FGF-23 Regulation in Chronic Kidney Disease

描述（由申请人提供）： 骨骼疾病在患有慢性肾脏病（CKD）的儿科患者中很常见，并导致不良结局，如生长不良、骨痛和骨折。此外，心血管疾病是CKD儿童和成人死亡的主要原因，而骨骼和心血管疾病似乎在这一人群中存在联系。目前，钙、磷、PTH和维生素D代谢被用于监测骨骼疾病并指导其治疗。然而，纠正这些因素可以改善但不能治愈CKD的骨和血管病变。成纤维细胞生长因子23（FGF-23）是一种新发现的蛋白质，在患有骨病和矿物质离子稳态紊乱的肾功能正常的个体和动物中发现。在CKD患者中也发现了高水平的蛋白质，这些高水平与死亡率增加有关。FGF-23在骨骼中产生，随着CKD的进展，FGF-23的水平升高;然而，CKD患者中FGF-23的调节尚不清楚。因此，本研究将评价： 1)CKD 2 - 4期患者FGF-23对磷酸盐结合剂治疗的反应 2)2 - 4期CKD患者FGF-23和其他参与骨骼矿化的因子的骨表达 将通过评价接受磷酸盐结合剂治疗的2 - 4期CKD患者队列中FGF-23相对于口服磷酸盐负荷的变化来研究这些特定目标。FGF-23和骨骼矿化之间的关系将通过对接受骨活检的CKD患者的骨进行免疫组织化学评价来评估。 公共卫生相关性：一种新的蛋白质FGF-23可能导致与慢性肾脏病（CKD）相关的骨骼和心血管疾病。然而，CKD患者中FGF-23的调节尚不清楚。本研究将研究FGF-23在CKD儿童和年轻成人中的调节方式。了解其病理生理学可能最终导致新的治疗算法，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.