Pilot 9: Vitamin D metabolism in cystic fibrosis

P.I.: Ian de boer, MD
Associate Professor of Medicine
Nephrology

Bryan Kestenbaum, MD
Associate Professor of Medicine
Nephrology

Vitamin D deficiency is one of the most common nutritional deficits in cystic fibrosis (CF) patients, is resistant to treatment, and may contribute to bone disease and infections. Possible reasons for vitamin D deficiency in CF include intestinal malabsorption, altered liver metabolism, and loss of vital carrier proteins in the urine; however, empiric evidence to support these mechanisms is lacking.

In this project we propose a series of experiments designed to comprehensively define the vitamin D metabolic axis in CF. First, we will characterize the circulating profile of vitamin D metabolites, vitamin D carrier proteins, and downstream hormonal responses in 100 adult CF patients and 50 control subjects. Next we will conduct formal pharmacokinetic studies of radiolabeled tracer to probe the fate of substrate vitamin D in CF patients. We will then measure transcription of key vitamin D metabolism genes in circulating monocytes. Identifying the underlying causes of vitamin D deficiency in CF patients could suggest novel treatments that target vitamin D deficiency as a means to improve clinical outcomes in this disorder.