Endocrine Abstracts

Introduction: In CKD, net effects of declining kidney function and increasing FGF23 (and PTH) concentrations on vitamin D catabolism and iron metabolism are not clear.

Objectives: Compare the Biomedica to the Immutopics’ immunoassay for measurement of cFGF23. Determine the relationship between iron status; vitamin D and intact FGF23 (iFGF23) and c-terminal (cFGF23) concentrations in blood.

Method: Samples from routine care and a subset of patients with CKD (eGFR <70) were used in this study and compared to healthy controls. We used ELISA for measurements of cFGF23 (Biomedica, Vienna, Austria), cFGF23 and iFGF23 (Immutopics Inc., CA, USA). Ferritin, iron and transferrin were measured on a COBAS 6000 (Roche Diagnostics). 25(OH)D and 24,25(OH)2D3 were measured by LCMS.

Results: Biomedica cFGF23 ELISA showed a good correlation (n=125; r=0.966) to the Immutopics’ assay, however, a bias became apparent in the highest range of cFGF23. In CKD, we observed a parallel increase of iFGF23 and cFGF23 concentrations as eGFR decreased. Significant negative correlations were observed between cFGF23 and both iron concentration (r=−0.44, P<0.05) and transferrin saturation (r=−0.434, P<0.05). Concentrations of 25(OH)D and 24,25(OH)2D3 decreased by 34 and 68% respectively while the ratio 24,24(OH) 2D3:25(OH)D increased by 89% between healthy and CKD4.

Conclusion: We observed a negative correlation between FGF23 and iron metabolism suggesting that metabolism and/or excretion of FGF23 in CKD patients might be an iron dependent mechanism. We observed a strong vitamin D deficiency in CKD patients associated with a decrease in 24,25(OH)2D3 metabolite concentration. The ratio of 25(OH)D: 24,25(OH)2D is markedly elevated and increases as CKD progresses suggesting a relatively lower catabolic rate of 25(OH)D towards 24,25(OH)2D metabolite as CKD progresses. This may be in an attempt to allow relatively greater synthesis of 1,25(OH)2D to maintain its biological effects.