title: Cross talk between the renin-angiotensin-aldosterone system and vitamin D-FGF-23-klotho in chronic kidney disease.
abstract: There is increasingly evidence that the interactions between vitamin D, fibroblast growth factor 23 (FGF-23), and klotho form an endocrine axis for calcium and phosphate metabolism, and derangement of this axis contributes to the progression of renal disease. Several recent studies also demonstrate negative regulation of the renin gene by vitamin D. In chronic kidney disease (CKD), low levels of calcitriol, due to the loss of 1-alpha hydroxylase, increase renal renin production. Activation of the renin-angiotensin-aldosterone system (RAAS), in turn, reduces renal expression of klotho, a crucial factor for proper FGF-23 signaling. The resulting high FGF-23 levels suppress 1-alpha hydroxylase, further lowering calcitriol. This feedback loop results in vitamin D deficiency, RAAS activation, high FGF-23 levels, and renal klotho deficiency, all of which associate with progression of renal damage. Here we examine current evidence for an interaction between the RAAS and the vitamin D-FGF-23-klotho axis as well as its possible implications for progression of CKD.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen and University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. m.h.de.borst@int.umcg.nl
authors.forename: Martin H
authors.initials: MH
authors.lastname: de Borst
authors.forename: Marc G
authors.initials: MG
authors.lastname: Vervloet
authors.forename: Piet M
authors.initials: PM
authors.lastname: ter Wee
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
mesh_terms: D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D000090265:Klotho Proteins; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*; D012084:Renin-Angiotensin System; D014807:Vitamin D / Q000378:metabolism*
chemical_list: C000717427:FGF23 protein, human; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins