FGF23 and Cardiovascular Disease in CKD

描述(申请人提供)：磷和维生素D代谢紊乱是心血管疾病(CVD)和慢性肾脏疾病(CKD)患者死亡的新风险因素，CKD是一种公共卫生流行病，估计影响美国2000万人。成纤维细胞生长因子-23(成纤维细胞生长因子-23)是一种新近发现的调节血磷和1，25-二羟基维生素D(1，25D)水平的激素。成纤维细胞生长因子-23过多最常见的疾病是慢性肾脏病，在肾单位质量下降的情况下，进行性的、严重的升高有助于维持正常的磷酸盐血症。来自我们小组的初步数据表明，正常血磷的CKD患者血清中高水平的成纤维细胞生长因子-23也与冠状动脉钙化、左室肥厚和死亡率有关。重要的是，在高磷血症发生之前很久，成纤维细胞生长因子-23的水平就会升高，并且可以通过常规的临床干预措施，如限制饮食和磷结合剂来降低。因此，我们假设成纤维细胞生长因子-23过量是CKD不良结局的一个可改变的危险因素，并且是一个新的生物标记物，有助于指导目前未接受治疗的正常血磷CKD患者的磷酸盐减少策略。我们经验丰富的研究团队将研究成纤维细胞生长因子-23过量是慢性肾功能不全队列中心血管和肾脏不良结局的新风险因素，这是一项由美国国立卫生研究院支持的针对3800名透析前CKD患者的前瞻性研究，其中绝大多数患者的血磷水平正常。这一结果可能表明临床实践的一个重大范式转变，具有公共卫生意义：更多的人在CKD过程中更早地采取减少磷酸盐的策略。

DESCRIPTION (provided by applicant): Disordered phosphorus and vitamin D metabolism are novel risk factors for cardiovascular disease (CVD) and mortality in patients with chronic kidney disease (CKD), a public health epidemic estimated to affect 20 million people in the US. Fibroblast growth factor-23 (FGF-23) is a recently discovered hormone that regulates serum phosphate and 1, 25-dihydroxyvitamin D (1,25D) levels. The most common disorder of FGF-23 excess is CKD in which progressive, severe increases help maintain normophosphatemia despite declining nephron mass. Preliminary data from our group suggest that increased FGF-23 levels in normophosphatemic CKD patients are also associated with coronary artery calcification, left ventricular hypertrophy, and mortality. Importantly, FGF-23 levels rise long before hyperphosphatemia first develops and can be lowered with routine clinical interventions such as dietary phosphorus restriction and phosphorus binders. Thus, we hypothesize that FGF-23 excess is a modifiable risk factor for adverse outcomes in CKD and a novel biomarker to help guide phosphate reduction strategies in normophosphatemic CKD patients who are not currently treated. Our experienced investigative team will study FGF-23 excess as a novel risk factor for adverse cardiovascular and renal outcomes in the Chronic Renal Insufficiency Cohort, an NIH-supported prospective study of 3800 predialysis CKD patients, the vast majority of whom have normal serum phosphate levels. The results could suggest a major paradigm shift for clinical practice with public health implications: phosphate reduction strategies for far more people far earlier in their course of CKD.