title: Response of fibroblast growth factor 23 to volume interventions in arterial hypertension and diabetic nephropathy.
abstract: Fibroblast growth factor 23 (FGF-23) rises progressively in chronic kidney disease and is associated with adverse cardiovascular outcomes. FGF-23 putatively induces volume retention by upregulating the sodium-chloride cotransporter (NCC). We studied whether, conversely, interventions in volume status affect FGF-23 concentrations.We performed a post hoc analysis of 1) a prospective saline infusion study with 12 patients with arterial hypertension who received 2 L of isotonic saline over 4 hours, and 2) a randomized controlled trial with 45 diabetic nephropathy (DN) patients on background angiotensin-converting enzyme -inhibition (ACEi), who underwent 4 6-week treatment periods with add-on hydrochlorothiazide (HCT) or placebo, combined with regular sodium (RS) or low sodium (LS) diet in a cross-over design. Plasma C-terminal FGF-23 was measured by ELISA (Immutopics) after each treatment period in DN and before and after saline infusion in hypertensives.The patients with arterial hypertension were 45 ± 13 (mean ± SD) years old with an estimated glomerular filtration rate (eGFR) of 101 ± 18 mL/min/1.73 m. Isotonic saline infusion did not affect FGF-23 (before infusion: 68 median [first to third quartile: 58-97] relative unit (RU)/mL, after infusion: 67 [57-77] RU/mL, P = 0.37). DN patients were 65 ± 9 years old. During ACEi + RS treatment, eGFR was 65 ± 25 mL/min/1.73 m and albuminuria 649 mg/d (230-2008 mg/d). FGF23 level was 94 (73-141) RU/mL during ACEi therapy. FGF-23 did not change significantly by add-on HCT (99 [74-148] RU/mL), LS diet (99 [75-135] RU/mL), or their combination (111 [81-160] RU/mL, P = 0.15).Acute and chronic changes in volume status did not materially change FGF-23 in hypertensive patients and DN, respectively. Our data do not support a direct feedback loop between volume status and FGF-23 in hypertension or DN.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Department of Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany Department of Nephrology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Jelmer K
authors.initials: JK
authors.lastname: Humalda
authors.forename: Sarah
authors.initials: S
authors.lastname: Seiler-Muler
authors.forename: Arjan J
authors.initials: AJ
authors.lastname: Kwakernaak
authors.forename: Marc G
authors.initials: MG
authors.lastname: Vervloet
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Heine
authors.forename: Martin H
authors.initials: MH
authors.lastname: de Borst
mesh_terms: D000368:Aged; D018592:Cross-Over Studies; D003928:Diabetic Nephropathies / Q000097:blood* / Q000628:therapy*; D004039:Diet, Sodium-Restricted; D004232:Diuretics / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000097:blood* / Q000628:therapy*; D007552:Isotonic Solutions / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D004232:Diuretics; C000717427:FGF23 protein, human; D007552:Isotonic Solutions; D006852:Hydrochlorothiazide; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23