title: FGF23 antagonism: the thin line between adaptation and maladaptation in chronic kidney disease.
abstract: For more than 10 years, we have been convinced by overwhelming epidemiological evidence with a high biological plausibility that hyperphosphataemia imposes one of the most sustained cardiovascular and mortality risks on patients suffering from chronic kidney disease (CKD). With the discovery of the fibroblast growth factor-23 (FGF23)/klotho axis, we not only gained a new and mechanistic understanding of phosphate handling of the body, we also felt that novel therapeutic strategies may arise counteracting the deleterious consequences of phosphate retention, dysregulation and maldistribution. Two recent experimental studies shed additional and important light on what we can expect from such new insights. Faul et al. showed us that FGF23 excess may directly induce left ventricular hypertrophy (LVH) and that FGF-receptor antagonism ameliorates CKD-induced LVH in rats. Shalhoub et al. demonstrated that FGF23 antibodies successfully ameliorated the development and progression of most features of secondary hyperparathyroidism in a rat model of CKD, however, at the expense of hyperphosphataemia, progressive vascular calcification and death. Such studies not only help to continuously improve our understanding, but also especially sharpen our perception of how thin the line may be between adaptation and maladaptation in chronic disease scenarios.
authors.affiliation: Division of Nephrology, Klinikum Coburg GmbH, Coburg, Germany. markus.ketteler@klinikum-coburg.de
authors.forename: Markus
authors.initials: M
authors.lastname: Ketteler
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Biggar
authors.forename: Orfeas
authors.initials: O
authors.lastname: Liangos
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000150:complications*
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23