Riley Children’s at the Forefront of Using Reverse Translational Approaches to Study Neonatal AKI
Pediatric nephrologists at Riley Children’s Health are developing a novel reverse translational research program to study the clinical effects and long-term outcomes of acute kidney injury (AKI) in neonates. Reversing the traditional bench to bedside approach, the program, established by Riley nephrologists and researchers Michelle Starr, MD, Kathleen Altemose, MD and Danielle Soranno, MD, is based on the development of pre-clinical animal models that match pathology observed at the bedside in infants with AKI. The pre-clinical models are then studied with the hope of identifying mechanisms or outcomes that can be taken back to the bedside to inform treatment or prompt longer-term clinical investigations, rounding out the bench-to-bedside-back-to-bench approach.
The Neonatal Kidney Health Program integrates robust research to analyze neonatal AKI, largely increasing AKI recognition in the NICU
While reverse translational research is not new, Riley Children’s is at the forefront of using the research approach to investigate neonatal AKI. The research complements the robust multidisciplinary clinical program at Riley Children’s run by Allyson Brock, NP, and Kathryn Lowe, NP, which follows patients from their inpatient care in the NICU through longitudinal follow-up in the Neonatal Kidney Health Program. By using standardized care guidelines and automated trigger alerts within the electronic health record to detect AKI, the novel Neonatal Kidney Health Program at Riley Children’s has increased the recognition of AKI in the NICU from 17% to 100%.
“In neonatal AKI, Riley is unique in that we have the full spectrum of bench to bedside research to complement our clinical program,” said Dr. Starr, who, along with Riley neonatologist Paulomi Chaudhry, MD and nephrology nurse practitioner Allyson Brock, NP, authored a published study highlighting the strategies used to identify AKI in the NICU at Riley Children’s. “So not only do we have clinical deployment of a novel inpatient and outpatient program, we also have basic science, translational and health outcomes research to support this program.”
In 2018, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) highlighted the reverse translational approach as a best practice for research and discovery related to AKI
“While this type of research program is more difficult to set up, it’s more translatable because the animal model is a specific match of what we’re seeing at the bedside,” said Dr. Soranno, a pediatric nephrologist and basic science researcher with expertise in biomedical engineering. “When we study the models, and they present with certain conditions, our clinicians take that information back to the bedside to determine if they’re seeing the same things in our patients; it turns into a cyclical research and discovery process that enables us to study short- and long-term outcomes of AKI.”
With four physician-scientists devoting 75% of their time to research, the nephrology program at Riley Children’s is expanding its scope and influence in pediatric nephrology research. Current areas of collaborative research include the interaction between kidney and lung disease and the role of maternal malnutrition on kidney outcomes in offspring.
“Every physician-scientist in the division is either leading a clinical trial or has National Institutes of Health funding to conduct laboratory-based research,” noted David Hains, MD, nephrology division chief at Riley Children’s.
In the field of neonatal AKI, Drs. Starr and Soranno are active collaborators in major multicenter efforts, including the recent Pediatric Acute Disease Quality Initiative (pADQI) which resulted in a landmark consensus statement
published in JAMA Open. The consensus statement presents the current state of AKI in children and makes recommendations for priorities in research, clinical practice, education and advocacy.