Chronic kidney disease bone disease

Isabelle Piec, Allison Chipchase, Holly Nicholls, Christopher Washbourne, Jonathan Tang, William D. Fraser

Research output: Contribution to conferencePoster


Introduction and Aims: Fibroblast growth factor 23 (FGF23) is a major regulator of phosphate metabolism often elevated in genetic hypophosphataemic disorders and in chronic kidney disease. Recent studies have identified relationships between FGF23 and various markers of iron status and vitamin D. We aimed to compare the newly launched Biomedica immunoassay for the measurement of circulating c-terminal FGF23 (cFGF23) with Immutopics’ immunoassay and to determine the relationship between iron status, vitamin D metabolism, iFGF23 and cFGF23 concentrations in blood.

Methods: We used randomized samples from the routine care, a subset of patients with chronic kidney disease (CKD; eGFR < 70) and samples from healthy volunteers (n = 45) were used as controls. FGF23 concentrations were measured using a two-site enzyme-linked immunosorbent assay for cFGF23 (Biomedica, Vienna, Austria) and the 2nd generation ELISA for either cFGF23 or iFGF23 (Immutopics Inc., Ca, USA). Ferritin, iron and transferrin were measured on a COBAS 6000 (Roche Diagnostics). 25(OH)D (D2 and D3) and 24,25(OH)2D3 were measured by LCMS.

Results: We observed a good correlation (n = 134; r = 0.976 p &lt;0.0001) between the cFGF23 assays measured using the Biomedica kit as compared to the Immutopics’ assay. However, a bias became apparent for cFGF23 &gt; 30 pg/mL. Biomedica cFGF23 correlated to immuntopics iFGF23 in most cases (n = 35; r = 0.974) Nine patients presented with high cFGF23 without elevation of iFGF23. cFGF23 concentrations were significantly higher in CKD patient samples (mean ± SEM 7.2 ± 2.5) than controls (1.47 ± 2.1 pg/mL). Low Iron status was observed, 37% of CKD patients showed low iron concentration (13.8 ± 1.8 µmol/L; norm 11.5-30µmol/L) and a transferrin saturation &lt;16%; 24% showed elevated ferritin (with values &gt; 300µg/L). Decreasing eGFR (from 70 to 20) was accompanied by a small decrease in vitamin D status, 25(OH)D from 60 to 40 nmol/L and 24,25(OH)2D3 from 4 to 1 nmol/L; while the ratio of 25(OH)D:24,25(OH)2D3 (mean 23 ± 1) increased.

Conclusions: We observe a negative relationship between concentrations of ferritin, iron and transferrin saturation with cFGF23 in patients with CKD. cFGF23 is raised in patients with CKD, especially in patients with end-stage renal disease usually regarded as a compensatory response to hyperphosphatemia or phosphate overload. Due to 25(OH)D deficiency, patients with CKD develop secondary hyperparathyroidism which exacerbates bone loss bone disease. 24-hydroxylase, enzyme responsible for the catabolism of both 25(OH)D and 1,25(OH)2D, is rapidly induced by 1,25(OH)2D and FGF23 and suppressed by parathyroid hormone (PTH). In CKD, net effects of declining renal function and rising FGF23 and PTH concentrations on vitamin D catabolism are not clear. We observed that 24,25(OH)2D3 concentrations are further suppressed in CKD patient with vitamin D deficiency, suggesting metabolism favours the production of biologically active 1,25(OH)2D.
Original languageEnglish
Number of pages1
Publication statusPublished - 2016
Event53rd ERA-EDTA Congress - Vienna, Austria
Duration: 21 May 201624 May 2016


Conference53rd ERA-EDTA Congress

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