New study findings that characterize bone expression of various proteins across stages of chronic kidney disease (CKD) could improve understanding of the pathogenesis of CKD mineral bone disease (MBD).
In a study comparing bone expression of proteins in patients with CKD stages 2–5 and healthy patients, a team led by Rosa M.A. Moysés, MD, PhD, of the University of Sao Pãulo School of Medicine in Brazil, found that bone expression of sclerostin and parathyroid hormone receptor-1 increased in earlier stages of CKD, whereas fibroblast growth factor-23 (FGF-23) and phosphorylated b-catenin showed increased expression in later stages of CKD, according to a paper published online ahead of print in Kidney International. Sclerostin is a negative regulator of bone formation by inhibiting Wnt pathway. Therefore, their findings suggest that Wnt pathway inhibition is an early event in the pathogenesis of CKD-MBD, which could explain, at least partially, the bone resistance to PTH usually found in CKD.
The investigators observed a gradual increase in bone resorption associated with a decrease in bone formation and impairment in bone mineralization. As serum calcium decreased, serum phosphate, alkaline phosphatase, FGF-23, parathyroid hormone, and osteoprotegerin increased as CKD progressed, Dr Moysés and her colleagues reported.
Immunohistochemical studies demonstrated that FGF-23 and sclerostin did not co-localize, “suggesting that distinct osteocytes produce these proteins,” Dr Moysés team stated. In addition, the study found a good correlation between serum levels and bone expression of FGF-23.
“The better we understand what is happening inside the bones, the better we will recognize and adequately treat patients with CKD-MBD,” the investigators concluded. “Moreover, the best scenario would be to establish a perfect link between serum biomarkers and bone expression of a specific protein, and then a serum biomarker would tell us precisely what is going on inside the bones.”
The researchers said their results are novel and “might propose new promising methodology to help understand the complicated mechanism of CKD-MBD.” They acknowledged that the study’s non-prospective design and small sample size for immunohistochemistry and quantification of bone proteins were study limitations.
1. Graciolli FG, Neves KR, Barreto F, et al. The complexity of chronic kidney disease-mineral and bone disorder across stages of chronic kidney disease. Kidney Int. 2017; published online ahead of print. doi: 10.1016/j.kint.2016.12.029