Savica Vincenzo, Calò Lorenzo A, Monardo Paolo, Davis Paul A, Granata Antonio, Santoro Domenico, Savica Rodolfo, Musolino Rosa, Comelli Maria Cristina, Bellinghieri Guido
Department of Nephrology, Clinica Medica, University of Messina, Messina, Italy.
J Am Soc Nephrol. 2009 Mar;20(3):639-44. doi: 10.1681/ASN.2008020130. Epub 2008 Nov 19.
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 >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.
在尿毒症患者中，高磷血症与心血管钙化及心血管死亡率增加相关。尽管使用了磷结合剂，但仅有一半的血液透析（HD）患者能达到推荐的血清磷水平。据报道，HD患者唾液中的高磷含量与血清磷呈线性相关。我们推测，除了进餐时使用磷结合剂外，在禁食期间结合唾液中的磷可能会改善高磷血症的治疗。我们通过³¹P核磁共振评估了天然聚合物壳聚糖的磷结合能力，确定10%（重量/体积）和20%（重量/体积）的中粘度壳聚糖溶液分别能结合PBS中30%和50%的磷。13名血清磷水平>6.0mg/dl的HD患者，尽管已接受盐酸司维拉姆治疗，但除了规定的磷结合治疗方案外，在禁食时每天咀嚼两次20mg的壳聚糖口香糖，持续2周。咀嚼的第一周，唾液磷和血清磷显著下降；到2周结束时，唾液磷较基线下降了55%（从73.21±19.19降至33.19±6.53；P<0.00001），血清磷较基线下降了31%（从7.60±0.91降至5.25±0.89mg/dl；P<0.00001）。停止咀嚼口香糖后，唾液磷在第15天恢复到基线水平，而血清磷水平则需要30天恢复到基线。甲状旁腺激素和血清钙浓度不受口香糖影响。总之，在传统磷结合剂基础上增加唾液磷结合可能是改善HD患者高磷血症治疗的一种有效方法。
