Phosphate Salivary Secretion in Hemodialysis Patients: Implications for the Treatment of Hyperphosphatemia

Abstract

Background/Aims: Hyperphosphatemia is recognized as contributing to the increased risk of cardiac death in end-stage renal disease (ESRD) and hemodialysis (HD) patients. Currently available pharmacologic treatment for hyperphosphatemia is based on phosphate binders but, despite treatment, only half of the patients fall within the range for serum phosphorus of the K/DOQI guidelines. Therefore, there is a need to identify other therapeutic approaches in order to reduce serum phosphate. Salivary fluid contains phosphate which, if related to the daily salivary secretion (1,000–1,880 ml), may raise interest in order to identify further additive approaches to phosphorus removal in uremic patients, while data about salivary phosphate secretion in ESRD patients are controversial. Methods: This study evaluates salivary phosphate secretion in 68 HD patients compared with 30 healthy subjects. Saxon’s test confirmed normal salivary function in patients and controls. Salivary calcium and serum phosphate, calcium and PTH were also measured. Results: HD patients had significantly higher salivary phosphorus levels compared with healthy controls: 30.35 (26.5–34.6) vs. 12.1 (10.58–14.73) mg/dl (p < 0.0001), and this significantly correlated (p < 0.0001) with serum phosphorus. Multiple regression analysis confirmed serum phosphorus as the only predictor (p < 0.0001) of salivary phosphorus. Conclusions: Given the functional secretive similarity between salivary glands and the kidneys, this increased salivary phosphate secretion might be interpreted as being compensatory in the presence of renal failure. Absorption of the increased salivary phosphate secretion, however, may worsen hyperphosphatemia; therefore, the binding of salivary phosphate might be considered as a further therapeutic approach to hyperphosphatemia in ESRD.

Salivary Phosphate-Binding Chewing Gum Reduces Hyperphosphatemia in Dialysis Patients

“…Although salivary PO 4 levels correlate with serum PO 4 values in HD patients, 9 no significant variability was observed in patients' serum PO 4 in the 6 mo before study entry, thereby supporting patients' compliance to diet and sevelamer use. Hyperphosphoric saliva seems to be an epiphenomenon in CKD and ESRD, 8,9 thus specifically suggesting local binding to affect PO 4 balance positively. As a proof of concept, salivary PO 4 immediately regained baseline values at chewing gum discontinuation, whereas an additional 2 wk was required for serum PO 4 to regain baseline values progressively (week 6).…”

“…16 We previously reported that increased serum PO 4 levels are reflected in increased salivary PO 4 content in patients with CKD and HD patients. 8,9 Despite undergoing dialysis three times a week and being regularly treated with sevelamer hydrochloride for at least 12 mo at study entry and before chewing gum use, our HD patients had a mean salivary PO 4 level of 73.21 Ϯ 19.19 mg/dl and a mean serum PO 4 level of 7.6 Ϯ 0.9 mg/dl, thus remaining at high risk for cardiovascular disease and cardiac mortality. Daily salivary secretion volumes range between 500 and 700 ml, 16 and even higher rates have been reported in healthy populations, 17 whereas low salivary flow rate has been documented in HD patients with diabetes.…”

“…Salivary PO 4 levels correlated with serum creatinine and GFR in CKD 8 and with serum PO 4 levels in HD patients, the salivary PO 4 content being at least five times the serum PO 4 level. 9 In this article, we suggest that in HD patients with serum PO 4 Ն6 mg/dl and salivary PO 4 Ն30 mg/dl, a sustained intestinal absorption of immediately bioavailable PO 4 could account for an additional load to the dietary PO 4 intake, via the ingestion of the 500 to 700 ml of saliva produced daily. Among other underestimated dietary contributions to PO 4 burden, 10 a looping of gastrointestinally secreted and intestinally absorbed PO 4 could partially explain the unsatisfactory efficiency of sevelamer hydrochloride administered at meals to reduce the intestinal absorption of PO 4 generated by food intake in longterm HD patients.…”

“…6 Nevertheless, only approximately 50% of HD patients achieve the serum PO 4 levels currently recommended by Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. 7 An increased salivary PO 4 excretion has been reported in patients with CKD 8 and HD patients, 9 independent from food intake. Salivary PO 4 levels correlated with serum creatinine and GFR in CKD 8 and with serum PO 4 levels in HD patients, the salivary PO 4 content being at least five times the serum PO 4 level.…”

Understanding Sources of Dietary Phosphorus in the Treatment of Patients with Chronic Kidney Disease

“…After intestinal P absorption, only small amounts of P are excreted into the feces, sweat, and saliva, but this proportion of total P output can be increased with worsening renal function (19). In individuals without far advanced kidney failure, Ͼ95% of the excretion of the absorbed P is through urine (20).…”