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

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 x phosphate (Ca x 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.