FGF23 and Cardiovascular Disease in CKD

描述（由申请方提供）：磷和维生素D代谢紊乱是慢性肾脏疾病（CKD）患者心血管疾病（CVD）和死亡率的新风险因素，慢性肾脏疾病（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（FGF-23）是最近发现的一种调节血清磷酸盐和1，25-二羟维生素D（1，25 D）水平的激素。最常见的FGF-23过量疾病是CKD，其中进行性严重增加有助于维持正常磷酸盐血症，尽管肾单位质量下降。我们小组的初步数据表明，正常血磷CKD患者FGF-23水平升高也与冠状动脉钙化、左心室肥大和死亡率相关。重要的是，FGF-23水平在高磷酸盐血症首次发展之前很久就升高，并且可以通过常规临床干预（如饮食磷限制和磷结合剂）降低。因此，我们假设FGF-23过量是CKD不良结局的一个可改变的风险因素，也是一种新的生物标志物，有助于指导目前未接受治疗的血磷正常的CKD患者的磷酸盐减少策略。我们经验丰富的研究团队将在慢性肾功能不全队列中研究FGF-23过量作为不良心血管和肾脏结局的新风险因素，这是一项由NIH支持的前瞻性研究，涉及3800例透析前CKD患者，其中绝大多数患者血清磷酸盐水平正常。这些结果可能表明临床实践的重大范式转变与公共卫生意义：在CKD病程的早期为更多的人提供磷酸盐减少策略。

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.