Connections between vascular calcification and progression of chronic kidney disease: therapeutic alternatives.
Connections between vascular calcification and progression of chronic kidney disease: therapeutic alternatives.
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血管钙化与慢性肾病进展之间的联系：治疗选择。
DOI：
10.1111/j.1523-1755.2005.09926.x
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Lund,RichardJ
中科院分区：
文献类型：
--
作者：
Hruska,KeithA;Mathew,Suresh;Davies,MatthewR;Lund,RichardJ
血管钙化与慢性肾脏疾病进展之间的联系：治疗方案我们已经表明，肾损伤和慢性肾脏疾病（CKD）直接抑制骨骼合成代谢，刺激骨形成降低血清磷酸盐。最近，在喂食高脂肪/胆固醇饮食的低密度脂蛋白受体缺失小鼠（代谢综合征模型（高血压、肥胖、血脂异常和胰岛素抵抗））中重新发现了这些观察结果。我们已经证明这些小鼠具有内膜动脉粥样硬化型和内侧型血管钙化（VC）。我们已经证明CKD使VC恶化，骨形态发生蛋白-7 （BMP-7）改善VC。发现高脂肪喂养的低密度脂蛋白受体无CKD的动物有高磷血症，使我们检查这些小鼠的骨骼。我们发现骨形成率显著降低，与VC增加和叠加CKD导致的动态骨障碍（ABD）相关，而VC恶化和高磷血症持续存在。通过无骨骼作用的磷酸盐结合剂直接降低血清磷酸盐的部分有效性证明了异常骨矿化与VC之间的病理联系。BMP-7治疗纠正了ABD和高磷血症，与BMP-7驱动的骨骼磷酸盐沉积刺激相容，减少了血浆磷酸盐，从而消除了对VC的主要刺激。因此，在CKD代谢综合征中，成骨细胞成骨潜能的降低导致ABD产生高磷血症和VC，骨骼合成代谢剂BMP-7改善了这一过程，部分是通过增加骨形成和骨骼中磷酸盐的沉积，部分是通过直接作用于血管平滑肌细胞。我们已经证明，导致血管钙化的过程甚至始于轻度肾损伤，然后才出现明显的高磷血症，这是可以预防和治疗的。因此，早期干预CKD是必要的，并可能影响疾病的死亡率。
Connections between vascular calcification and progression of chronic kidney disease: Therapeutic alternativesWe have shown that renal injury and chronic kidney disease (CKD) directly inhibit skeletal anabolism, and that stimulation of bone formation decreases the serum phosphate. Most recently, these observations were rediscovered in low-density lipoprotein receptor null mice fed high-fat/cholesterol diets, a model of the metabolic syndrome (hypertension, obesity, dyslipidemia, and insulin resistance). We had demonstrated that these mice have vascular calcification (VC) of both the intimal atherosclerotic type and medial type. We have shown that VC is worsened by CKD and ameliorated by bone morphogenetic protein -7 (BMP-7). The finding that high-fat-fed low-density lipoprotein receptor null animals without CKD have hyperphosphatemia led us to examine the skeletons of these mice. We found significant reductions in bone formation rates, associated with increased VC and superimposing CKD results in the adynamic bone disorder (ABD), while VC was worsened and hyperphosphatemia persisted. A pathological link between abnormal bone mineralization and VC through the serum phosphorus was demonstrated by the partial effectiveness of directly reducing the serum phosphate by a phosphate binder that had no skeletal action. BMP-7 treatment corrected the ABD and corrected hyperphosphatemia, compatible with BMP-7–driven stimulation of skeletal phosphate deposition reducing plasma phosphate and thereby removing a major stimulus to VC.Thus, in the metabolic syndrome with CKD, a reduction in bone-forming potential of osteogenic cells leads to ABD producing hyperphosphatemia and VC, processes ameliorated by the skeletal anabolic agent BMP-7, in part through increased bone formation and skeletal deposition of phosphate, and in part through direct actions on vascular smooth muscle cells. We have demonstrated that the processes leading to vascular calcification begin with even mild levels of renal injury before demonstrable hyperphosphatemia, and they are preventable and treatable. Therefore, early intervention in CKD is warranted and may affect mortality of the disease.
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相对甲状旁腺功能减退症和动力性骨病。
DOI：
10.1016/s0002-9629(15)40554-3
发表时间：
1999
期刊：
The American journal of the medical sciences
影响因子：
--
作者：
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通讯作者：
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作者：
Sanchez,CP;Kuizon,BD;Abdella,PA;Jüppner,H;Salusky,IB;Goodman,WG
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Goodman,WG
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作者：
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影响因子：
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作者：
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