Salivary Phosphate-Binding Chewing Gum Reduces Hyperphosphatemia in Dialysis Patients

Abstract

In uremic patients, hyperphosphatemia is associated with cardiovascular calcification and increased cardiovascular mortality. Despite the use of phosphate binders, only half of hemodialysis (HD) patients achieve recommended serum phosphate levels. A hyperphosphoric salivary content, which correlates linearly with serum phosphate, has been reported in HD patients. We hypothesized that binding salivary phosphate during periods of fasting in addition to using phosphate binders with meals could improve the treatment of hyperphosphatemia. We assessed the phosphate-binding capacity of the natural polymer chitosan by 31 P nuclear magnetic resonance and established that 10 and 20% (wt/vol) middle viscosity chitosan solutions bind 30 and 50% of the phosphate contained in PBS, respectively. Thirteen HD patients with serum phosphate levels Ͼ6.0 mg/dl despite treatment with sevelamer hydrochloride chewed 20 mg of chitosan-loaded chewing gum twice daily for 2 wk at fast in addition to their prescribed phosphate-binding regimen. Salivary phosphate and serum phosphate significantly decreased during the first week of chewing; by the end of 2 wk, salivary phosphate decreased 55% from baseline (73.21 Ϯ 19.19 to 33.19 Ϯ 6.53; P Ͻ 0.00001), and serum phosphate decreased 31% from baseline (7.60 Ϯ 0.91 to 5.25 Ϯ 0.89 mg/dl; P Ͻ 0.00001). Salivary phosphate returned to baseline by day 15 after discontinuing the chewing gum, whereas serum phosphate levels took 30 d to return to baseline. Parathyroid hormone and serum calcium concentrations were not affected by the gum. In conclusion, adding salivary phosphate binding to traditional phosphate binders could be a useful approach for improving treatment of hyperphosphatemia in HD patients.

Effects of Expelling of Induced Hypersalivation on Serum Phosphorus, Urea and Creatinine Levels in End Stage Renal Disease Patients

“…These results were in (9) who found that serum phosphate significantly decreased during the first weeks of chewing chitosan gum in ESRD patients and returned to baseline after discontinuing the chewing gum. Our results were not in agreement with Akizawa T et al,2014 (10) who found that chewing gum and expelling saliva does not affect serum and salivary phosphorus levels in Japanese HD patients with hyperphosphatemia.…”

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

“…Blood samples from 13 previously studied chronic HD patients, 8 9 males and 4 females, age range 30-71 years, dialytic age range 12-264 months, were used for the determination of hsCRP and its relationship with hyperphosphatemia and Ca × PO 4 . The etiology of ESRD for the patients was as follows: chronic glomerulonephritis (four patients); nephroangiosclerosis (seven patients); polycystic kidney disease (one patient); undiagnosed (one patient).…”

“…The etiology of ESRD for the patients was as follows: chronic glomerulonephritis (four patients); nephroangiosclerosis (seven patients); polycystic kidney disease (one patient); undiagnosed (one patient). As in the Methods section of our previously published papers and in accordance with the previously reported protocols, [6][7][8] exclusion criteria for the enrollment of the patients comprised the diagnosis of acute infections, malignancies, ongoing inflammatory processes, and Sjögren syndrome, which directly may influence CRP level.…”

“…Clinical characteristics, dialysis procedure, and treatment with chitosan-loaded chewing gum timing protocol are detailed in Savica, Calò et al 8 In brief, bicarbonate dialysis using polysulfone dialyzers treated patients (210-240 minutes three times a week, single-pool KT/V ratio 1.39 ± 0.15) who, despite treatment with sevelamer hydrochloride, 8 had serum phosphate levels >6.0 mg/dL, chewed 20 mg of chitosan-loaded chewing gum twice daily for 2 weeks at fasting in addition to their phosphate-binding regimen. PO 4 and Ca × PO 4 were evaluated at the beginning of the study, after 1 and 2 weeks of chewing gum use and after 2 and 4 weeks from the chewing gum use withdrawal.…”

“…7 We have shown in sevelamer-resistant dialysis patients that treatment with a chewing gum loaded with chitosan, a salivary phosphate binder, as an add-on to sevelamer, markedly reduced salivary PO 4 level as well as serum PO 4 and Ca × PO 4 to normal. 8 To give support to a direct proinflammatory role of hyperphosphatemia "per se" in humans, we have considered in this study our previously studied dialysis patients with sevelamer hydrochloride-"resistant" hyperphosphatemia in whom serum PO 4 was normalized by the treatment with a chewing gum loaded with chitosan, a salivary phosphate binder, as an add-on to sevelamer, 8 to retrospectively evaluate their high sensitive (hs) CRP and the relationship with hyperphosphatemia and Ca × PO 4 .…”