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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK080984-04
Application #
8323943
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2009-09-15
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$174,528
Indirect Cost
$12,928
Name
University of California Los Angeles
Department
Pediatrics
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Hanudel, Mark R; Wesseling-Perry, Katherine; Gales, Barbara et al. (2016) Effects of acute kidney injury and chronic hypoxemia on fibroblast growth factor 23 levels in pediatric cardiac surgery patients. Pediatr Nephrol 31:661-9
Pereira, Renata C; Andersen, Thomas L; Friedman, Peter A et al. (2016) Bone Canopies in Pediatric Renal Osteodystrophy. PLoS One 11:e0152871
Pereira, Renata C; Delany, Anne M; Khouzam, Nadine M et al. (2015) Primary osteoblast-like cells from patients with end-stage kidney disease reflect gene expression, proliferation, and mineralization characteristics ex vivo. Kidney Int 87:593-601
Pereira, Renata C; Valta, Helena; Tumber, Navdeep et al. (2015) Altered Osteocyte-Specific Protein Expression in Bone after Childhood Solid Organ Transplantation. PLoS One 10:e0138156
Pereira, Renata C; Jüppner, Harald; Gales, Barbara et al. (2015) Osteocytic protein expression response to doxercalciferol therapy in pediatric dialysis patients. PLoS One 10:e0120856
Carvalho, Catarina G; Pereira, Renata C; Gales, Barbara et al. (2015) Cortical and trabecular bone in pediatric end-stage kidney disease. Pediatr Nephrol 30:497-502
Khouzam, Nadine M; Wesseling-Perry, Katherine; Salusky, Isidro B (2015) The role of bone in CKD-mediated mineral and vascular disease. Pediatr Nephrol 30:1379-88
Bacchetta, Justine; Chun, Rene F; Gales, Barbara et al. (2014) Antibacterial responses by peritoneal macrophages are enhanced following vitamin D supplementation. PLoS One 9:e116530
van Venrooij, Natalie A; Pereira, Renata C; Tintut, Yin et al. (2014) FGF23 protein expression in coronary arteries is associated with impaired kidney function. Nephrol Dial Transplant 29:1525-32

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