Reduction of Hyperphosphatemia is Related with the Reduction of C-Reactive Protein in Dialysis Patients. Study in Sevelamer-Resistant Dialysis Patients Treated with Chitosan Chewing Gum as Salivary Phosphate Binder

Abstract

Background: In end-stage renal disease (ESRD) hyperphosphatemia associates with vascular calcifications and cardiovascular events derived from endothelial dysfunction. In dialysis patients, C-reactive protein (CRP), a marker of inflammation, associates with cardiovascular mortality. Increased PO4 concentration impairs endothelial integrity via induction of oxidative stress, and sevelamer, a phosphate binder, showed anti-inflammatory effect reducing CRP, which paralleled PO4 reduction. To give support to a direct proinflammatory role of hyperphosphatemia “per se,” we have considered previously studied dialysis patients with sevelamer-“resistant” hyperphosphatemia, who were treated with a chitosan-loaded chewing gum, as salivary phosphate binder, in addition to sevelamer, reduced serum PO4 to normal, to retrospectively evaluate their CRP and the relationship with hyperphosphatemia and calcium × phosphate (Ca × PO4) product. Patients and Methods: High sensitive (hs) CRP of 13 previously studied hemodialysis patients with sevelamer-resistant hyperphosphatemia was evaluated with immunonephelometry. Results: Chitosan chewing gum use reduced hsCRP (from 1.38 ± 0.61 to 0.39 ± 0.16 mg/L after the gum, p < 0.0002), which returned to baseline after 4 weeks from gum discontinuation (1.25 ± 0.41). hsCRP reduction paralleled serum PO4 reduction: from 7.60 ± 0.91 mg/dL to 5.18 ± 0.73 (after the gum) (p < 0.00001), returning to baseline (7.55 ± 0.75) after gum discontinuation. hsCRP reduction directly correlated with PO4 reduction (p = 0.029). Conclusion: The relationship in sevelamer-resistant dialysis patients between the reduction of serum PO4, induced by the chitosan-loaded chewing gum, and CRP reduction supports also in humans a proinflammatory role of hyperphosphatemia “per se” derived from “in vitro” studies. This further contributes to the high cardiovascular risk of ESRD patients making their serum phosphate in the normal range of vital importance.