Expanding on her findings about racial differences in pediatric chronic kidney disease-mineral and bone disorder (CKD-MBD), Marciana L. Laster, MD, is using a K23* award from the National Institutes of Health (NIH) and high-value resources at Riley Children’s Health to study the disorder in children, specifically the cardiovascular disease associated with CKD-MBD.
The goal of her research is to identify targeted treatment protocols rooted in precision medicine that address the bone disease while minimizing cardiovascular side effects.
“The risk of cardiovascular death is 1,000-fold higher in kids with CKD-MBD than the general pediatric population,” said Dr. Laster, a pediatric nephrologist and researcher at Riley Children’s. “It’s the number one cause of death for children with the disorder, with Black children appearing to be at increased risk.”
A published study led by Dr. Laster comparing racial and ethnic differences of children with CKD-MBD and on dialysis showed that cardiovascular mortality was about 60% higher for Black children. A second study published in the Journal of Bone and Mineral Research evaluated the impact of race and ethnicity on bone markers—specifically vitamin D and parathyroid hormone (PTH)—and fractures among kids with CKD.
“The trend we saw is that Black children had lower 25-hydroxy D levels and higher PTH, which in CKD can become overactive, yet Black children tended to fracture less than white children,” Dr. Laster said. “It’s a paradox that’s still being studied, but there appears to be some level of PTH resistance in Black patients.”
In addition to vitamin D and calcium supplements, a synthetic calcitriol to reduce PTH levels is commonly used to treat CKD-MBD. The racial differences revealed through the studies, as well as any variants or polymorphisms that exist related to vitamin D, underscore the need, Dr. Laster said, to determine through ongoing research how best to tailor treatment for each individual.
“If we ignore the fact that these differences are there, we run the risk of overtreating some patients and worsening their cardiovascular outcomes,” she said.
One of the few pediatric bone researchers in the nation, Dr. Laster is focused on identifying genetic markers that determine how CKD-MBD manifests. In her research, she uses retrospective data from observational studies, including the NIH-funded CKiD (Chronic Kidney Disease in Children) study and pediatric bone biopsies. At Indiana University School of Medicine, she partners with the Indiana Center for Musculoskeletal Health on alternative ways to evaluate bone without biopsy. The center is one of the few facilities in the U.S. with a high-resolution peripheral quantitative CT (HR-pQCT)—a scanner that produces 3D images with acute sensitivity for changes and abnormalities in bone.
“This scanner enables us to obtain measurements of the bone—it’s not as precise as bone biopsy, but my hope is to prospectively enroll patients in clinical studies to better understand what we can learn,” Dr. Laster said. “Using this tool to monitor bone health, we can determine if medication changes are warranted, or if we need to do anything to alter a patient’s treatment trajectory.”
Adding to her research involving racial differences in pediatric CKD, Dr. Laster plans to use data from the Regenstrief Institute, an IU School of Medicine partner, to evaluate the impact of social determinants of health on patients with chronic kidney disease.
“There are excellent data and resources available through the institute to help us better understand the barriers our patients face in following through on our recommendations, particularly in regard to diet, and to use this data to develop appropriate interventions.”
With the NIH K23 award funding extending through March 2025, Dr. Laster is preparing to submit an R01 proposal to the NIH within the next year.
Nephrology at Riley Children’s Health
The pediatric nephrologists at Riley Children’s are leaders in using novel technologies and research breakthroughs to launch new clinical programs that lead to better treatments for children impacted by kidney disease. Our nephrology specialists provide comprehensive evaluation and treatment for children with kidney disease or kidney failure.
* National Institutes of Health Mentored Patient-Oriented Research Career Development Award (K23)