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Parathyroid function in chronic kidney disease: role of FGF23-Klotho axis.
Contrib Nephrol. 2013; 180:110-23.CN

Abstract

The parathyroid gland plays a central role in the regulation of mineral metabolism. In patients with chronic kidney disease (CKD), circulating levels of parathyroid hormone (PTH) are progressively increased as kidney function declines, as a result of phosphate retention, hypocalcemia, decreased production of 1,25-dihydroxyvitamin D [1,25(OH)2D], endogenous changes within the parathyroid gland, and skeletal resistance to the actions of PTH. In addition, the identification of fibroblast growth factor 23 (FGF23) and its cofactor Klotho offers important implications for the deeper understanding of disordered mineral metabolism in CKD. In early CKD, increased FGF23 to maintain neutral phosphate balance results in suppression of renal 1,25(OH)2D production and thereby triggers the early development of secondary hyperparathyroidism. FGF23 also acts directly on the parathyroid to decrease PTH synthesis and secretion, but this effect is blunted in advanced stages of CKD, due to decreased expression of the Klotho-FGF receptor 1 complex and increased concentrations of C-terminal FGF23 that competes with full-length FGF23 for binding to the receptor complex. Recent clinical studies also reported that high levels of FGF23 are associated with morbidity and mortality as well as treatment resistance to active vitamin D, suggesting the potential of FGF23 as a novel biomarker to guide treatment of disordered phosphate metabolism in CKD. This review will discuss the pathogenesis of secondary hyperparathyroidism, particularly focusing on the emerging role of the FGF23-Klotho axis in patients with CKD.

Authors+Show Affiliations

Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

23652554

Citation

Koizumi, Masahiro, et al. "Parathyroid Function in Chronic Kidney Disease: Role of FGF23-Klotho Axis." Contributions to Nephrology, vol. 180, 2013, pp. 110-23.
Koizumi M, Komaba H, Fukagawa M. Parathyroid function in chronic kidney disease: role of FGF23-Klotho axis. Contrib Nephrol. 2013;180:110-23.
Koizumi, M., Komaba, H., & Fukagawa, M. (2013). Parathyroid function in chronic kidney disease: role of FGF23-Klotho axis. Contributions to Nephrology, 180, 110-23. https://doi.org/10.1159/000346791
Koizumi M, Komaba H, Fukagawa M. Parathyroid Function in Chronic Kidney Disease: Role of FGF23-Klotho Axis. Contrib Nephrol. 2013;180:110-23. PubMed PMID: 23652554.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Parathyroid function in chronic kidney disease: role of FGF23-Klotho axis. AU - Koizumi,Masahiro, AU - Komaba,Hirotaka, AU - Fukagawa,Masafumi, Y1 - 2013/05/03/ PY - 2013/5/9/entrez PY - 2013/5/9/pubmed PY - 2014/1/22/medline SP - 110 EP - 23 JF - Contributions to nephrology JO - Contrib Nephrol VL - 180 N2 - The parathyroid gland plays a central role in the regulation of mineral metabolism. In patients with chronic kidney disease (CKD), circulating levels of parathyroid hormone (PTH) are progressively increased as kidney function declines, as a result of phosphate retention, hypocalcemia, decreased production of 1,25-dihydroxyvitamin D [1,25(OH)2D], endogenous changes within the parathyroid gland, and skeletal resistance to the actions of PTH. In addition, the identification of fibroblast growth factor 23 (FGF23) and its cofactor Klotho offers important implications for the deeper understanding of disordered mineral metabolism in CKD. In early CKD, increased FGF23 to maintain neutral phosphate balance results in suppression of renal 1,25(OH)2D production and thereby triggers the early development of secondary hyperparathyroidism. FGF23 also acts directly on the parathyroid to decrease PTH synthesis and secretion, but this effect is blunted in advanced stages of CKD, due to decreased expression of the Klotho-FGF receptor 1 complex and increased concentrations of C-terminal FGF23 that competes with full-length FGF23 for binding to the receptor complex. Recent clinical studies also reported that high levels of FGF23 are associated with morbidity and mortality as well as treatment resistance to active vitamin D, suggesting the potential of FGF23 as a novel biomarker to guide treatment of disordered phosphate metabolism in CKD. This review will discuss the pathogenesis of secondary hyperparathyroidism, particularly focusing on the emerging role of the FGF23-Klotho axis in patients with CKD. SN - 1662-2782 UR - https://www.unboundmedicine.com/medline/citation/23652554/Parathyroid_function_in_chronic_kidney_disease:_role_of_FGF23_Klotho_axis_ L2 - https://www.karger.com?DOI=10.1159/000346791 DB - PRIME DP - Unbound Medicine ER -