Reduced plasma pyrophosphate levels in hemodialysis patients
Reduced plasma pyrophosphate levels in hemodialysis patients
复制标题
DOI：
10.1681/asn.2004080694
复制
发表时间：
2005-08-01
影响因子：
13.6
通讯作者：
O'Neill, WC
中科院分区：
文献类型：
--
作者：
Lomashvili, KA;Khawandi, W;O'Neill, WC
焦磷酸盐（PPi）是一种已知的羟基磷灰石形成抑制剂，已被证明可以抑制维生素d中毒大鼠的内侧血管钙化。最近的研究表明，内源性PPi的产生可以防止在高浓度钙和磷酸盐中培养的大鼠主动脉的钙化。为了确定血液透析患者的PPi代谢是否改变，我们测量了稳定血液透析患者的血浆水平和PPi的透析清除率。38例临床稳定血透患者透析前血浆[PPi]为2.26 +/- 0.19 μ M， 36例正常患者为3.26 +/- 0.17 μ M （P < 0.01）。大约30%的血浆PPi是蛋白结合的，这在透析患者中没有改变。正常个体与年龄呈弱负相关，透析患者与年龄无明显负相关。透析患者血浆[PPi]与血浆[PO43-]相关（r = 0.56），但与[Ca2+]、甲状旁腺激素或透析剂量无关，并且在透析间期2和3 d之间血浆[PPi]水平没有变化。17例患者在标准血液透析后血浆[PPi]下降32 +/- 5%。2.1 m(2)醋酸纤维素透析器对PPi的体外清除率为36%，5例患者的PPi平均清除率为43 +/- 5 mu mol，与体内清除率相似。清除PPi高于血浆池，但低于估计的细胞外液池。红细胞PPi含量下降24 +/- 4%，表明细胞内PPi也被去除。结论：血液透析患者血浆[PPi]降低，并通过透析清除PPi。一些患者的血浆水平低于先前在培养中被证明可以防止血管钙化的水平，这表明改变的PPi代谢可能有助于血液透析患者的血管钙化。
Pyrophosphate (PPi) is a known inhibitor of hydroxyapatite formation and has been shown to inhibit medial vascular calcification in vitamin D-toxic rats. It was demonstrated recently that endogenous production of PPi prevents calcification of rat aorta that are cultured in high concentrations of calcium and phosphate. For determining whether PPi metabolism is altered in hemodialysis patients, plasma levels and dialytic clearance of PPi were measured in stable hemodialysis patients. Predialysis plasma [PPi] was 2.26 +/- 0.19 mu M in 38 clinically stable hemodialysis patients compared with 3.26 +/- 0.17 in 36 normal subjects (P < 0.01). Approximately 30% of plasma PPi was protein bound, and this was not altered in dialysis patients. There was a weak inverse correlation with age in normal individuals but not in dialysis patients. Plasma [PPi] in dialysis patients was correlated with plasma [PO43-] (r = 0.56) but not with [Ca2+], parathyroid hormone, or the dose of dialysis, and levels did not vary between interdialytic periods of 2 and 3 d. Plasma [PPi] decreased 32 +/- 5% after standard hemodialysis in 17 patients. In vitro clearance of PPi by a 2.1-m(2) cellulose acetate dialyzer was 36%, and the mean PPi removal in five patients was 43 +/- 5 mu mol, consistent with a similar in vivo clearance. Cleared PPi was greater than the plasma pool but less than the estimated extracellular fluid pool. Erythrocyte PPi content decreased 24 +/- 4%, indicating that intracellular PPi is removed as well. It is concluded that plasma [PPi] is reduced in hemodialysis patients and that PPi is cleared by dialysis. Plasma levels in some patients were below those that have previously been shown to prevent calcification of vessels in culture, suggesting that altered PPi metabolism could contribute to vascular calcification in hemodialysis patients.