title: Fibroblast growth factor 23 and markers of mineral metabolism in individuals with preserved renal function.
abstract: Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate homeostasis. Circulating FGF23 is elevated in chronic kidney disease (CKD) and independently associated with poor renal and cardiovascular outcomes and mortality. Because the study of FGF23 in individuals with normal renal function has received little attention, we examined in a large, population-based study of 1128 participants the associations of FGF23 with markers of mineral metabolism and renal function. The median estimated glomerular filtration rate (eGFR) of the cohort was 105 ml/min per 1.73 m(2), and the median plasma FGF23 was 78.5 RU/ml. FGF23 increased and plasma 1,25-dihydroxyvitamin D3 decreased significantly below an eGFR threshold of 102 and 99 ml/min per 1.73 m(2), respectively. In contrast, plasma parathyroid hormone increased continuously with decreasing eGFR and was first significantly elevated at an eGFR of 126 ml/min per 1.73 m(2). On multivariable analysis adjusting for sex, age, body mass index, and GFR, FGF23 was negatively associated with 1,25-dihydroxyvitamin D3, and urinary absolute and fractional calcium excretion but not with serum calcium or parathyroid hormone. We found a positive association of FGF23 with plasma phosphate, but no association with urinary absolute or fractional phosphate excretion and, unexpectedly, a positive association with tubular maximum phosphate reabsorption/GFR. Thus, in the absence of CKD, parathyroid hormone increases earlier than FGF23 when the eGFR decreases. The increase in FGF23 occurs at a higher eGFR threshold than previously reported and is closely associated with a decrease in 1,25-dihydroxyvitamin D3. We speculate that the main demonstrable effect of FGF23 in the setting of preserved renal function is suppression of 1,25-dihydroxyvitamin D3 rather than stimulation of renal phosphate excretion.
authors.affiliation: Department of Nephrology, Hypertension, and Clinical Pharmacology, Bern University Hospital, University of Bern, Bern, Switzerland; Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Nasser A
authors.initials: NA
authors.lastname: Dhayat
authors.affiliation: Department of Nephrology, Hypertension, and Clinical Pharmacology, Bern University Hospital, University of Bern, Bern, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ackermann
authors.affiliation: Nephrology Service, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Menno
authors.initials: M
authors.lastname: Pruijm
authors.affiliation: Nephrology Service, Department of Specialties of Internal Medicine, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Belen
authors.initials: B
authors.lastname: Ponte
authors.affiliation: Cardiology Service, Department of Specialties of Internal Medicine, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Georg
authors.initials: G
authors.lastname: Ehret
authors.affiliation: Department of Community Medicine, Primary Care and Emergency Medicine, University Hospital of Geneva, Geneva, Switzerland; Institute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Idris
authors.initials: I
authors.lastname: Guessous
authors.affiliation: Department of Laboratory Medicine, Bern University Hospital, University of Bern, Bern, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Alexander Benedikt
authors.initials: AB
authors.lastname: Leichtle
authors.affiliation: Institute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Fred
authors.initials: F
authors.lastname: Paccaud
authors.affiliation: Department of Nephrology, Hypertension, and Clinical Pharmacology, Bern University Hospital, University of Bern, Bern, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Mohaupt
authors.affiliation: Department of Laboratory Medicine, Bern University Hospital, University of Bern, Bern, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Georg-Martin
authors.initials: GM
authors.lastname: Fiedler
authors.affiliation: Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.affiliation: Endocrinology Service, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Antoinette
authors.initials: A
authors.lastname: Pechère-Bertschi
authors.affiliation: Nephrology Service, University Hospital of Lausanne, Lausanne, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Burnier
authors.affiliation: Nephrology Service, Department of Specialties of Internal Medicine, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Martin
authors.affiliation: Institute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Murielle
authors.initials: M
authors.lastname: Bochud
authors.affiliation: Department of Nephrology, Hypertension, and Clinical Pharmacology, Bern University Hospital, University of Bern, Bern, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vogt
authors.affiliation: Department of Nephrology, Hypertension, and Clinical Pharmacology, Bern University Hospital, University of Bern, Bern, Switzerland; Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland. Electronic address: Daniel.Fuster@ibmm.unibe.ch.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Fuster
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002117:Calcitriol / Q000097:blood* / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000652:urine; D003430:Cross-Sectional Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000502:physiology*; D064368:Healthy Volunteers; D006801:Humans; D007668:Kidney / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood* / Q000378:metabolism / Q000652:urine; D065667:Renal Elimination / Q000502:physiology
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol; D002118:Calcium
keywords: FGF23; PTH; TmP/GFR; calcium; phosphate