title: Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease.
abstract: Hyperphosphatemia, calcitriol deficiency, and secondary hyperparathyroidism (SHPT) are common complications of chronic kidney disease (CKD). Fibroblast growth factor-23 (FGF-23) is a novel phosphaturic hormone that also inhibits renal 1alpha-hydroxylase activity and thus may be involved in the pathogenesis of SHPT. Several hypotheses were tested: that FGF-23 increases as renal function declines; is linearly associated with serum phosphate levels; is associated with increased phosphaturia independent of parathyroid hormone (PTH); and is associated with decreased calcitriol levels independent of renal function, hyperphosphatemia, and vitamin D stores. FGF-23, PTH, 25(OH)D3, calcitriol, calcium, phosphate, and urinary fractional excretion of phosphate (Fe(PO4)) were measured in 80 CKD patients. Multiple linear regression was used to test the hypotheses. FGF-23 and PTH were inversely associated with estimated GFR (eGFR), whereas calcitriol levels were linearly associated with eGFR. Hyperphosphatemia and hypocalcemia were present in only 12 and 6% of patients, respectively, all of whose eGFR was <30. Increased Fe(PO4) was associated with decreased eGFR, and both increased FGF-23 and PTH were independently associated with increased Fe(PO4). Increased FGF-23 and decreased 25(OH)D3 were independent predictors of decreased calcitriol, but the effects on calcitriol levels of renal function itself and hyperphosphatemia were completely extinguished by adjusting for FGF-23. It is concluded that FGF-23 levels increase early in CKD before the development of serum mineral abnormalities and are independently associated with serum phosphate, Fe(PO4), and calcitriol deficiency. Increased FGF-23 may contribute to maintaining normal serum phosphate levels in the face of advancing CKD but may worsen calcitriol deficiency and thus may be a central factor in the early pathogenesis of SHPT.
authors.affiliation: Department of Medicine Internal Medicine Residency Training Program, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
authors.forename: Orlando
authors.initials: O
authors.lastname: Gutierrez
authors.forename: Tamara
authors.initials: T
authors.lastname: Isakova
authors.forename: Eugene
authors.initials: E
authors.lastname: Rhee
authors.forename: Anand
authors.initials: A
authors.lastname: Shah
authors.forename: Julie
authors.initials: J
authors.lastname: Holmes
authors.forename: Gina
authors.initials: G
authors.lastname: Collerone
authors.forename: Harald
authors.initials: H
authors.lastname: Jüppner
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002117:Calcitriol / Q000172:deficiency* / Q000378:metabolism; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000378:metabolism*; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010760:Phosphorus Metabolism Disorders / Q000378:metabolism*
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol