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Abstract: SA-PO174

Sucroferric Oxyhydroxide Therapy Reduces Endogenous Calciprotein Particle Formation in Dialysis Patients and Attenuates Calcification and Inflammation in Vascular Cells In Vitro

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Thiem, Ursula, Ordensklinikum Linz GmbH Elisabethinen, Linz, Austria
  • Hewitson, Timothy D., The Royal Melbourne Hospital, Parkville, Victoria, Australia
  • Toussaint, Nigel David, The Royal Melbourne Hospital, Parkville, Victoria, Australia
  • Holt, Stephen Geoffrey, The University of Melbourne, Melbourne, Victoria, Australia
  • Haller, Maria C., Ordensklinikum Linz GmbH Elisabethinen, Linz, Oberösterreich, Austria
  • Pasch, Andreas, Calciscon AG, Nidau, Switzerland
  • Cejka, Daniel, Ordensklinikum Linz GmbH Elisabethinen, Linz, Oberösterreich, Austria
  • Smith, Edward R., The Royal Melbourne Hospital, Parkville, Victoria, Australia
Background

Calciprotein particles (CPP), colloidal mineral-protein nanoparticles, have emerged as potential mediators of phosphate toxicity in patients on dialysis, with putative links to vascular calcification, endothelial dysfunction, and inflammation. We hypothesized that treatment with the non-calcium-containing phosphate binder sucroferric oxyhydroxide (SO) would reduce endogenous CPP levels, also manifesting in attenuated pro-calcific and pro-inflammatory effects of patient serum towards human vascular cells in vitro.

Methods

Secondary analysis of a randomized, controlled cross-over study in 28 hemodialysis patients comparing the effect of two-week binder washout with high-dose (2000 mg/d) and low-dose (250 mg/d) SO therapy on serum CPP, inflammatory cytokine/chemokine arrays and in vitro bioassays using aortic smooth muscle cells (HASMC) and human coronary endothelial cells (HCAEC).

Results

In our cohort (75% male, 62±12 years) high-dose SO reduced primary (amorphous) and secondary (crystalline) CPP [-62 (-76 to -44)%, p<0.0001 and -38 (-62 to -0.14)%, p<0.001, respectively] compared to washout. Nine of 14 plasma cytokines/chemokines significantly decreased with high-dose SO, with consistent reductions in Interleukin-6 [IL-6, -31(-51 to -1)%, p<0.001] and Interleukin-8 [IL-8, -46 (-73 to -17)%, p<0.0001]. Compared to treatment with serum collected after washout, exposure of HASMC and HCAEC cultures to serum of SO-treated patients reduced calcification and markers of activation (IL-6, IL-8 and vascular cell adhesion protein 1), respectively. Serum-induced HASMC calcification and HCAEC activation was ameliorated by removal of CPPs from patient sera and enhanced by uremic conditioning of synthetic CPP.

Conclusion

High-dose SO reduces endogenous CPP formation in dialysis patients and yielded serum with attenuated pro-calcific and inflammatory effects in vitro.

Funding

  • Commercial Support