Fibroblast growth factor-23 in early chronic kidney disease: additional support in favor of a phosphate-centric paradigm for the pathogenesis of secondary hyperparathyroidism.
OBJECTIVE
The discovery of fibroblast growth factor-23 (FGF-23) and the elucidation of its function as a phosphaturic and 1,25(OH)2VitD counter-regulatory hormone provides a new conceptual framework for the understanding of the pathogenesis of secondary hyperparathyroidism. This study aims to elucidate the complex associations between FGF-23, parathyroid hormone (PTH), 1,25(OH)2D, and phosphate in patients with early-stage chronic kidney disease (CKD) and to provide clinical evidence in favor of the new phosphate-centric paradigm for the pathogenesis of secondary hyperparathyroidism.


METHODS
Serum biointact PTH and FGF-23, 25(OH)D, 1,25(OH)2D, calcium, phosphate, 24-hour urine excretion of phosphate and calcium, and urinary fractional excretion of phosphate were determined in a cross-sectional study including 125 patients with CKD stages 1 to 3.


RESULTS
Serum phosphate levels showed an inverse association with estimated GFR (eGFR), but were within the normal range in all but one patient. FGF-23 and PTH were inversely associated with eGFR, even in the subgroup of patients with CKD stages 1 and 2. High FGF-23 levels were significantly more prevalent than high PTH levels. The urinary fractional excretion of phosphate was highest in patients with both a high serum FGF-23 and PTH level. Increased FGF-23 and phosphate and decreased 25(OH)D were independently associated with decreased 1,25(OH)2D.


CONCLUSIONS
Our data are in favor of the new paradigm for the pathogenesis of secondary hyperparathyroidism according to which a reduced phosphate excretion capacity is the principal abnormality that initiates secondary hyperparathyroidism.
Evenepoel
Pieter
P
Department of Medicine, University Hos;pital Leuven, Leuven, Belgium. Pieter.Evenepoel@uz.kuleuven.ac.be
Meijers
Björn
B
Viaene
Liesbeth
L
Bammens
Bert
B
Claes
Kathleen
K
Kuypers
Dirk
D
Vanderschueren
Dirk
D
Vanrenterghem
Yves
Y
D000328:Adult; D000368:Aged; D001530:Belgium; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000652:urine; D016009:Chi-Square Distribution; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000209:etiology* / Q000652:urine; D007674:Kidney Diseases / Q000097:blood* / Q000150:complications / Q000503:physiopathology / Q000652:urine; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood* / Q000652:urine; D018570:Risk Assessment; D012307:Risk Factors
D015415:Biomarkers; C000717427:FGF23 protein, human; C470125:PTH protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol; D002118:Calcium
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