Fibroblast growth factor 23 and parathyroid hormone after treatment with active vitamin D and sevelamer carbonate in patients with chronic kidney disease stage 3b, a randomized crossover trial

Abstract

Background: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that is secreted from bone and serum level increases as renal function declines. Higher levels of FGF23 are associated with increased mortality in hemodialysis-patients and in patients with chronic kidney disease (CKD) stage 2-4. The use of active vitamin D and phosphate binders as recommended in international guidelines, may affect the level of FGF23 and thereby clinical outcome. We investigated the effects of a phosphate binder and active vitamin D on the serum levels of intact FGF23 (iFGF23) and intact parathyroid hormone (iPTH) in patients with CKD stage 3b (glomerular filtration rate (GFR) 30-44 ml/min/1.73 m(2)).

Methods: Seven women and 14 men were included, mean age 65.6 ± 12.2 years. They were randomized in a 1:1 ratio to receive one of two treatment sequences. Group-1 (the alphacalcidol-sevelamer carbonate group): alphacalcidol 0.25 μg once daily for two weeks followed by sevelamer carbonate 800 mg TID with meals for two weeks after a two-week washout period. Group-2 (the sevelamer carbonate-alphacalcidol group): vice versa. Nineteen patients completed the study. The 25-hydroxyvitamin D level at baseline was 97.6 ± 25.0 nmol/l.

Results: There were no treatment effects on the iFGF23 and iPTH levels overall. In group-1 the iFGF23 level was higher after treatment with alphacalcidol compared with sevelamer carbonate (mean 105.8 ± 41.6 vs. 79.1 ± 36.5 pg/ml, p = 0.047 (CI: 0.4-52.9), and the iPTH level was lower (median: 26.5, range: 14.6-55.2 vs. median 36.1, range 13.4-106.9 pg/ml, p = 0.011). In group-2 the iFGF23 level increased non-significantly after treatment with sevelamer carbonate and throughout the washout period.

Conclusions: In this crossover trial with alphacalcidol and sevelamer carbonate in patients with CKD stage 3b, the levels of iFGF23 were not significantly different after the two treatments. However, in the group of patients initiating therapy with sevelamer carbonate the iFGF23 levels seemed to increase while this response was mitigated in the group of patients given alphacalcidol followed by sevelamer carbonate. This may have therapeutic implications on choice of first line therapy. The number of patients is small and this conclusion is in part based on subgroup analysis. It is therefore important that these results are confirmed in larger studies.

Trial registration number: European Clinical Trial Database (EudraCT) 2010-020415-36 and Clinical Trials.gov NCT01231438.

Figure 1

Delta iFGF23 levels. Box plot of Δ intact fibroblast growth factor 23 (iFGF23): mean iFGF23 level after the first treatment period minus mean iFGF23 level after the second treatment period. Group-1: the alphacalcidol – sevelamer carbonate group: alphacalcidol for two weeks (first treatment period) followed by sevelamer carbonate for two weeks (second treatment period) after two weeks washout. Group-2: the sevelamer carbonate – alphacalcidol group: sevelamer carbonate for two weeks (first treatment period) followed by alphacalcidol for two weeks (second treatment period) after two weeks washout.

Figure 2

Mean iFGF23 levels and study design. The mean level of intact fibroblast growth factor 23 (FGF23) for each group at baseline (week 0), after the first treatment period (week 2), after washout (week 4) and after the second treatment period (week 6). Bars indicate SEM. Group-1: the alphacalcidol – sevelamer carbonate group: alphacalcidol for two weeks (first treatment period) followed by sevelamer carbonate for two weeks (second treatment period) after two weeks washout. Group-2: the sevelamer carbonate – alphacalcidol group: sevelamer carbonate for two weeks (first treatment period) followed by alphacalcidol for two weeks (second treatment period) after two weeks washout.