Vitamin D and Clinical Outcomes in Chronic Hemodialysis Patients

维生素 D 与慢性血液透析患者的临床结果

• 批准号: 7650503
• 负责人: Michel Benjamin Chonchol
• 金额: $ 37.61万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7650503
• 关键词: 1,25 (OH) vitamin D; 25-hydroxyvitamin D; Accounting; Address; Atherosclerosis; Attenuated; Autoimmune Diseases; Biological Assay; Bone Diseases; C-reactive protein; Calcium; Cardiac; Cardiac Death; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cells; Cessation of life; Chronic; Chronic Kidney Failure; Clinical; Clinical Pathways; Clinical Trials; Communicable Diseases; Data; Databases; Death Rate; Diabetes Mellitus; Diagnostic; Dialysis patients; Dialysis procedure; Dose; Enzymes; Epidemic; Event; Figs - dietary; Functional disorder; Future; Goals; Heart Diseases; Heart failure; Hemodialysis; Hormonal; Hospitalization; Hypertension; Hypertrophy; Immune System Diseases; Infection; Inflammation; Inflammatory; Interleukin-6; Kidney; Kidney Diseases; Lead; Link; Measures; Mediating; Mixed Function Oxygenases; Myocardial; Myocardial Infarction; National Institute of Diabetes and Digestive and Kidney Diseases; Natural Immunity; Organ; Outcome; Parathyroid Hormones; Pathogenesis; Patients; Phosphorus; Physiological; Plasma; Population; Predictive Value; Prevalence; Randomized; Relative (related person); Renal Osteodystrophy; Renal Tissue; Research; Research Proposals; Risk Factors; Role; Sampling; Secondary Hyperparathyroidism; Secondary to; Serum; Structural Models; Supplementation; Testing; Therapeutic; Time; Tissues; Upper arm; Vitamin D; Vitamin D Deficiency; Vitamin D3 Receptor; Vitamins; adjudicate; analog; antimicrobial peptide; autocrine; base; cardiovascular disorder risk; cell type; cohort; cytokine; design; epidemiologic data; follow-up; high risk; hormone metabolism; human PTH protein; improved; inflammatory marker; insight; interest; medical complication; mortality; paracrine; primary outcome; public health relevance; secondary outcome; sound; trend

DESCRIPTION (provided by applicant): Cardiovascular diseases (CVD) and infectious diseases are the leading and second causes of death respectively in chronic hemodialysis (HD) patients. Traditional Framingham factors do not appear to sufficiently account for the CVD risks in this population. We therefore propose to explore the role of vitamin D deficiency as a non-traditional CVD risk factor. 25-hydroxyvitamin D (25(OH)D) is converted to the active form, 1,25-dihydroxyvitamin D (1,25(OH)2 D), by the enzyme 1-1-hydroxylase in the kidney. The discoveries that many extra-renal tissues also possess the 1-1-hydroxylase enzyme and vitamin D receptors have provided new insights into the important physiologic autocrine/paracrine roles of vitamin D in various organs, that are dependent on the availability of 25(OH)D from the circulating plasma. Accordingly, epidemiologic data have related 25(OH)D deficiency to CVD and infectious diseases in the non-uremic population. Information in the HD population in this regard is scarce and will constitute the main goal of the present application. We propose to use the stored serum samples and data base from the completed NIDDK-sponsored HEMO Study to examine the relationship between serum vitamin D levels, inflammatory markers and clinical events in chronic HD patients. The objectives of this application are: (1) To measure levels of 25(OH)D, 1,25(OH)2D, Interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs- CRP) in predialysis serum samples collected at baseline and during annual follow-up from chronic HD patients randomized in the HEMO Study. A total of 1228, 1188, 823, 552, 381 and 231 samples collected respectively at the baseline and in follow-up years 1-5 will be assayed (Aim 1). (2) To examine the relationship of serum 25(OH)D levels with cardiac composite outcomes and infectious composite outcomes during follow-up, after statistical adjustment for 1,25(OH)2D and known risk factors for these events (Aim 2 and Aim 3). (3) To examine whether the relationships of cardiac events with lower baseline and follow-up serum 25(OH)D levels are attenuated with statistical adjustment for serum levels of IL-6 and hs-CRP. Positive results of this analysis would suggest that these inflammatory markers are in the causal pathways of the clinical cardiac consequences of 25(OH)D deficiency (Aim 4). Understanding the relationship between serum 25(OH)D levels with clinical outcomes will yield interesting scientific information and have important diagnosti an therapeutic implications for chronic HD patients. PUBLIC HEALTH RELEVANCE: chronic kidney disease is very common in the U.S. but has been generally under-recognized in the last few decades. Patients with advanced kidney disease, especially those requiring chronic hemodialysis, have very high death rates due to heart diseases and infections. The reasons for these high risks are unclear. This research proposal will focus on another epidemic in dialysis patients, namely, vitamin D deficiency, which may be a contributing cause to their heart diseases and infections. Although vitamin D deficiency has long been known to cause bone diseases, evidence is rapidly accumulating in the general U.S. population showing that chronic vitamin D deficiency also causes hypertension, diabetes, myocardial infarction, heart failure, infections and disorder of the immune system, all of which are also very common medical complications in dialysis patients. This application will examine if vitamin D deficiency can indeed be linked to heart diseases and infections in chronic dialysis patients. If the results are positive, it would help to explain why these patients are at such high risks for heart diseases and infections. In addition, it would provide a sound basis for a large clinical trial of vitamin D supplementation to improve the very poor clinical outcomes of dialysis patients.

