Vitamin D Catabolism in Chronic Kidney Disease

慢性肾脏病中的维生素 D 分解代谢

• 批准号: 8694877
• 负责人: Ian H de Boer
• 金额: $ 69.94万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8694877
• 关键词: 1,25 (OH) vitamin D; 25-hydroxyvitamin D; Ancillary Study; Animals; Attenuated; Binding; Biochemical; Biological; Biological Assay; Biological Markers; Black race; Calcifediol; Calcitriol; Cardiovascular Diseases; Catabolism; Cessation of life; Cholecalciferol; Chronic Kidney Failure; Chronic Kidney Insufficiency; Clinical; Clinical Treatment; Clinical Trials; Clinical assessments; Data; Dietary Phosphorus; Dihydroxycholecalciferols; Disease Progression; Drug Kinetics; End stage renal failure; Enzymes; Epidemiologic Studies; Ergocalciferols; Evaluation; Event; Fibrosis; Functional disorder; Glomerular Filtration Rate; Goals; Gold; Health; Hormones; Human; Inflammation; Inorganic Sulfates; Intervention; Intervention Studies; Kidney; Label; Mass Spectrum Analysis; Measurement; Mediating; Metabolic; Metabolic Pathway; Metabolism; Morbidity - disease rate; Observational Study; Outcome; Parathyroid gland; Parents; Patients; Persons; Phosphorus; Plasma; Population; Production; Race; Reading; Renin-Angiotensin System; Risk; Risk Factors; Role; Secondary Hyperparathyroidism; Serum; Site; Testing; Tissues; Unspecified or Sulfate Ion Sulfates; Vitamin D; Vitamin D Deficiency; Vitamin D2; Vitamin D3 Receptor; Work; adverse outcome; analog; base; clinical Diagnosis; clinical care; clinical decision-making; cohort; high risk; improved; modifiable risk; mortality; novel; paricalcitol; patient oriented; premature; prevent; racial difference; research clinical testing; research study; response; therapeutic target; tool

DESCRIPTION (provided by applicant): Impaired vitamin D metabolism is a promising therapeutic target to reduce the marked morbidity and mortality of chronic kidney disease (CKD). However, the evaluation and treatment of impaired vitamin D metabolism is currently limited by a lack of effective biomarkers. Our preliminary data suggest that reduced vitamin D catabolism accompanies reduced 1, 25- dihydroxyvitamin D production in CKD and that evaluation of vitamin D catabolism may offer a valuable new tool to guide clinical diagnosis and treatment. We propose to define vitamin D catabolism across glomerular filtration rate and race and test whether a low circulating concentration of 24, 25-dihydroxyvitamin D, the most abundant product of 25-hydroxyvitamin D catabolism by CYP24A1, is a modifiable risk factor for adverse health outcomes in CKD. Gold standard pharmacokinetic studies will define whether and to what extent vitamin D catabolism is impaired in CKD. Synergistic ancillary studies to existing epidemiologic studies and clinical trials will test associations of 24,25-dihydroxyvitamin D concentration with adverse health outcomes, examine the effects of a broad range of common vitamin D-related interventions on circulating 24,25-dihydroxyvitamin D, and explore whether baseline 24,25-dihydroxyvitamin D concentration identifies patients who have biochemical responses to such common interventions. This combination of experiments will comprehensively evaluate vitamin D catabolism in CKD and determine whether 24,25-dihydroxyvitamin D may fill an important void in the clinical assessment of vitamin D metabolism in this population.

描述（由申请方提供）：维生素D代谢受损是降低慢性肾脏疾病（CKD）显著发病率和死亡率的有前景的治疗靶点。然而，维生素D代谢受损的评估和治疗目前受到缺乏有效生物标志物的限制。我们的初步数据表明，维生素D催化剂减少伴随着减少1，25-二羟维生素D的生产在CKD和维生素D催化剂的评价可能提供一个有价值的新工具，以指导临床诊断和治疗。我们建议在肾小球滤过率和种族中定义维生素D催化剂，并测试低循环浓度的24，25-二羟基维生素D（CYP 24 A1最丰富的25-羟基维生素D催化剂产物）是否是CKD不良健康结局的可改变风险因素。金标准药代动力学研究将确定CKD中维生素D催化剂是否受损以及受损程度。现有流行病学研究和临床试验的协同辅助研究将测试24，25-二羟维生素 维生素D浓度与不良健康结果的关系，检查广泛的常见维生素D相关干预措施对循环24，25-二羟维生素D的影响，并探讨基线24，25-二羟维生素D浓度是否可识别对此类常见干预措施有生化反应的患者。这种实验组合将全面评估CKD中的维生素D catalysts，并确定24，25-二羟基维生素D是否可以填补该人群中维生素D代谢临床评估的重要空白。