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

Nephrol Dial Transplant. 2019 Jul 1;34(7):1163-1170. doi: 10.1093/ndt/gfy127.

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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chelating Agents / therapeutic use
  • Chronic Kidney Disease-Mineral and Bone Disorder / complications
  • Chronic Kidney Disease-Mineral and Bone Disorder / metabolism
  • Chronic Kidney Disease-Mineral and Bone Disorder / therapy*
  • Drug Combinations
  • Female
  • Ferric Compounds / therapeutic use*
  • Fibroblast Growth Factor-23
  • Follow-Up Studies
  • Humans
  • Hyperphosphatemia / drug therapy*
  • Hyperphosphatemia / etiology
  • Male
  • Middle Aged
  • Parathyroid Hormone / blood
  • Phosphorus / blood
  • Renal Dialysis*
  • Sevelamer / therapeutic use*
  • Sucrose / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Chelating Agents
  • Drug Combinations
  • FGF23 protein, human
  • Ferric Compounds
  • Parathyroid Hormone
  • sucroferric oxyhydroxide
  • Phosphorus
  • Sucrose
  • Fibroblast Growth Factor-23
  • Sevelamer