Abstract
BackgroundSerum fibroblast growth factor 23 (FGF-23) levels are markedly elevated in haemodialysis patients and have been linked to mortality outcomes. Small studies in health and chronic kidney disease, have demonstrated marked intra- and inter-individual variability in measured FGF-23 levels, and variable degradation in serum as compared to plasma samples. In end-stage kidney disease (ESKD), the intra- and inter-individual variability of FGF-23 levels, and the optimal collection methods remain poorly characterized. In this study we assessed the variability of FGF-23 levels in a cohort of stable haemodialysis patients. Secondly, in a subset of patients, we assessed the effects of different collection methods on measured FGF-23 levels.MethodsTo assess the variability of FGF-23, pre-dialysis blood samples were collected over 3 consecutive weeks from 75 haemodialysis patients. The effects of different specimen collection methods were examined in a subset of patients (n = 23), with pre-dialysis blood collected into different tubes: plain (serum), EDTA (plasma) and EDTA with the addition of a protease inhibitor (EDTA-PI). All analyses were performed in the main cohort and repeated in each subgroup. Variability over a 3-week period was assessed using repeated measures ANOVA and random effects linear regression models. Intra-class correlation coefficients were calculated to assess agreement, and coefficients of variation were calculated to assess intra- and inter-individual variability.ResultsOver the 3-week study period the mean FGF-23 levels were not significantly different in the serum (p = 0.26), EDTA (p = 0.62) and EDTA-PI (p = 0.55) groups. FGF-23 levels demonstrated marked intra- and inter-individual variability with a CV of 36 and 203.2%, respectively. In the subgroup analysis, the mean serum FGF-23 levels were significantly lower than the EDTA (p < 0.001) or EDTA-PI (p < 0.001) groups, however there was no difference in mean FGF-23 levels between EDTA and EDTA-PI (p = 0.54).ConclusionsThe measured FGF-23 levels were significantly lower in serum as compared to plasma, and the addition of a protease inhibitor did not confer an additional benefit. Importantly in this cohort of ESKD patients, FGF-23 levels showed marked intra- and inter-individual variability. The routine measurement of FGF-23 in ESKD remains challenging, however this study suggests the plasma is the optimal collection method for FGF-23 analysis.
Highlights
Serum fibroblast growth factor 23 (FGF-23) levels are markedly elevated in haemodialysis patients and have been linked to mortality outcomes
Variability The mean serum FGF-23 levels at week 1–3 were; 1615.5, 1390.5 and 1564.6 RU/ml, respectively and there was no significant difference over the 3-week period (p = 0.26)
In contrast to other studies, we found that FGF-23 stability in plasma was not improved by the addition of a protease inhibitor, it is possible that the supra-physiological levels of FGF-23 seen in this end-stage kidney disease (ESKD) cohort obfuscated any potential benefit
Summary
Serum fibroblast growth factor 23 (FGF-23) levels are markedly elevated in haemodialysis patients and have been linked to mortality outcomes. In large cohort studies, increased FGF-23 has been associated with increased risk of progression to end-stage kidney disease (ESKD) [6], and increased mortality in haemodialysis patients [7, 8] These findings have generated a lot of interest in its role as a potential novel biomarker of CKD mineral and bone disorder (CKD-MBD). Despite the emerging prominence of FGF-23 as a biomarker, the feasibility and clinical utility of routine FGF-23 measurements in CKD and ESKD cohorts remains unclear This is in part due to a lack of standardization of the available assays and uncertainty about sample collection and processing. A follow-up study demonstrated significant inter- and intra-individual variability [11] These studies highlight the ongoing uncertainty regarding optimal collection methods, processing and analysis of FGF-23 samples in health, CKD and ESKD
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