Texas A&M Department of Nutrition researchers target chronic kidney disease  

Researchers in the Texas A&M College of Agriculture and Life Sciences Department of Nutrition are involved in a new National Institutes of Health-funded study among multiple principal investigators to reduce the future development of kidney disease in preterm infants.

The NIH’s National Institute of Diabetes and Digestive and Kidney Diseases was the awarding agency funding the study, “Investigating the Effect of Dysregulated Vitamin D Metabolism on Kidney Development Following Preterm Birth.”  

Masako Suzuki, DVM, Ph.D., one of the principal investigators for the study, is an assistant professor in the Department of Nutrition. She and her laboratory team at Texas A&M will investigate the role of the vitamin D pathway in the developing kidney as well as the mechanisms connecting vitamin D deficiency to chronic kidney disease in preterm infants.

The department’s new postdoctoral associate, Ayyappa Sista, Ph.D., an expert in bioinformatics, will use multiomics analysis to gain insights into the molecular mechanisms involved.

“For the study, my team will investigate the vitamin D pathway and how this pathway influences kidney development, focusing on a key cell in the kidney known as the podocyte,” Suzuki said. “Our findings should help build the foundation for a clinical trial in preterm babies that will optimize environmental and maternal factors to reduce chronic kidney disease development.”

Study collaborators include Kimberly Reidy, M.D., Albert Einstein College of Medicine, and Jennifer Charlton, M.D., University of Virginia, who will also serve as co-principal investigators, along with Mark Conaway, Ph.D., University of Virginia, and Kevin Bennett, Ph.D., Washington University.

Preterm infants and chronic kidney disease

Vitamin D deficiency is common in preterm infants and has been connected to causing disease in several organs, such as the lung and retina. In the kidney, vitamin D supplementation has been shown to prevent the loss of podocytes in animals with glomerular diseases, which affect the filtering components of the kidney.  

Podocytes are a particularly vulnerable cell type, and podocyte damage or loss is an early factor in many kidney diseases.

“The podocyte is a differentiated cell that is vital to the integrity of the glomerular filtration barrier, and a loss of podocytes often leads to chronic kidney disease,” Suzuki said. “Preterm birth is associated with both increased podocyte loss and these diseases.”

She said while the kidney is known to be a major source of the active form of vitamin D, little is known about either the effect of perinatal vitamin D deficiency on the developing kidney or its association with long-term risk for kidney diseases later in life.

Suzuki’s investigation into vitamin D dysregulation

In their research, Suzuki and her team hope to gain insights into how vitamin D affects podocyte differentiation during preterm development by examining the genome – the complete set of genetic instructions provided by the DNA – as well as the transcriptome – gene expression patterns. To do this, they will employ advanced technologies such as sequencing the kidney at a single-cell level.

Suzuki said she and her team will investigate whether the dysregulation of vitamin D metabolism in the preterm kidney causes a local deficiency of active vitamin D, resulting in impaired podocyte differentiation and deceased podocyte density. They will study both neonate and maternal vitamin D dysregulation to find out.

“We will characterize how the vitamin D pathway contributes to neonatal kidney development by measuring systemic and kidney-based vitamin D metabolites along with key regulators of vitamin D metabolism,” she said. “To determine the independent effect of activated vitamin D pathway on the podocyte, we will treat preterm mice models just after birth with active vitamin D or vitamin D antagonists.”

Suzuki said previous research acted as a springboard for this new project.

Their past research showed the vitamin D pathway was disrupted in preterm mouse models. The researchers also found early birth altered the expression of genes involved in vitamin D metabolism in the kidney, leading to lower podocyte numbers and chronic kidney disease.

“The results suggested a local reduction of active vitamin D in the kidneys, as well as a reduction in podocyte differentiation, which is regulated by vitamin D,” she said.

She said the previous research was key to their further study because the kidney is a major source of vitamin D activation, and activated vitamin D is critical to maintaining healthy podocytes. 

New findings and potential therapies for kidney disease

Suzuki said findings from the new study will allow for a better understanding of how vitamin D affects kidney development and if supplementation of active vitamin D could benefit kidney development in preterm infants.

“Results from this study should help provide the basis for a feasible clinical trial using nutritional modifications in newborns or mothers to improve kidney health outcomes of those born preterm,” she said.  

Suzuki said potential therapeutic options to overcome the vitamin D dysregulation in preterm infants could include vitamin D supplementation or maternal vitamin D administration.

Suzuki and her team, in conjunction with other study collaborators, will also investigate whether supplementation of active vitamin D could improve other organs such as the lung, brain and eye, which also depend on vitamin D for normal development