or testing therapeutics can sometimes be problematic or criticized for not being fully mature. However, in our case, that immaturity is exactly what makes them useful," says Dr. Ho. "They closely resemble a preterm kidney, which makes them ideal for modeling neonatal kidney injury."

Drs. Sims-Lucas and Hukriede are using the platform to test the protective effects of dicarboxylic acids, a class of molecules that have shown benefit in adult AKI models but have not been evaluated in neonatal systems. The team is also investigating post-translational modifications such as succinylation that may mediate cellular injury and repair.

Cores to Support National Collaboration and Sustainability

To ensure scalability and continuity, the Pitt-PCEN team is also developing three support cores designed to serve both local and national research needs.

The Model Systems Core, co-directed by Dr. Hukriede and Takuto Chiba, PhD, research assistant professor of pediatrics, will provide access to validated small animal AKI models and the kidney organoid platform. It also offers training and consultation for investigators developing new experimental approaches.

The Biospecimen Core, led by Dr. Fuhrman and Dr. Hukriede, is building a centralized biorepository for clinical and experimental samples, including human urine and blood, animal tissue, and organoids. The core will also manage a cloud-based data interface to support sample access and collaborative use.

The Education Core, directed by Dr. Ho and Dr. Sims-Lucas, is focused on workforce development in pediatric kidney research. Its activities include producing multimedia didactic materials, developing a research curriculum, hosting an annual research symposium, and coordinating mentorship opportunities for trainees at multiple stages of career development.

"One of the persistent challenges in pediatric nephrology is the shrinking pipeline of physician-scientists," says Dr. Ho. "Through the Education Core, we are creating resources that can help early-career researchers gain skills, visibility, and mentorship at a critical juncture."

A Strategic Platform for Sustained Progress in Kidney Research and Clinical Advancement

While the near-term objective is to submit a competitive NIH P50 PCEN application in 2027, Dr. Ho explains that the current work is designed to deliver meaningful scientific and clinical value regardless of that outcome.

"The philanthropic support from the Snyder Family Research Fund enables us to pursue high-priority questions and build a platform for collaborative research," says Dr. Ho. "Even beyond the P50 application, this work will inform our understanding of neonatal kidney disease and shape future interventions."

As a model for institutionally supported translational research, the FIRST program has enabled the Division of Pediatric Nephrology at UPMC Children’s to assemble an integrated and multidisciplinary team of investigators with complementary expertise that spans molecular biology, critical care medicine, neonatology, regenerative medicine, and cutting-edge basic science. The Pitt-PCEN initiative is an important effort in addressing an understudied and high-risk population in pediatric kidney care.

Reading References

Below is a selection of published research from the team members for further reading.

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