title: Fibroblast growth factor 23.
abstract: There is growing interest in the role of fibroblast growth factor 23 (FGF23) in various diseases of disordered mineral metabolism. In chronic kidney disease (CKD), where biochemical evidence of mineral disturbances is especially common, FGF23 measurement has been advocated as an early and sensitive marker for CKD-related bone disease. In this setting, FGF23 analysis may also improve the discrimination of risk of adverse renal and cardiovascular outcomes and aid targeting of those patients that are likely to benefit from interventions. Nonetheless, while the physiological relevance of FGF23 in the control of mineral metabolism is now firmly established, relatively little attention has been paid to important preanalytical and analytical aspects of FGF23 measurement that may impact on its clinical utility. Here we review these issues and discuss the suitability of FGF23 testing strategies for routine clinical practice. The current 'state-of-the-art' enzyme-linked immunosorbent assay methods for FGF23 measurement show poor agreement due to differences in FGF23 fragment detection, antibody specificity and calibration. Such analytical variability does not permit direct comparison of FGF23 measurements made with different assays and is likely to at least in part account for some of the inconsistencies noted between observational studies. From a clinical perspective, the lack of concordance has implications for the development of standardized reference intervals and clinical decision limits. Finally, the inherent assay-dependent biological variability of plasma FGF23 concentration can further complicate the interpretation of results and the design of FGF23-based testing protocols. Currently, it would be premature to consider incorporating FGF23 measurements into standard testing repertoires.
authors.affiliation: Department of Renal Medicine, Eastern Health Clinical School, Faculty of Medicine Nursing and Health Sciences, Monash University, Box Hill, Victoria, Australia.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Smith
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: McMahon
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Holt
mesh_terms: D000818:Animals; D019963:Clinical Chemistry Tests; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D010281:Parathyroid Hormone / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000378:metabolism
chemical_list: C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: Fibroblast growth factor 23; chronic kidney disease; enzyme-linked immunosorbent assay; method comparison; parathyroid hormone