Research Spotlight: Improving Kidney Health in Preterm Infants
Jennifer Charlton, MD, is a pediatric nephrologist at UVA Health Children's, where she researches how adverse maternal environments and preterm birth can impact long-term kidney health. With new, targeted therapies, she hopes to improve the lives of these infants and reduce their risk of chronic kidney disease.
As part of the Neonatal Kidney Collaborative, Charlton participates in collaborative research and advocacy.
Read more of her published research.
Improving Kidney Health in Preterm Babies
I love that I have the privilege and the pleasure of working with a large diverse group of researchers. I love that I have the opportunity to work with trainees, to teach them about our research and engage them in research. And I love that I have the opportunity to share that research with our patients and our families.
My name is Jennifer Charlton. I'm an associate professor in the Department of Pediatrics. And I am a pediatric nephrologist, which means that I take care of kids that have kidney problems. My lab focuses on adverse maternal environments and how they can impact long-term kidney health, particularly for those who are born preterm or born early. I also collaborate with biomedical engineers from Washington University to develop non-invasive ways of measuring nephron number.
So chronic kidney disease affects one in seven adult Americans, and in its most simple definition, chronic kidney disease is too few nephrons to do the work of the kidney. What most people don’t understand is that all of your nephrons in a human are made at the time you're born full-term. If you are born preterm, the risk of chronic kidney disease is much greater, and that is because of the life-saving therapies that these babies undergo at a very early and vulnerable period.
My future hope is that our research will impact the lives of these preterm neonates by developing targeted therapies to reduce their risk for chronic kidney disease over their lifetime.
What are you working on right now?
The main focus of our lab is to understand how adverse maternal environments lead to chronic kidney disease. Chronic kidney disease at its most simple definition is too few nephrons (filtering units) to do the work of the kidney. We use two animal models, including a model of preterm birth and model of growth restriction to mimic these adverse maternal environments.
Over the last decade, we have collaborated with biomedical engineers to develop strategies to noninvasively measure nephron number in these animal models. In the preterm mouse model, we recently discovered alterations in the vitamin D pathway just after birth. That led to a proposal to the NIH that was funded in 2024 to evaluate the vitamin D pathway in this unique mouse model. Our focus in the lab is to better understand the vitamin D pathway in the developing mouse kidney and also use patient samples to see if the alterations of the vitamin D pathway are present in our preterm neonates.
What are the most intriguing potential clinical applications of your work?
The alterations in the vitamin D pathway may provide a unique repurposing of a drug that is already FDA approved for other indications. If the vitamin alterations are also present in preterm neonates, we may be able to give them an active form of vitamin D to help improve both kidney development and the development of other organs.
Our work on noninvasive methods to enumerate nephron number is also very clinically exciting. Currently, we use a contrast to highlight each nephron in our animal models, but we are working on ways to reduce or eliminate the contrast, developing an imaging modality to quantify nephron number that can be safe and easy.
What recent paper has impacted the way you think?
The paper that has really impacted my work was Prevalence and Risk Factors for Kidney Disease and Elevated BP in 2-Year-Old Children Born Extremely Premature. This study was an ancillary study of a randomized control trial using Epogen to improve neurocognitive outcomes, and in this ancillary study, they looked at the kidney outcomes of this preterm population.
They found ~18% had CKD at the age of 2 years, and a large percentage had protein in their urine or elevated blood pressure. This is the first study to really show how big of an impact preterm birth has on kidney health. I now have objective data to show what a large problem this is and we can use this to power future studies. To date, there has never been a clinical trial focused on improving kidney outcomes in those born preterm.
What made you choose UVA Health as the place to do your research?
I did my pediatric nephrology fellowship here. I found amazing support to launch a career as a physician scientist.
What do you wish more people knew about your area of research?
In humans, all nephrons are formed by the time of full-term birth. If a baby is born early or does not have a great environment, kidney development will be sacrificed. In the US today, 1 in 7 American adults has chronic kidney disease.
I believe much of the origin of this classically adult disease starts in the fetus. In our preterm population of neonates, we have a responsibility to make that environment as good as we can to help all organs grow normally. We need further research into how to do that best for kidney development. It is important to remember that kidney injury and longer term chronic kidney disease can impact the health of other organs and influence research studies. Therefore, we should be accounting for kidney health in other studies as a confounder or modifier.
Lastly, I want pediatricians and other healthcare providers to know that babies born preterm have a significant risk for kidney disease, and they should be screened for high blood pressure, counseled not to use over-the-counter medications such as NSAIDs, and encouraged to have a healthy diet including fruits and vegetables. There are now published recommendations on how to follow up vulnerable neonates.
How did you become interested in your area of research?
During fellowship, my mentors showed me how much we didn’t know about kidney development or nephron number. I was really fortunate to attend two NIH sponsored conferences on neonatal acute kidney injury and glomerulo morphometrics that helped me define the space where I wanted to work. In addition, my two children were born mildly preterm. We were blessed that they were only a few weeks early, but the personal experience was a driver in my decision of where to focus my research effort.
