Effects of sucroferric oxyhydroxide and sevelamer carbonate on chronic kidney disease-mineral bone disorder parameters in dialysis patients

Abstract

Background: Treatment of hyperphosphataemia is the primary goal of chronic kidney disease-mineral and bone disorder (CKD-MBD) management. This post hoc analysis of a randomized, Phase 3 study evaluated the effects of 1-year treatment with the phosphate binders sucroferric oxyhydroxide or sevelamer carbonate ('sevelamer') on CKD-MBD indices among dialysis patients with hyperphosphataemia.

Methods: After a 2- to 4-week washout from previous phosphate binders, 1059 patients were randomized 2:1 to sucroferric oxyhydroxide 1.0-3.0 g/day (n = 710) or sevelamer 2.4-14.4 g/day (n = 349) for up to 24 weeks. Eligible patients enrolled in a 28-week extension. This post hoc analysis was performed for patients who completed ≥1 year of continuous treatment (n = 549). As the treatment groups showed similar CKD-MBD outcomes, the data were pooled for this analysis.

Results: Phosphate-binder therapy was associated with significant and sustained 30% reductions in serum phosphorus (P < 0.001). Median intact fibroblast growth factor-23 (FGF-23) also significantly decreased (P < 0.001) by 64% over 1 year. Intact parathyroid hormone decreased significantly after 24 weeks (P < 0.001), but levels returned to near baseline values by Week 52; minimal changes in serum calcium were observed. Of the bone resorption markers evaluated, tartrate-resistant acid phosphatase 5b (TRAP5b) decreased significantly (P < 0.001), whereas CTx increased transiently but returned to baseline levels by Week 52. The bone formation markers bone-specific alkaline phosphatase and osteocalcin both increased over 1 year of treatment.

Conclusions: Overall, 1 year of sucroferric oxyhydroxide or sevelamer treatment significantly reduced serum FGF-23, which has been associated with clinical benefit in patients with CKD. The trend towards increased bone formation marker levels indicates a beneficial effect on bone metabolism.

Keywords: bone markers; dialysis; hyperphosphataemia; phosphate binder; sucroferric oxyhydroxide.

FIGURE 1

Median serum concentration for serum phosphorus (A), FGF-23 (B), iPTH (C), calcium (D), 25-hydroxyvitamin D (E) and 1, 25-dihydroxyvitamin D (F) (completer set, n = 549). Error bars represent 25th and 75th percentiles. P-values are versus baseline: **P < 0.01, ****P < 0.0001.

FIGURE 2

Change in log serum FGF-23 versus change in serum phosphorus (sP) at Week 52 (n = 518).

FIGURE 3

Median serum concentration of markers of bone resorption, TRAP-5b (A) and CTx (B), and of bone formation, OST (C) and BSAP (D) (completer set, n = 549). Error bars represent 25th and 75th percentiles. P-values are versus baseline: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.