The effect of phosphate binder therapy with sucroferric oxyhydroxide on calcification propensity in chronic haemodialysis patients: a randomized, controlled, crossover trial

Abstract

Background: Calcification propensity is associated with the risk for cardiovascular events and death in end-stage renal disease patients. Here we investigated the effect of lowering serum phosphate with oral phosphate binder therapy on calcification propensity.

Methods: We performed an open-label, randomized, controlled, crossover study in chronic haemodialysis patients with hyperphosphataemia. Patients (n = 39) were randomized in a 1:1 ratio to either low-dose (250 mg/day) sucroferric oxyhydroxide (SO) followed by high-dose (2000 mg/day) SO or vice versa, with washout phases before and after SO treatment. The primary endpoint was changed in calcification propensity as measured by calciprotein particle formation time (T₅₀ test) between washout and high-dose SO treatment in patients with ≥85% adherence to the prescribed SO dose (per-protocol analysis).

Results: In the primary per-protocol analysis (n = 28), 2000 mg/day SO treatment resulted in a mean increase in T₅₀ of 66 min (95% CI 49-84 min, P < 0.0001), from 243 ± 63 to 309 ± 74 min compared with phosphate binder washout. Serum phosphate decreased from 2.28 ± 0.5 to 1.63 ± 0.43 mmol/L (P < 0.0001). SO at 250 mg/day did not influence T₅₀ (P = 0.4) or serum phosphate concentrations (P = 0.9) compared with phosphate binder washout. The secondary intention-to-treat analysis (n = 39) showed similar results: an increase in T₅₀ of 52 min (95% CI 31-74 min, P < 0.0001) and a decrease in serum phosphate from 2.18 ± 0.5 to 1.64 ± 0.46 mmol/L. No major adverse cardiovascular event, case of calciphylaxis or death occurred during the study.

Conclusion: Phosphate binder treatment with SO improves serum calcification propensity of haemodialysis patients and might lead to improved outcomes.

Keywords: calcification propensity; haemodialysis; phosphate binder; sucroferric oxyhydroxide.

Graphical abstract

FIGURE 1:

Participant flow diagram according to Consolidated Standards of Reporting Trials recommendations.

FIGURE 2:

Effects of SO therapy on (A) T₅₀and (B) serum phosphateon an individual patient level between washout and SO 2000 mg/day. Asterisks indicate statistically significant differences (all P < 0.0001) between SO 2000 mg/day and the preceding washout phase. Δ: mean change between washout and SO 2000 mg/day.