Patient Oriented Studies of Vitamin D in Chronic Kidney Disease

维生素 D 在慢性肾脏病中的以患者为导向的研究

• 批准号: 9026599
• 负责人: RAVI THADHANI
• 金额: $ 10.92万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-15 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9026599
• 关键词: Address; Back; Benefits and Risks; Biological; Biological Markers; Biology; Blood specimen; Bone Diseases; Canada; Cardiac; Cardiac Myocytes; Cardiovascular Diseases; Cause of Death; Chronic; Chronic Kidney Failure; Clinical Research; Data Set; Diabetes Mellitus; Dialysis patients; Dialysis procedure; Disease; Disease Progression; Dose; Educational process of instructing; End stage renal failure; Ergocalciferols; Escherichia coli; Funding; Funding Agency; Gene Expression; Generations; Goals; Grant; Health; Heart Hypertrophy; Hemodialysis; Hormones; Hospitalization; Hypercalcemia; Immune response; Individual; Industry; Infection; Inflammation Mediators; Inflammatory; Institutes; Intervention; Kidney Failure; Laboratories; Lead; Left Ventricular Hypertrophy; Left Ventricular Mass; Link; Measures; Mediating; Mentors; Mentorship; Metabolism; Mid-Career Clinical Scientist Award (K24); Molecular Profiling; Morbidity - disease rate; National Institute of Diabetes and Digestive and Kidney Diseases; Nephrology; New England; Nutritional; Patients; Placebos; Plasma; Population; Population Characteristics; Public Health; Qualifying; Regimen; Research; Research Personnel; Risk Factors; Safety; Scientist; Single Nucleotide Polymorphism; Slice; Staging; Students; Supplementation; Testing; Time; Toxic effect; Training; United States National Institutes of Health; Vitamin D; Vitamin D Analog; Vitamin D Deficiency; Vitamin D supplementation; Vitamin D3 Receptor; Vitamins; base; capsule; cardiovascular disorder risk; cardiovascular infection; cardiovascular visualization; career; cathelicidin; clinically relevant; cohort; coronary artery calcification; cytokine; fibroblast growth factor 23; follow-up; improved; indexing; inorganic phosphate; macrophage; mortality; paricalcitol; patient oriented; patient oriented research; personalized diagnostics; programs; prospective; randomized trial; response; skills; translational study; treatment duration; treatment response

DESCRIPTION (provided by applicant): Vitamin D deficiency is highly prevalent in patients with advanced chronic kidney disease (CKD). Cardiovascular disease (CVD) and infection are the top causes of morbidity and mortality in CKD and end- stage renal disease (ESRD). Evidence generated by the candidate's (Ravi Thadhani, MD, MPH) laboratory has linked CVD progression and altered immune response to inadequate vitamin D levels in CKD/ESRD. Under Dr. Thadhani's direction, a comprehensive patient-oriented research program seeks to investigate the relationship between vitamin D biology and supplementation strategies in terms of mechanistic and clinically relevant endpoints. This application describes three unique aims in three studies (each backed by separate funding sources) that will be pursued by the candidate and his trainees: (1) in DIVINE - an NIH sponsored trial of nutritional vitamin D - his team will determine whether nutritional vitamin D deficiency in ESRD patients leads to altered macrophage function and ex-vivo response to infection; (2) in PRIMO - an industry sponsored trial of active vitamin D and left ventricular hypertrophy [LVH], diastolic function, and cardiac hospitalization in patients with stage 3/4 CKD - his team will determine if baseline levels of 25-hydroxy vitamin D (25D) and fibroblast growth factor-23 (FGF-23) are linked to progression or lack of regression of LVH; and (3) in LUCID - a prospective cohort of incident ESRD subjects supported by the Canadian Institutes of Health - his team will examine whether active vitamin D leads to excess coronary artery calcification. By supporting the candidate's request for this K24 award, important patient-oriented questions will be addressed. Moreover, Dr. Thadhani, with an exemplary record of mentorship, teaching and research, will be afforded the necessary protected time to mentor individuals who comprise a new generation of clinical research fellows and students in Nephrology.

