Pereira Luciano, Frazão João M
Institute of Investigation and Innovation in Health, University of Porto, Portugal; INEB - National Institute of Biomedical Engineering, University of Porto, Portugal; Department of Nephrology, São João Hospital Center, Porto, Portugal.
Institute of Investigation and Innovation in Health, University of Porto, Portugal; INEB - National Institute of Biomedical Engineering, University of Porto, Portugal; Department of Nephrology, São João Hospital Center, Porto, Portugal.
Clin Chim Acta. 2020 Sep;508:221-227. doi: 10.1016/j.cca.2020.05.023. Epub 2020 May 15.
Vascular wall calcification (VC) is highly prevalent in patients with chronic kidney disease (CKD). In CKD, VC is more frequent and severe than in the general population and it is associated with increased cardiovascular mortality and morbidity. In the last years, laboratory and clinical evidence have drawn the attention to the relationship between bone disease and VC in CKD patients, leading to the concept of a bone-vessel or bone-vascular axis. It means that disorders of bone volume and bone turnover may influence the risk of VC and ultimately the high risk of cardiovascular mortality. In fact, a higher burden of VC has been associated to low bone volume and low bone turnover in hemodialysis (HD) patients with renal osteodystrophy characterized by histomorphometric evaluation of bone biopsies. The molecular mechanisms underlying the regulation of bone cells and vascular cells in CKD are poorly understood. In this review, we discuss relevant evidence linking bone disorders and VC in CKD and also rising molecular players involved in this bone-vascular axis. Indeed, accumulating data is available for two proposed systems: receptor activator for nuclear factor kB (RANK)/ RANK ligand (RANKL)/osteoprotegerin (OPG) system and inhibitors of Wnt signaling - mainly sclerostin. Although they are promising biochemical markers linking bone formation and bone reabsorption with VC, there is a long way to go as long evidence from laboratory studies is often divergent to the clinical data as will be discussed. Future prospective studies are needed in order to evaluate the role of these biochemical players as useful clinical markers for VC, bone volume and perhaps bone turnover.
血管壁钙化（VC）在慢性肾脏病（CKD）患者中极为普遍。在CKD患者中，VC比普通人群更常见且更严重，并且与心血管死亡率和发病率的增加相关。在过去几年中，实验室和临床证据已将人们的注意力吸引到CKD患者的骨病与VC之间的关系上，从而引出了骨-血管轴的概念。这意味着骨量和骨转换的紊乱可能会影响VC的风险，并最终影响心血管死亡的高风险。事实上，在通过骨活检组织形态计量学评估确定为肾性骨营养不良的血液透析（HD）患者中，较高的VC负荷与低骨量和低骨转换相关。CKD中骨细胞和血管细胞调节的分子机制仍知之甚少。在这篇综述中，我们讨论了将CKD中的骨病与VC联系起来的相关证据，以及参与这个骨-血管轴的新兴分子因素。确实，关于两个提出的系统已有越来越多的数据：核因子κB受体激活剂（RANK）/RANK配体（RANKL）/骨保护素（OPG）系统和Wnt信号通路抑制剂——主要是硬化蛋白。尽管它们是将骨形成和骨吸收与VC联系起来的有前景的生化标志物，但正如将要讨论的那样，由于实验室研究的证据往往与临床数据不一致，所以还有很长的路要走。需要未来的前瞻性研究来评估这些生化因素作为VC、骨量甚至骨转换的有用临床标志物的作用。
