Learn about the
2008T Fresenius Hemodialysis

Interview with
Jeffrey H. Burbank
Founder& CEO of NxStage

What are the main findings of the study?

Answer: FGF-23 can be measured with a C-terminal (c-FGF-23) or an intact (i-FGF-23) assay. We wanted to assess which is the best assay in dialysis patients. Both assays showed a positive, significant correlation between FGF-23 and PTH and a negative correlation between FGF-23 and 25-hydroxy-vitamin D.

The two assays had different correlations regarding 1,25-dihydroxy-vitamin D (negatively related to c-FGF-23) and phosphate (positively related to i-FGF-23). Neither c-FGF-23 or i-FGF-23 were significantly related to a higher mortality although c-terminal FGF-23 did have a worsening trend towards mortality.

Were any of the findings unexpected?

Answer: the findings were partly unexpected since our results differ from previous reports in dialysis patients which found correlation of FGF-23 with phosphate levels but not with PTH and calcium levels.

Also, there was no association between survival and the levels of FGF-23 while this has been reported in earlier studies. However, we studied a small population of 77 patients and the study may be underpowered to detect a link between FGF-23 and mortality.

What should clinicians and patients take away from this study?

Answer: Levels of c-terminal and intact FGF-23 are not clearly indicative of FGF-23 effects on markers of the chronic kidney disease mineral bone disorder (CKD-MBD). Measurement of intact FGF-23 was not superior in showing interactions with these markers.

Because of conflicting results about the significance of FGF-23, it is of importance to improve the diagnostic capabilities if we want to better understand the exact role of FGF-23 in mineral metabolism.

What recommendations do you have for nephrology health care providers as a result of your study?

Answer: Although measurement of FGF-23 gives some indications of FGF-23 bioactivity in dialysis patients, measurement of FGF-23 on a regular basis with the current assays in chronic kidney disease and dialysis patients does not yet appear to be clinically useful.

Aims: Considering the growing relevance of fibroblast growth factor-23 (FGF-23) in the pathogenesis of chronic kidney disease bone and mineral disorder (CKD-MBD), an analysis was performed to determine the relative importance of C-terminal (cFGF-23) and intact (iFGF-23) assays in assessing CKD-MBD status in the first place and the relationship between FGF-23 and mortality as a secondary aim.

Methods: In 77 patients (15 peritoneal dialysis and 62 hemodialysis), levels of calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin- D (25D), 1,25D, FGF-23 (C-terminal and intact molecule) were measured and their correlations were analyzed. The relationship between FGF-23 levels and patient survival was also analyzed.

Results: A significant correlation was found between cFGF-23 and 1,25D, PTH and 25D while iFGF-23 was significantly correlated with phosphate, 25D and PTH. PTH and 1,25D were independent predictors of cFGF-23, while for iFGF-23 independent predictors were phosphate and 25D. No significant relationship was found between FGF-23 and mortality.

Conclusions: C-terminal or intact FGF-23 levels are weakly correlated and thus not clearly indicative of FGF-23 effects on PTH, P and vitamin D metabolism in dialysis patients. Assays for cFGF-23 and iFGF-23 showed a good correlation, but the intact molecule was not superior in defining interactions with CKD-MBD molecules.

Measuring FGF-23 on a regular basis with the current assays in CKD and dialysis patients does not yet seem clinically useful.

Author Interview: Dr. Biagio Di Iorio
Acute Effects of Very-Low-Protein Diet on FGF23 Levels: A Randomized Study