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Mentored patient-oriented research of novel mechanisms for cardiovascular disease in patients with chronic kidney disease

指导以患者为中心的慢性肾病患者心血管疾病新机制的研究

基本信息

批准号：
10544535
负责人：
Tamara Isakova
金额：
$ 11.55万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10544535
关键词：
Address Adverse event Ancillary Study Animals Area Arrhythmia Atrial Fibrillation Bile Acids Biological Markers Calcitriol Calcium Cardiovascular Diseases Cardiovascular system Cause of Death Chronic Kidney Failure Chronic Kidney Insufficiency Clinical Clinical Trials Cohort Studies Collaborations Complication Data Deoxycholic Acid Development Diagnostic tests Diet Dietary Component Disease Disease Outcome Evaluation Event Excretory function Faculty Fatty acid glycerol esters Femur Fibroblast Growth Factor Food Frequencies Funding Future Health Heart failure Homeostasis Image Individual Intake Intervention Intervention Studies Investigation Kidney Knowledge Laboratories Leadership Left Ventricular Hypertrophy Left Ventricular Mass Left ventricular structure Magnetic Resonance Imaging Measurement Measures Medial Medical Students Medicine Mentors Metabolism Midcareer Investigator Award in Patient-Oriented Research Minerals Modeling Multi-Institutional Clinical Trial Myocardial Nephrology Niacinamide Observational Study PTH gene Pathogenesis Patient Care Patients Physiologic pulse Placebos Plasma Production Proteins Public Health Questionnaires Randomized Research Research Infrastructure Research Personnel Research Support Research Training Risk Risk Factors Sampling Series Serum Smooth Muscle Myocytes Sodium Subgroup Testing Therapeutic Time Training United States National Institutes of Health Universities Vascular Smooth Muscle Vascular calcification Work absorption adjudication calcification cardiac magnetic resonance imaging cardiovascular risk factor clinical care clinical investigation cohort coronary artery calcification design diagnostic tool dietary disease phenotype double-blind placebo controlled trial endoplasmic reticulum stress epidemiology study experimental study fibroblast growth factor 23 follow-up gut dysbiosis high risk population improved improved outcome indexing inorganic phosphate intervention effect lanthanum carbonate medical schools mid-career faculty mortality mortality risk novel novel diagnostics novel strategies patient oriented research prevent programs protein intake research study response skills urinary

项目摘要

PROJECT SUMMARY Tamara Isakova, MD, MMSc is applying for the K24 Midcareer Investigator Award in Patient-Oriented Research (POR). She is an Associate Professor of Medicine in the Division of Nephrology at the Northwestern University Feinberg School of Medicine. She directs the Center for Translational Metabolism and Health within the Institute for Public Health and Medicine and the Clinical and Translational Core of the O'Brien Kidney Core Research Center. Dr. Isakova's research is focused on developing the evidence for novel approaches to improve cardiovascular disease outcomes in patients with chronic kidney disease (CKD). She has expertise in epidemiologic studies, POR and multi-center clinical trials, and she has served as a scientific mentor for medical students, residents, fellows, and junior faculty. Support from the K24 will provide Dr. Isakova with protected time 1) to devote more time to mentoring a diverse group of young investigators in POR; 2) to improve her POR mentoring skills through mentor training and guidance from senior mentors; 3) to expand into new scientific areas through cross-disciplinary collaborations; 4) to replenish support for her research program through new NIH funding; and 5) to increase involvement in clinical trials, which will allow her to assume leadership in collaborative POR. A large body of evidence implicates disordered mineral metabolism as a mechanistic contributor to the pathogenesis of cardiovascular disease in CKD. The current proposal builds upon this scientific premise and extends the R01-supported work of the PI. Project 1 leverages ongoing work in the CKD Optimal Management with BInders and NicotinamidE (COMBINE) trial, which is a multi-center, randomized, double-blinded, placebo-controlled trial that tested the hypothesis that nicotinamide (blocks active phosphate transport in the gut) and lanthanum carbonate (phosphate binder) would safely lower serum phosphate and fibroblast growth factor (FGF23) levels compared to placebo over 12 months in 205 patients with CKD stages 3b–4. With support from the K24, the PI will ascertain whether the efficacy of lanthanum carbonate was more pronounced in certain subgroups, determine the relationship of phosphate and FGF23 lowering with myocardial strain, and investigate the effects of interventions on downstream products of nicotinamide and other metabolites and on T50, a calcification biomarker. Project 2 leverages ongoing work in the Chronic Renal Insufficiency Cohort (CRIC) Study, which is an observational study of ~4,000 patients with CKD stages 2 – 4. With support from the K24, the PI will determine whether a combined assessment of T50 and other intermediate cardiovascular disease end-points could help identify a CKD-specific cardiovascular disease phenotype, and she will examine possible modifiable determinants of deoxycholic acid, a secondary bile acid implicated in the pathogenesis of vascular calcification in CKD. Conduct of the proposed Aims will advance the field of non-traditional risk factors for cardiovascular disease, suggest potential therapeutic approaches that the PI will test in future interventional studies and will provide a fertile ground for POR training.

项目总结