Proteomic Approach to CKD Biomarker Discovery and Validation

CKD 生物标志物发现和验证的蛋白质组学方法

• 批准号: 7800089
• 负责人: JOSEF CORESH
• 金额: $ 85.31万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7800089
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Affect; African American; Albumins; Albuminuria; Antibodies; Arts; Biological Markers; Biometry; Blood; Cardiovascular Diseases; Caring; Case-Control Studies; Cessation of life; Chronic Kidney Failure; Clinical Chemistry; Clinical Trials; Complement; Creatinine; Cystatins; Dialysis procedure; Diet; Discipline; Disease; Disease Progression; End stage renal failure; Endothelin; Enzyme-Linked Immunosorbent Assay; Epidemiology; Event; FABP1 gene; Fibronectins; Filtration; General Population; Genetic; Genomics; Glomerular Filtration Rate; Goals; Health Policy; Individual; Kidney; Knowledge; Mass Spectrum Analysis; Measurement; Measures; Methods; Monitor; Names; National Health and Nutrition Examination Survey; Nephrology; Outcome; Participant; Pathway interactions; Patient Care; Patients; Pilot Projects; Population; Population Study; Principal Investigator; Process; Proteins; Proteinuria; Proteomics; Renal function; Research; Research Design; Research Personnel; Review Literature; Risk; Risk Assessment; STC1 gene; Sample Size; Sampling; Screening procedure; Serum; Serum Markers; Serum Proteins; Severities; Staging; Technology; Testing; Transplantation; Urine; Validation; Vascular Cell Adhesion Molecule-1; clinical care; clinical practice; cohort; design; diabetic patient; experience; follow-up; improved; innovation; insight; member; multiple reaction monitoring; muscle form; non-diabetic; novel; novel marker; numb protein; outcome forecast; population based; post gamma-globulins; public health relevance; response; urinary; verification and validation

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) is common and associated with a wide range of adverse outcomes. Two biomarkers, serum creatinine and albuminuria, provide the mainstay for staging and risk assessment for the majority of CKD patients. Both clinical trials and clinical care are hampered by the limitations of these markers and could benefit substantially from discovery and validation of additional markers. In reponse to the RFA, "CKD Biomarker Discovery and Validation Consortium", we propose an innovative project that combines breakthrough methods for biomarker discovery with rigorous epidemiological, statistical and clinical chemistry expertise applied with a deep knowledge of four extremely well characterized cohorts. Aim 1: Biomarker Discovery. 1 .A. De novo discovery of serum filtration markers for CKD staging. State of the art proteomic discovery methods will identify proteins with >2x elevation from baseline to follow-up in stored serum of AASK participants whose measured GFR declined from >60 to <30 ml/min/1.73m2 or 2x their serum creatinine. 1 .B. Targeted discovery of urine and serum markers of damage for CKD progression. Absolute quantiation mass spectrometry methods will tests 15 of the most promising urine and serum markers in their ability to distinguish 100 cases with rapid CKD progression to EBRD from 100 controls with similar baseline measured GFR which remained stable from the AASK and MDRD Studies. 1 .C. Verification of the most promising markers from 1 .A. and 1 .B in a larger sample size Aim 2: Biomarker Validation: We will test the most promosing biomarkers identified in aim 1 and through by the consortium in their ability to estimate kidney function and risk of CKD progression in the entire AASK and MDRD Study population and case-control studies of progressive CKD in ARIC and a sample of NHANES. Our studies are guided by extensive experience in nephrology, biostatistics, epidemiology, proteomics, clinical chemistry, collaborative studies, recent pilot studies of novel markers for GFR estimation and genomic discoveries of relevant pathways for AKI and CKD. PUBLIC HEALTH RELEVANCE: Chronic kidney disease is common and usually stages by blood and urine markers. Currently serum creatinine and urinary albumin at the most widely used biomarkers for staging and prognosis of patients with chronic kidney disease. We propose to join a consortium whose goal is to discover and validate additional markers which will improve patient care and faciliate research in chronic kidney disease.

描述（由申请人提供）：