描述（由申请人提供）：在晚期慢性肾脏疾病（CKD）患者中，维生素D缺乏症非常普遍。心血管疾病（CVD）和感染是CKD和末期肾脏疾病（ESRD）发病率和死亡率的主要原因。候选人（Ravi Thadhani，MD，MPH）实验室产生的证据已将CVD的进展和免疫反应改变与CKD/ESRD中维生素D水平不足有关。在Thadhani博士的指导下，一项全面的以患者为导向的研究计划旨在根据机械和临床相关的终点来研究维生素D生物学与补充策略之间的关系。 This application describes three unique aims in three studies (each backed by separate funding sources) that will be pursued by the candidate and his trainees: (1) in DIVINE - an NIH sponsored trial of nutritional vitamin D - his team will determine whether nutritional vitamin D deficiency in ESRD patients leads to altered macrophage function and ex-vivo response to infection; （2）在Primo中 - 一项行业赞助的活性维生素D和左心室肥大[LVH]，舒张功能和心脏住院3/4 CKD的患者 - 他的团队将确定25-羟基维生素D（25D）和成纤维细胞生长因子-23（FGF-23）是否链接或缺乏链接的基线水平（25D）和成纤维细胞生长因子 - （3）在Lucid中 - 由加拿大卫生研究院支持的事件的前瞻性ESRD受试者 - 他的团队将检查活跃的维生素D是否导致过量的冠状动脉钙化。通过支持候选人对这一K24奖的要求，将解决重要的面向患者的问题。此外，Thadhani博士拥有指导，教学和研究的典范记录，将为您提供必要的受保护时间，以指导组成新一代临床研究研究员和肾脏学的学生。

项目成果

Statin use and calcific uremic arteriolopathy: a matched case-control study.

• DOI: 10.1159/000348806
• 发表时间: 2013
• 期刊: American journal of nephrology
• 影响因子: 4.2
• 作者: Nigwekar SU;Bhan I;Turchin A;Skentzos SC;Hajhosseiny R;Steele D;Nazarian RM;Wenger J;Parikh S;Karumanchi A;Thadhani R
• 通讯作者: Thadhani R

Fibroblast growth factor-23 and outcomes: new answers, new questions.

成纤维细胞生长因子 23 和结果：新答案，新问题。

• DOI: 10.1681/asn.2013020169
• 发表时间: 2013
• 期刊: Journal of the American Society of Nephrology : JASN
• 作者: Bhan,Ishir;Thadhani,Ravi
• 通讯作者: Thadhani,Ravi

The Effects of Parenteral Amino Acid Therapy on Protein Carbamylation in Maintenance Hemodialysis Patients.

肠外氨基酸治疗对维持性血液透析患者蛋白质氨甲酰化的影响。

• DOI: 10.1053/j.jrn.2015.01.019
• 发表时间: 2015
• 期刊: Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation
• 作者: Kalim,Sahir;Ortiz,Guillermo;Trottier,CaitlinA;Deferio,JosephJ;Karumanchi,SAnanth;Thadhani,RaviI;Berg,AndersH
• 通讯作者: Berg,AndersH

Reply to "The role of fibroblast growth factor-23 in left atrial volume".

回复“成纤维细胞生长因子23对左心房容积的作用”。

• DOI: 10.1016/j.ahj.2013.02.023
• 发表时间: 2013
• 期刊: American heart journal
• 影响因子: 4.8
• 作者: Tamez,Hector;Andress,Dennis;Solomon,ScottD;Thadhani,Ravi
• 通讯作者: Thadhani,Ravi

Calciphylaxis: risk factors, diagnosis, and treatment.

• DOI: 10.1053/j.ajkd.2015.01.034
• 发表时间: 2015-07
• 期刊: American journal of kidney diseases : the official journal of the National Kidney Foundation
• 作者: Nigwekar SU;Kroshinsky D;Nazarian RM;Goverman J;Malhotra R;Jackson VA;Kamdar MM;Steele DJ;Thadhani RI
• 通讯作者: Thadhani RI