Fibroblast growth factor-23 is associated with parathyroid hormone and renal function in a population-based cohort of elderly men.
OBJECTIVE
Fibroblast growth factor-23 (FGF23) is a circulating factor involved in phosphate (Pi) and vitamin D metabolism. Serum FGF23 is increased at later stages of chronic kidney disease due to chronic hyperphosphatemia and decreased renal clearance. Recent studies also indicate that FGF23 may directly regulate the expression of parathyroid hormone (PTH) in vitro. Therefore, the objective of the current study was to determine the relationship between FGF23, PTH, and other biochemistries in vivo in subjects with no history of renal disease.


METHODS
Serum biochemistries were measured in a subsample of the population-based Swedish part of the MrOS study. In total, 1000 Caucasian men aged 70-80 years were randomly selected from the population.


METHODS
Intact FGF23, Pi, calcium, albumin, estimated glomerular filtration rate (eGFR, calculated from cystatin C), PTH, and 25(OH)D3 were measured. Association studies were performed using linear univariate and multivariate regression analyses.


RESULTS
The median FGF23 level was 36.6 pg/ml, ranging from 0.63 to 957 pg/ml. There was a significant correlation between log FGF23 and eGFR (r=-0.21; P<0.00001) and log PTH (r=0.13; P<0.001). These variables remained as independent predictors of FGF23 in multivariate analysis. In addition, log PTH (beta=0.082; P<0.05) and eGFR (beta=-0.090; P<0.05) were associated with log FGF23 in subjects with eGFR>60 ml/min. Only eGFR (beta=-0.35; P<0.0001) remained as a predictor of log FGF23 in subjects with eGFR<60 ml/min.


CONCLUSIONS
Serum FGF23 and PTH are associated in vivo, supporting recent findings that FGF23 directly regulates PTH expression in vitro. Additionally, eGFR is associated with FGF23 in subjects with normal or mildly impaired renal function, indicating that GFR may modulate FGF23 levels independent of serum Pi.
Marsell
Richard
R
Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
Grundberg
Elin
E
Krajisnik
Tijana
T
Mallmin
Hans
H
Karlsson
Magnus
M
Mellström
Dan
D
Orwoll
Eric
E
Ohlsson
Claes
C
Jonsson
Kenneth B
KB
Ljunggren
Osten
O
Larsson
Tobias E
TE
D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000097:blood; D015331:Cohort Studies; D055316:Cystatin C; D015891:Cystatins / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000502:physiology*; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D010281:Parathyroid Hormone / Q000097:blood*; D010710:Phosphates / Q000097:blood; D012044:Regression Analysis; D012709:Serum Albumin / Q000378:metabolism; D013548:Sweden
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; C000717427:FGF23 protein, human; C470125:PTH protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D012709:Serum Albumin; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002118:Calcium