描述（由申请人提供）：心血管疾病（CVD）和传染病分别是慢性血液透析（HD）患者死亡的主要和第二原因。传统的Framingham因素似乎没有足够说明该人群的CVD风险。因此，我们建议探索维生素D缺乏作为非传统CVD风险因素的作用。 25-羟基维生素D（25（OH）D）通过肾脏中的1-1-羟化酶在肾脏中转化为活性形式，1,25-二羟基维生素D（1,25（OH）2 D）。许多发现，许多肾上腺外组织还具有1-1-羟化酶和维生素D受体的发现，为各种器官中维生素D的重要生理自身分泌/旁分泌作用提供了新的见解，这些生理性自分泌/旁分泌作用依赖于循环等离子体的25（OH）D的可用性。因此，流行病学数据与CVD的25（OH）D缺乏症和非尿毒症人群中的传染病有关。在这方面，高清人群中的信息很少，将构成本应用的主要目标。我们建议使用完整的NIDDK赞助的血液研究中存储的血清样品和数据库来检查慢性HD患者的血清维生素D水平，炎症标记和临床事件之间的关系。该应用的目标是：（1）测量25（OH）D，1,25（OH）2D，白介素-6（IL-6）和高敏感性C反应蛋白（HS-CRP）在基线和在HD HD患者中的年度随访期间收集的综合性血清中的血清血清样品中。将分别在基线和随访年中分别收集1228、1188、823、552、381和231个样本（AIM 1）。 （2）在随访期间，在随访期间，血清25（OH）D水平与心脏复合结果和传染性复合结果的关系，在统计调整为1,25（OH）2D和已知的这些事件风险因素之后（AIM 2和AIM 2）。 （3）检查心脏事件与基线较低和随访血清25（OH）D水平的关系是否受到统计调整，以调整IL-6和HS-CRP的血清水平。该分析的积极结果表明，这些炎症标志物处于25（OH）D缺乏症的临床心脏后果的因果途径中（AIM 4）。了解血清25（OH）D水平与临床结果之间的关系将产生有趣的科学信息，并具有重要的诊断对慢性高清患者的治疗意义。公共卫生相关性：慢性肾脏疾病在美国很常见，但在过去几十年中通常被低估了。患有晚期肾脏疾病的患者，尤其是那些需要慢性血液透析的患者，由于心脏病和感染而导致死亡率很高。这些高风险的原因尚不清楚。该研究建议将重点介绍透析患者的另一种流行病，即维生素D缺乏症，这可能是导致其心脏病和感染的原因。尽管长期以来已知维生素D缺乏症会引起骨骼疾病，但美国普通人群中迅速积累的证据表明，慢性维生素D缺乏症也会引起高血压，糖尿病，心肌梗塞，心力衰竭，感染，感染和免疫系统的疾病，所有这些都是非常常见的疾病患者的医学并发症。该应用将检查维生素D缺乏症是否确实可以与慢性透析患者的心脏病和感染有关。如果结果是阳性的，这将有助于解释为什么这些患者对心脏病和感染的风险如此之高。此外，它将为补充维生素D的大型临床试验提供合理的基础，以改善透析患者的临床结果非常差。