UPMC Children’s Pediatric Nephrology Team Creates New Model System to Study AKI to CKD Progression

Takuto Chiba, PhD, research assistant professor, Division of Pediatric Nephrology at UPMC Children’s Hospital of Pittsburgh, is senior author on a recently published study, “Mouse Model of Acute to Chronic Kidney Disease Transition Induced by Renal Ischemia/Reperfusion Injury,” published in the Journal of Visualized Experiments. Akira Oda, MD, PhD, visiting scholar, was the first author of the study.

Dr. Chiba’s laboratory focuses on the mechanisms that drive long-term damage following acute kidney injury (AKI), including fibrosis and microvascular dysfunction. His research has examined how cellular processes, including pericyte transformation and metabolic dysregulation, contribute to progression from AKI to chronic kidney disease (CKD).

The Challenge in Studying AKI to CKD Progression

AKI is common in hospitalized and critically ill patients. While many patients recover, a subset experience incomplete recovery and are at higher risk for developing CKD. Individuals who experience AKI also are at increased risk for a future AKI. Clinically, there are limited tools to predict which patients will progress over time from AKI to CKD, and there are still no approved therapeutics to halt or repair damage to kidney tissues once AKI has occurred.

One of the challenges for basic science researchers like Dr. Chiba and colleagues studying kidney injury has been how to study the progression from AKI to CKD in a way that captures both phases of the disease in a single model system.

“Modelling the entire process from AKI to CKD has been difficult to study experimentally because most models capture either the initial injury or the chronic outcome, not both over time,” Dr. Chiba says. “To try and overcome that limitation, we designed a new model system designed to better look at how progression happens over time, but is also flexible in how we can study potential interventions.”

How the New Model Works

The new model system created by Dr. Chiba and colleagues employs a unilateral ischemia-reperfusion injury approach to precipitate AKI in one kidney. The second kidney remains in place during the acute injury phase and is removed later, just prior to analysis.

This sequencing allows the model to progress through the acute phase while preserving survival. It also allows the team to measure kidney function during the chronic phase. Existing models that allow functional assessment often limit long-term study, while models that allow survival do not support functional measurement. This approach allows both.

Over time, the injured kidney develops sustained functional impairment along with interstitial fibrosis and gene expression changes associated with chronic kidney disease. Because function and structure can be assessed in the same model, Dr. Chiba and colleagues can examine how early injury leads to later fibrosis and persistent decline.

“This new model provides a controlled way to study the transition from AKI to CKD,” Dr. Chiba says. “It will allow investigations of the mechanisms that drive progression and create a setting in which potential interventions can be evaluated in relation to long-term outcomes.”

Connection to the PCEN Initiative

The Pediatric Center of Excellence in Nephrology (PCEN) initiative at UPMC Children’s Hospital of Pittsburgh is a multidisciplinary effort to build the research infrastructure needed to study kidney injury and disease progression and compete for a National Institutes of Health P50 grant to become a NIH-designated Pediatric Center of Excellence in Nephrology.

Within the initiative, Dr. Chiba serves as co-director of the Model Systems Core, which develops and supports preclinical kidney injury models used across collaborative studies.

This model contributes to that effort by providing a standardized platform for studying progression from acute kidney injury to chronic disease.

Study Reference

Oda A, Malta Cerqueira D, Kinoshita A, Ho J, Sims-Lucas S, Chiba T. Mouse Model of Acute to Chronic Kidney Disease Transition Induced by Renal Ischemia/Reperfusion Injury. J Vis Exp. 2026; (228):e69866.

Further Reading

Read more about the PCEN initiative at UPMC Children’s on UPMCPhysicianResources.com.