Vitamin D hormones in CKiD: Prevalence of deficiency and clinical correlates.

描述（由申请人提供）： 这个职业发展奖的目的是成为一个独立的研究者，以患者为导向的研究涉及儿童慢性肾脏病（CKD）。儿童终末期肾病（ESRD）的患病率为86.1/百万。尽管患病率低，但儿童CKD具有显著的发病率和死亡率。0-14岁儿童接受透析治疗的预期剩余寿命只有20年。儿童CKD研究的重点应是确定进展的风险因素。儿童慢性肾病（CKiD）是一项针对1-16岁儿童和青少年肾脏疾病的前瞻性队列研究。这项流行病学研究的目的是确定慢性肾脏疾病进展的危险因素及其对心血管健康、生长和神经认知发育的影响。低维生素D水平最近已成为CKD进展的潜在危险因素，因为它们与高血压和蛋白尿有关。FGF-23是一种新型激素，是1，25二羟基维生素D水平的负调节剂，已被证明与成人ESRD患者的死亡率有关。对于研究提案的初始部分，CKiD研究的数据将用于确定25羟基维生素D（25 OHD）和1，25二羟基维生素D [1，25（OH）2D]缺乏症的患病率和相关性。将制定一份调查问卷，以评估从营养和环境来源摄入的25 OHD。将在NHANES 2001-2004数据库中比较CKiD队列与年龄和种族匹配对照之间25 OHD缺乏症的患病率和相关性。我们建议测量CKiD人群中1，25（OH）2D和FGF-23激素的水平。将确定1，25（OH）2 D与CKD进展和生长延迟的关系。本研究的最后一部分将研究FGF-23的决定因素，并探讨其在维生素D激素轴失调、CKD进展和儿童CKD生长延迟中的作用。我的决心有一个成功的职业生涯研究开始获得硕士学位在公共卫生和K23赠款将进一步帮助我获得必要的技能，以实现我的目标，成为一名独立的临床研究员。 公共卫生相关性：终末期肾病是一种世界性流行病。迫切需要找到新的风险因素，以延迟进展并改善CKD的结局。这项K-23研究提案旨在阐明慢性肾脏疾病进展的新风险因素在最易受这种疾病折磨的人群中的作用。

DESCRIPTION (provided by applicant): The aim of this career development award is to become an independent investigator in patient-oriented research involving children with chronic kidney disease (CKD). The prevalence of pediatric end stage renal disease (ESRD) is 86.1/million. Despite the low prevalence, pediatric CKD carries significant morbidity and mortality. The expected remaining lifetime for a child, 0-14 years of age and on dialysis is only 20 years. The focus of research in pediatric CKD should be identification of risk factors for progression. Chronic Kidney disease in children (CKiD) is a prospective cohort study of kidney disease in children and adolescents aged 1-16 years. The aims of this epidemiologic study are to determine the risk factors for progression of chronic kidney disease and its effects on cardiovascular health, growth and neurocognitive development. Low vitamin D levels have recently emerged as a potential risk factor for CKD progression, because of their association with higher blood pressure and albuminuria.FGF-23 is a novel hormone that is a negative regulator of 1,25 dihydroxy vitamin D levels and has been shown to have an association with mortality in adult ESRD patients. For the initial part of the research proposal, data from the CKiD study will be used to determine the prevalence and correlates of 25 hydroxy vitamin D (25OHD) and 1,25 di hydroxy vitamin D [1,25(OH)2D] deficiency. A questionnaire will be developed to assess the intake of 25OHD from nutritional and environmental sources. Prevalence and correlates of 25OHD deficiency will be compared between the CKiD cohort and age and race matched controls in the NHANES 2001-2004 database. We propose to measure the levels of 1,25 (OH)2D and FGF-23 hormones in the CKiD population. The associations of 1,25 (OH)2 D with the progression of CKD and growth delay will be determined. The last part of our study will examine the determinants of FGF-23 and explore its role in the dysregulation of vitamin D hormone axis, progression of CKD and growth delay in pediatric CKD. My determination to have a successful career in research started with obtaining a Master's degree in Public Health and the K23 grant will further help me to acquire skills necessary to fulfill my aim of becoming an independent clinical investigator. PUBLIC HEALTH RELEVANCE: End stage renal disease is a world wide epidemic. There is an urgent need to find novel risk factors that would delay progression and improve outcomes in CKD. This K-23 study proposal aims to elucidate the role of novel risk factors for chronic kidney disease progression in one of the most vulnerable population to be afflicted by this disease.