Good things always come in threes, so the saying goes, and the rule certainly held true for three outstanding physician-researchers at CHOP who received 2016 Young Physician-Scientist Awards. As part of this special recognition, they shared their novel insights at a joint meeting of the Association of American Physicians, the American Society for Clinical Investigation, and the American Physician Scientists Association in April.
Gregory E. Tasian, MD, MSc, MSCE
Although kidney stones are more common in adults, the diagnosis of this painful condition in children has risen dramatically over the past 25 years. Despite that fact, little is known about the best treatment course and prevention strategies for children with kidney stones. Gregory E. Tasian, MD, MSc, MSCE, witnessing this trend firsthand as a pediatric urologist and epidemiologist, has developed a research program that seeks to identify determinants of kidney stone disease and effective interventions to reduce the risk of kidney stone recurrence among children.
His findings gained attention for identifying the effect of daily temperatures on kidney stone presentation. In his study, published in Environmental Health Perspectives, Dr. Tasian reported that extremes of hot and cold temperatures were associated with an increased risk of presenting with kidney stones. These results suggest that current and future climate change may contribute to increased morbidity from kidney stones, which currently affects approximately 9 percent of the U.S. population. Specifically, he found that the delay between high daily temperatures and kidney stone presentation was short, peaking within three days of exposure to hot days. Sizzling temps increase evaporative water loss, which leads to a higher concentration of calcium and other minerals in the urine that promote the formation of kidney stones.
“The goal of my research is ultimately to lead to personalized, targeted interventions to increase fluid intake and decrease the risk of recurrence,” said Dr. Tasian, who also is an assistant professor of Surgery and Epidemiology at the Perelman School of Medicine at the University of Pennsylvania. “If we can identify those periods of risk, then we also can identify interventions to offset that risk.”
Read more about Dr. Tasian’s kidney stones research in our blog.
Michelle Denburg, MD, MSCE
Michelle Denburg, MD, MSCE, is an attending physician in the division of Nephrology at CHOP and an assistant professor of Pediatrics and Epidemiology at the Perelman School of Medicine. In addition to both earning Young Physician-Scientist Awards, Dr. Tasian and Dr. Denburg have something else in common: Their research interests overlap in fascinating ways.
Kidney stones are increasingly being recognized as a chronic disorder of mineral metabolism, which is a focus of Dr. Denburg’s research on bone health in childhood chronic kidney disease. Dr. Denburg and Dr. Tasian worked together on a research paper published in the Clinical Journal of the American Society of Nephrology that showed people with kidney stones — especially male teens and young women — are at a higher risk for bone fractures than the general population.
“Recognizing that these children are at high risk for compromised bone health, the next step is identifying factors that we can modify to optimize their bone accrual as much as we can and set them up for entering adulthood in a better state,” Dr. Denburg said.
At the joint meeting of the young investigators in Chicago, Dr. Denburg presented a related study published in Kidney International that evaluated the impact of interventions for kidney stones on the development of hypertension and chronic kidney disease. This study confirmed that patients with kidney stones are at higher risk for developing hypertension and chronic kidney disease, and found that shock wave lithotripsy to the kidney is independently associated with a significantly higher risk of hypertension, while ureteroscopy is not. Therefore, this study has important implications for the management and long-term follow-up of these patients.
Dr. Denburg’s research program is also focused on bone and mineral metabolism in patients with another form of kidney disease, nephrotic syndrome. A new project that Dr. Denburg is excited to launch is her collaboration with PEDSnet and the NephCure Kidney Network to create a Pediatric Glomerular Disease Learning Network (GLEAN) along with pediatric nephrologists from eight participating institutions, including CHOP. Patients with glomerular diseases lose protein in their urine. When these protein losses are very high, called nephrotic syndrome, patients experience swelling, low blood protein, and potentially deterioration of kidney function and other complications.
GLEAN investigators are using data captured in the electronic health record to identify patients with glomerular disease across the eight pediatric centers and create a large cohort of participants to enable outcomes and comparative effectiveness research, quality improvement studies, and eventually pragmatic clinical trials. One of the initial goals Dr. Denburg aims to accomplish through GLEAN is to perform the first study of musculoskeletal outcomes in children and adolescents with glomerular diseases.
“Since PedsNet has more than 5 million children represented, GLEAN is an opportunity to study patients with these rare diseases on a much larger scale than in the past and to address many of the challenges to implementing high quality trials,” Dr. Denburg said.
Shana McCormack, MD, MTR
Shana McCormack, MD, MTR, an attending physician in the division of Endocrinology and Diabetes at CHOP who studies neuroendocrine regulation of energy balance, was proud to be in the company of her fellow colleagues who were honored with Young-Physician Scientist Awards. Dr. McCormack is especially interested in finding potential common pathways of mitochondrial dysfunction in patients with diabetes and patients with genetic mitochondrial disorders.
Dr. McCormack received great feedback at the joint meeting that gathered all the young investigators when she presented her project that uses novel magnetic resonance imaging (MRI) studies of muscle mitochondrial function. The new noninvasive technique, developed by her colleagues at the University of Pennsylvania’s Center for Magnetic Resonance and Optical Imaging, estimates mitochondrial energy production.
More precisely, this technique can detect changes in muscle creatine content before and after exercise that allow estimation of mitochondrial oxidative phosphorylation (OXPHOS) capacity, an important indicator of energy production. Some of the advantages of this new approach, called creatine chemical exchange saturation transfer (CrCEST), are that it is noninvasive, avoiding the need for a muscle biopsy, and that it provides excellent anatomic resolution, allowing researchers to assess mitochondrial function in different muscle groups simultaneously.
“The mitochondria are the energy-producing factories of the cell, and there are a number of endocrine conditions that are characterized by decreased oxidative phosphorylation capacity, where the mitochondria are not producing energy properly,” Dr. McCormack said. “This problem has all sorts of downstream effects, and different muscle types can be affected differently in response to metabolic diseases. In order to study the phenomenon better, we need to have a good, noninvasive way of measuring mitochondrial oxidative phosphorylation capacity, especially if we wish to study children longitudinally to assess the impact of a metabolic disease.”
In a paper published in the November issue of JCI Insight, Dr. McCormack and her colleagues demonstrated that CrCREST is a viable technique to measure OXPHOS capacity in individuals with genetic mitochondrial diseases. This new tool will help researchers to gain insights into mitochondrial bioenergetics and provide an objective biomarker for clinical treatment trials so that they can determine if an intervention is helping a patient’s mitochondria to function better.
Dr. McCormack is also an assistant professor of Pediatrics at Penn. Read more about her research on disorders of energy balance in our blog.