FGF-23 Regulation in Chronic Kidney Disease

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DESCRIPTION (provided by applicant): Bone disease is prevalent in pediatric patients with chronic kidney disease (CKD) and leads to adverse outcomes such as poor growth, bone pain, and fractures. Furthermore, cardiovascular disease is the leading cause of death in children and adults with CKD while bone and cardiovascular disease appear to be linked in this population. Currently, calcium, phosphorus, PTH, and vitamin D metabolism are used to monitor bone disease and guide its treatment. However, correction of these factors ameliorates, but does not cure, bone and vascular lesions in CKD. A newly described protein, fibroblast growth factor 23 (FGF- 23), has been identified in individuals and animals with normal kidney function who have bone disease and disordered mineral ion homeostasis. High levels of the protein are also found in individuals with CKD and these high levels have been linked to an increased mortality rate. FGF-23 is made in bone and levels rise as CKD progresses; the regulation of FGF-23 in individuals with CKD is, however, unknown. Thus, this study will evaluate: 1) The response of FGF-23 to phosphate binder therapy in CKD stages 2-4 CKD 2) The bone expression of FGF-23 and other factors involved in skeletal mineralization in patients with CKD stages 2-4 These specific aims will be investigated by evaluating changes in FGF-23 to oral phosphate load in a cohort of patients with CKD stages 2-4 who are treated with phosphate binding agents. The relationship between FGF-23 and skeletal mineralization will be assessed by immunohistochemical evaluation of bone in patients with CKD who undergo bone biopsy. PUBLIC HEALTH RELEVANCE: A new protein, FGF-23, may contribute to bone and cardiovascular disease associated with chronic kidney disease (CKD). However, the regulation of FGF-23 in patients with CKD is unknown. This study will examine how FGF-23 is regulated in children and young adults with CKD. An understanding of its pathophysiology may ultimately lead to new treatment algorithisms that decrease morbidity and mortality.