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J Clin Endocrinol Metab. 2012 Sep;97(9):3357-65. doi: 10.1210/jc.2012-1811. Epub 2012 Jun 11.

Biological variability of plasma intact and C-terminal FGF23 measurements.

Author information

1
Department of Renal Medicine, Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Level 2, 5 Arnold Street, Box Hill, 3128 Victoria, Australia. ed.smith@monash.edu

Abstract

CONTEXT:

FGF23 measurement may have a role in the management of patients with chronic kidney disease (CKD).

OBJECTIVE:

Our objective was to study the biological variability of plasma intact FGF23 (iFGF23) and C-terminal FGF23 (cFGF23) concentrations.

DESIGN:

Plasma samples were taken from 12 healthy adults at multiple time points on 2 consecutive days to assess diurnal variability of FGF23 concentrations. Early-morning fasting and nonfasting samples were also taken over a 6-wk period to estimate components of biological variation. Samples from 170 volunteers were used to define reference intervals. FGF23 concentrations were measured by commercial ELISA. Western blotting was used to analyze FGF23 species from the plasma of healthy adults and patients with predialysis CKD and those undergoing dialysis.

PARTICIPANTS AND SETTING:

A total of 180 healthy adults and 18 adults with stage 3-5D CKD participated in this study at a hospital research unit.

MAIN OUTCOME MEASURE:

Estimates were made of the biological variability of plasma FGF23 concentrations.

RESULTS:

iFGF23, but not cFGF23, showed significant diurnal variation. cFGF23 had a significantly lower intra-individual variation than iFGF23 (8.3 vs. 18.3%) but higher inter-individual variation than iFGF23 (28.9 vs. 19.2%). Fourteen samples would be needed to estimate an individual's homeostatic set point (within 10%) for iFGF23 compared with only three samples for cFGF23. Using Western blotting, C-terminal FGF23 fragments were detected in the plasma of individuals with normal renal function and at all stages of renal disease. The percent cFGF23 was significantly higher in those without renal impairment (P < 0.001) and was positively correlated with plasma phosphate concentration in those with normal renal function.

CONCLUSIONS:

The high intra-individual biological variability of iFGF23 may limit its clinical use as a diagnostic or management tool. Risk-related thresholds may be more appropriate for clinical decision making based on cFGF23 measurements than conventional reference intervals. FGF23 cleavage pathways may be an important natural regulatory mechanism for phosphate control.

PMID:
22689697
DOI:
10.1210/jc.2012-1811
[Indexed for MEDLINE]

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