Medical Professional Publications

Why Do Some Children Have Kidney Scarring After Infection?

Columbus, OH — March 2017

After a febrile urinary tract infection (UTI), up to 20 percent of toddlers and preschool-age children can experience kidney scarring. At present, there are no strategies to predict which patients are at risk for kidney scarring or to limit the extent of scarring.

Brian Becknell, MD, PhD, a pediatric nephrologist at Nationwide Children’s Hospital and principal investigator in the Center for Clinical and Transitional Research at The Research Institute at Nationwide Children’s, recently led a team that developed a new mouse model of kidney scarring following UTI. Their results were published in the American Journal of Physiology: Renal Physiology.

Limited understanding of the pathophysiology, immune cell recruitment and gene expression changes that occur during a UTI have prevented the development of therapies to prevent recurrent infection and scarring.

Dr. Becknell and colleagues addressed this issue using a mouse model with vesicoureteral reflux (VUR), a risk factor for kidney scarring in human patients. The researchers found their mouse model mirrored the major pathological features observed in children with kidney scarring following UTI.

“It is an easy model in which to initiate a UTI and then look at the role of inflammatory cells of the immune system in the process of kidney scarring,” says Dr. Becknell, who is also an assistant professor of Pediatrics at The Ohio State University College of Medicine. “We can do things like ultrasound to image the kidneys just as we would for a child with a UTI, and we’re able to determine the relationship between the infection, the immune response and the scarring.”

Previous animal models relied on immune-deficient mice, but this new model uses mice without any defects in their immune systems. That’s important because most children who experience UTIs and kidney scarring have otherwise normal immune systems.

Dr. Becknell and his colleagues see several potential uses for their mouse model.

“Researchers can use this model as a platform to develop and test novel medications and interventions aimed at reducing kidney scarring after UTI,” he says. “They can also use it to understand, at a mechanistic level, the contribution of specific immune cells to kidney scarring.”

Additionally, the model may allow researchers to better understand genetic risk factors for kidney scarring, so they can predict which children are most at risk.

Dr. Becknell says it may be years until the model can be extrapolated to children in the clinic. However, this mouse model provides a framework to investigate the molecular processes that distinguish infections that lead to kidney scars from those that eventually resolve.

“I am optimistic that at the very least we can use this model as a means to identify potential strategies to prevent kidney scarring in children and ideally use it as a pre-clinical platform to test interventions and move toward clinical use eventually,” says Dr. Becknell.

The hope is that this new mouse model will serve as a tool to dissect the mechanisms contributing to kidney scarring. A better understanding of the factors that contribute to kidney scarring following UTIs will lead to innovative approaches to quell infection, prevent chronic kidney disease, and preserve kidney function.

Li, B, Haridas, B, Jackson, A R, Cortado, H, Mayne, N, Kohnken, R, Bolon, B, McHugh, K M, Schwaderer, A L, Spencer, J D, Ching, C B, Hains, D S, Justice, S S, Partida-Sanchez, S, and Becknell, B. Inflammation drives renal scarring in experimental pyelonephritis. American Journal of Physiology: Renal Physiology. 2017 Jan 1; 312(1): F43-F53.

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