Nephrology Division, Universidade de São Paulo, São Paulo, Brazil.
Nephrology Division, Internal Medicine Department, Universidade Federal do Paraná, Curitiba, Brazil.
Kidney Int. 2017 Jun;91(6):1436-1446. doi: 10.1016/j.kint.2016.12.029. Epub 2017 Mar 18.
Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (CKD-MBD) is a complex disease that is not completely understood. However, some factors secreted by the osteocytes might play an important role in its pathophysiology. Therefore, we evaluated the bone expression of proteins in a group of patients with CKD 2-3, CKD 4, and CKD 5 on dialysis and healthy individuals. We also tested several bone remodeling markers, and correlated these levels with bone biopsy findings. As expected, as serum calcium decreased, serum phosphate, alkaline phosphatase, fibroblast growth factor-23 (FGF-23), parathyroid hormone, and osteoprotegerin increased, as CKD progressed. Additionally, there was a gradual increase in bone resorption associated with a decrease in bone formation and impairment in bone mineralization. Bone expression of sclerostin and parathyroid hormone receptor-1 seemed to be increased in earlier stages of CKD, whereas FGF-23 and phosphorylated β-catenin had increased expression in the late stages of CKD, although all these proteins were elevated relative to healthy individuals. Immunohistochemical studies showed that FGF-23 and sclerostin did not co-localize, suggesting that distinct osteocytes produce these proteins. Moreover, there was a good correlation between serum levels and bone expression of FGF-23. Thus, our studies help define the complex mechanism of bone and mineral metabolism in patients with CKD. Linkage of serum markers to bone expression of specific proteins may facilitate our understanding and management of this disease.
慢性肾脏病（CKD）-矿物质和骨异常（CKD-MBD）是一种尚未完全阐明的复杂疾病。然而，破骨细胞分泌的某些因子可能在其病理生理学中发挥重要作用。因此，我们评估了一组 CKD 2-3、CKD 4 和 CKD 5 透析患者和健康个体的骨蛋白表达。我们还测试了几种骨重塑标志物，并将这些水平与骨活检结果相关联。正如预期的那样，随着血清钙的降低，血清磷酸盐、碱性磷酸酶、成纤维细胞生长因子 23（FGF-23）、甲状旁腺激素和护骨素增加，随着 CKD 的进展而增加。此外，与骨形成减少和骨矿化受损相关的骨吸收逐渐增加。在 CKD 的早期阶段，骨硬化素和甲状旁腺激素受体-1 的骨表达似乎增加，而 FGF-23 和磷酸化 β-连环蛋白在 CKD 的晚期表达增加，尽管所有这些蛋白相对于健康个体都升高。免疫组织化学研究表明，FGF-23 和骨硬化素没有共定位，表明不同的破骨细胞产生这些蛋白。此外，血清水平与 FGF-23 的骨表达之间存在良好的相关性。因此，我们的研究有助于确定 CKD 患者骨和矿物质代谢的复杂机制。将血清标志物与特定蛋白质的骨表达联系起来可能有助于我们理解和管理这种疾病。
