FGF-23 Regulation in Chronic Kidney Disease

描述(由申请人提供)： 骨病在患有慢性肾脏病(CKD)的儿科患者中很常见，并会导致不良后果，如生长不良、骨痛和骨折。此外，心血管疾病是CKD儿童和成人的主要死亡原因，而在这一人群中，骨骼疾病和心血管疾病似乎是相关的。目前，钙、磷、甲状旁腺素和维生素D代谢被用来监测骨病并指导其治疗。然而，纠正这些因素可以改善CKD的骨和血管病变，但不能治愈。一种新发现的蛋白质，成纤维细胞生长因子23(成纤维细胞生长因子23)，已经在患有骨病和矿物质离子动态平衡紊乱的肾功能正常的个体和动物中被发现。在慢性肾脏病患者中也发现了高水平的蛋白质，这些高水平的蛋白质与死亡率的增加有关。成纤维细胞生长因子-23在骨骼中产生，水平随着慢性肾脏病的进展而升高；然而，在慢性肾脏病患者中，成纤维细胞生长因子-23的调节尚不清楚。因此，本研究将评估： 1)慢性肾脏病2-4期成纤维细胞生长因子-23对磷酸盐粘结剂治疗的反应 2)CKD 2~4期患者骨组织中成纤维细胞生长因子-23等骨矿化相关因子的表达 这些特定的目的将通过评估接受磷酸盐结合剂治疗的CKD 2-4期患者口服磷酸盐负荷时成纤维细胞生长因子-23的变化来进行研究。通过对接受骨活检的慢性肾脏病患者进行骨组织免疫组织化学评估，将评估成纤维细胞生长因子-23与骨骼矿化的关系。 公共卫生相关性：一种新的蛋白质，成纤维细胞生长因子-23，可能有助于与慢性肾脏疾病(CKD)相关的骨骼和心血管疾病。然而，成纤维细胞生长因子-23在慢性肾脏病患者中的调控尚不清楚。这项研究将研究在患有慢性肾脏病的儿童和年轻人中，成纤维细胞生长因子-23是如何被调节的。对其病理生理学的了解可能最终导致新的治疗算法，以降低发病率和死亡率。

DESCRIPTION (provided by applicant): Bone disease is prevalent in pediatric patients with chronic kidney disease (CKD) and leads to adverse outcomes such as poor growth, bone pain, and fractures. Furthermore, cardiovascular disease is the leading cause of death in children and adults with CKD while bone and cardiovascular disease appear to be linked in this population. Currently, calcium, phosphorus, PTH, and vitamin D metabolism are used to monitor bone disease and guide its treatment. However, correction of these factors ameliorates, but does not cure, bone and vascular lesions in CKD. A newly described protein, fibroblast growth factor 23 (FGF- 23), has been identified in individuals and animals with normal kidney function who have bone disease and disordered mineral ion homeostasis. High levels of the protein are also found in individuals with CKD and these high levels have been linked to an increased mortality rate. FGF-23 is made in bone and levels rise as CKD progresses; the regulation of FGF-23 in individuals with CKD is, however, unknown. Thus, this study will evaluate: 1) The response of FGF-23 to phosphate binder therapy in CKD stages 2-4 CKD 2) The bone expression of FGF-23 and other factors involved in skeletal mineralization in patients with CKD stages 2-4 These specific aims will be investigated by evaluating changes in FGF-23 to oral phosphate load in a cohort of patients with CKD stages 2-4 who are treated with phosphate binding agents. The relationship between FGF-23 and skeletal mineralization will be assessed by immunohistochemical evaluation of bone in patients with CKD who undergo bone biopsy. PUBLIC HEALTH RELEVANCE: A new protein, FGF-23, may contribute to bone and cardiovascular disease associated with chronic kidney disease (CKD). However, the regulation of FGF-23 in patients with CKD is unknown. This study will examine how FGF-23 is regulated in children and young adults with CKD. An understanding of its pathophysiology may ultimately lead to new treatment algorithisms that decrease morbidity and mortality.