| Theme |
Recent advances in research concerning FGF23 and Klotho |
| Title |
Role of FGF23-Klotho axis in CKD-MBD |
| Author |
Masahiro Koizumi |
Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine |
| Author |
Masafumi Fukagawa |
Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine |
| [ Summary ] |
The identification of FGF23 and Klotho as its cofactor has transformed the classic view of endocrine regulation of phosphate homeostasis and pathogenic mechanisms related to CKD-MBD. Individuals with CKD experience decreased Klotho expression as early as stage 1 CKD. Klotho continues to decline as CKD progresses, causing FGF23 resistance and provoking large FGF23 and parathyroid hormone increases, as well as hypovitaminosis D. The Klotho protein not only serves as a cofactor for FGF23, but also functions as a humoral factor. Klotho's extracellular domain is released into the blood and urine by ectodomain shedding and exerts various functions independently of FGF23, including regulation of multiple ion channels and transporters. Decreased urinary Klotho protein levels have been identified as one of the earliest biomarkers of CKD progression. |