MO722PHOSPHATE-BINDER THERAPY WITH SUCROFERRIC OXYHYDROXIDE REDUCES ENDOGENOUS CALCIPROTEIN PARTICLE FORMATION AND CRYSTALLIZATION IN A POST-HOC ANALYSIS OF A RANDOMIZED CONTROLLED TRIAL IN DIALYSIS PATIENTS

Abstract

Abstract Background and Aims Calcification propensity of serum can be measured with the so-called T50-test, which integrates the complex biological interplay of promoters and inhibitors of calciprotein particle formation in blood into a single readout. Calcification propensity is associated with the risk for cardiovascular events and death in dialysis patients. As we have recently demonstrated in a randomized, controlled, cross-over study in 39 chronic hemodialysis patients with hyperphosphatemia, lowering serum phosphate with high-dose phosphate-binder therapy with 2000 mg/d of sucroferric oxyhydroxide (SO) over two weeks reduces calcification propensity as determined by the T50-test compared to a two-week wash-out phase. Based on these results, we hypothesized that SO would influence endogenous calciprotein particle (CPP) formation and crystallization, i.e. conversion from primary to secondary CPP. Method To test this hypothesis, we conducted post-hoc analyses of the previously reported RCT (74% men, mean age 63±27 years, median dialysis vintage 24, IQR 16-36 months). Native serum CPP levels were measured by a fluorescent probe-based flow cytometric assay. Moreover, hydrodynamic radii (Rh) of secondary CPP formed after enrichment with exogenous calcium and phosphate was assessed by three-dimensional cross-correlation dynamic light scattering. Results Phosphate-binder therapy with SO lead to a reduction in serum phosphate levels from 2.28±0.5 mmol/l to 1.63±0.43 mmol/l (p<0.0001), accompanied by a significant reduction of endogenous calciprotein particle load and crystallization. Median (IQR) number of primary CPP decreased from 9.2x105 (7.7x105 - 12x105) particles/ml to 3.8 x105 (2.7x105 - 4.4x105) particles/ml (p<0.0001) and secondary CPP decreased from 5.4x104 (3.6x104 - 7.5x104) particles/ml to 3.2x104 (2.4x104 - 4.2x104) particles/ml (p<0.01, both by Wilcoxon matched-pairs test). Upon SO therapy we also observed a significant reduction of secondary calciprotein particle size as determined by Rh compared to phosphate-binder wash-out (214±55 nm vs. 231±52 nm, p<0.01 by paired t-test). Conclusion In chronic hemodialysis patients, lowering serum phosphate with SO is associated with a reduction in the load of primary and secondary CPP and a smaller size of secondary CPP.