Received February 4, 2008
Accepted on September 11, 2008

CLINICAL RESEARCH

Salivary Phosphate-Binding Chewing Gum Reduces Hyperphosphatemia in Dialysis Patients

Vincenzo Savica ^*, Lorenzo A. Calò ¹, Paolo Monardo , Paul A. Davis , Antonio Granata ^||, Domenico Santoro ^*, Rodolfo Savica ^¶, Rosa Musolino ^¶, Maria Cristina Comelli ^**, and Guido Bellinghieri ^*

Departments of *Nephrology and ¶Neurology and ||Department of Clinical-Experimental Medicine and Pharmacology, Clinica Medica, University of Messina, and Nephrology and Dialysis Units, Papardo Hospital, Messina, and Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova, Padova, Italy; Department of Nutrition, University of California, Davis, Davis, California; and **CM&D Pharma Limited, Chertsey, UK, United Kingdom

¹ To whom correspondence should be addressed. E-mail: renzcalo{at}unipd.it.

	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 ³¹P 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 >6.0 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 ± 19.19 to 33.19 ± 6.53; P < 0.00001), and serum phosphate decreased 31% from baseline (7.60 ± 0.91 to 5.25 ± 0.89 mg/dl; P < 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.