Abstract

Chronic kidney disease–mineral and bone disorder (CKD-MBD) is a major complication of chronic kidney disease (CKD), characterized by disruptions in mineral metabolism, abnormal bone turnover and vascular calcification, which collectively increase the risk of fractures and cardiovascular disease. This review examines the molecular mechanisms underlying CKD-MBD, with a particular focus on the fibroblast growth factor 23 (FGF23)–Klotho axis – a key regulator of phosphate balance, vitamin D activation and parathyroid hormone secretion. In CKD, elevated FGF23 levels and reduced Klotho expression contribute to mineral homeostasis disturbances and bone abnormalities. The dysregulation of this pathway plays a central role in CKD-MBD pathophysiology and its associated complications. Emerging therapies, such as anti-FGF23 antibodies and recombinant Klotho, hold promise for modulating FGF23 activity and restoring mineral balance. This review highlights the importance of individualized treatment strategies based on bone turnover patterns and FGF23–Klotho axis dysfunction. Advancing our understanding of these molecular mechanisms will aid in the development of more effective diagnostic tools and therapeutic interventions to improve CKD-MBD outcomes.

Keywords
bone turnover, chronic kidney disease, FGF23, Klotho, mineral and bone disorder

Highlights

What is the topic of this review?

This review explores the molecular mechanisms driving bone turnover dynamics in CKD-MBD, with a primary focus on the FGF23–Klotho axis, a critical regulator of phosphate balance, vitamin D activation and parathyroid hormone secretion.

What advances does it highlight?

The pathophysiology of bone turnover dynamics in CKD-MBD is complex and interrelated, with multiple molecular and cellular determinants involved. This highlights the potential of emerging therapies targeting this multifaceted pathway, including anti-FGF23 antibodies and recombinant Klotho, as well as PTH analogues, activin A receptor inhibitors and anti-sclerostin antibodies.