The Central Biochemistry Laboratory for the Chronic Kidney Disease in Children Cohort (CKiD)

儿童慢性肾脏病队列中央生物化学实验室 (CKiD)

• 批准号: 10753650
• 负责人: Jesse C Seegmiller
• 金额: $ 32.35万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10753650
• 关键词: 14 year old; 17 year old; Adolescent; Adult; Age; Age Years; Amendment; Behavior; Behavioral; Biochemistry; Biological Markers; Blood; Calibration; Charge; Chemistry; Child; Childhood; Chromatography; Chronic Kidney Failure; Clinical; Clinical Trials; Collection; Complement; Complex; Creatinine; Data; Development; Diagnosis; Diagnostic; Disease; Disease Progression; Diverticulitis; Dryness; Equation; Genitourinary system; Glomerular Filtration Rate; Goals; Health; High Pressure Liquid Chromatography; Individual; Iohexol; Ions; Kidney; Kidney Diseases; Laboratories; Liquid Chromatography; Measurement; Measures; Methods; Minnesota; Modeling; Monitor; Morbidity - disease rate; Neurocognitive; Observational Study; Outcome; Patients; Pediatrics; Plasma; Population; Prevalence; Procedures; Protocols documentation; Public Health; Reflux; Reporting; Research; Research Personnel; Resources; Risk Factors; Routine Diagnostic Tests; Sampling; Serum; Services; Social Development; Specificity; Specimen; Spottings; Testing; Trust; United States; United States National Institutes of Health; Universities; Urethra; Urine; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; clinical practice; cohort; cost; emerging adult; experience; improved; insight; medical specialties; mortality; novel; novel marker; peer; post gamma-globulins; programs; public health relevance; recruit; renal damage; sample collection; social; standard measure; tandem mass spectrometry; young adult

PROJECT SUMMARY/ABSTRACT In this proposal, we will leverage our laboratory’s extensive expertise and experience in National Institutes of Health (NIH) observational studies and provide kit management, specimen management, study management, routine diagnostic testing, and specialty renal biomarker testing for the Chronic Kidney Disease in Children (CKiD) study. The University of Minnesota’s Advanced Research and Diagnostic Laboratory (ARDL) has become a trusted resource for clinical trial testing. Here we emphasize our ability to perform accurate and precise iohexol measurements using liquid chromatography tandem mass spectrometry (LC-MS/MS) to allow for gold standard measured glomerular filtration rate (mGFR) determinations in CKiD subjects. This and routine diagnostic testing is instrumental in understanding the relationships of chronic kidney disease (CKD) to neurocognitive development, behavior development, social development, and cardiovascular disease risk. CKiD investigators previously developed the CKiD under 25 (U25) equation to estimate GFR (eGFR) since adult eGFR equations do not perform well in this young demographic. Our specific aims are (Aim 1) to analyze specimens undergoing the CKiD iohexol mGFR protocol for adolescents in the 14-17 years of age via new recruitment to better validate and possibly improve upon the U25 eGFR equation accuracy. We are approaching this with the hypothesis that when incorporating a larger pediatric population with mGFR results into the U25 eGFR equation, specifically in the emerging adult population where data is sparse, the accuracy of the U25 eGFR equation will be tested, validated, and potentially improved should the U25 equation model need adjustment. Aim 2 involves acquiring mGFR results and specimens from a healthy young adult kidney donor population at M Health Fairview to evaluate the U25 equation. Our hypothesis is since the current U25 equation was primarily generated from a CKD pediatric population, by evaluating young healthy patients with this equation, the study will examine U25 equation continuity in all patients or it will assist in formulating a new model that provides a better estimate of GFR in healthy and diseased pediatric populations. Lastly, Aim 3 sets out to analyze routine and novel biomarkers to assess clinical interpretation and their relation to eGFR, cardiovascular risk, social/behavioral development, and CKD progression. Our hypothesis is that biomarkers such as creatinine and cystatin C will be input into the U25 equation and the results will allow for following CKD progression. Biomarkers T50 and FGF23 will assist investigators in evaluating cardiovascular health in subjects ≥14 years old with CKD at stages 4-5

项目摘要/摘要 在此提案中，我们将利用我们在美国国立国家研究院的广泛专业知识和经验 健康（NIH）观察研究并提供套件管理，标本管理，研究管理， 常规诊断测试和儿童慢性肾脏疾病的专业肾脏生物标志物测试 （CKID）研究。明尼苏达大学的高级研究与诊断实验室（ARDL）已有 成为临床试验测试的值得信赖的资源。在这里，我们强调我们执行准确的能力和 使用液相色谱串联质谱法（LC-MS/MS）进行精确的iohexol测量，以允许 对于金标准测量的肾小球滤过率（MGFR）测定。这个和 常规诊断测试有助于了解慢性肾脏疾病（CKD）与 神经认知发展，行为发展，社会发展和心血管疾病风险。 CKID研究人员以前开发了25（U25）方程的CKID，以估算GFR（EGFR），因为 在这个年轻的人群中，成人EGFR方程表现不佳。我们的具体目标是（目标1）分析 在14-17岁的青少年使用新的CKID iohexol MGFR方案进行的标本通过新 招募以更好地验证U25 EGFR方程的准确性。我们是 以这样的假设接近这一点，即在将较大的小儿种群纳入MGFR结果时 进入U25 EGFR方程，特别是在数据稀疏的新兴成人人群中，准确性 如果U25方程模型，将测试，验证和可能改进的U25 EGFR方程 需要调整。 AIM 2涉及从健康的年轻成人肾脏中获取MGFR结果和标本 M Health Fairview的捐助者人口评估U25方程。我们的假设是因为当前的U25 方程主要是由CKD小儿人群产生的，它通过评估年轻健康患者 该方程式，该研究将检查所有患者的U25方程连续性，否则将有助于制定新的 可更好地估计健康和脱离儿科人群中GFR的模型。最后，目标3套 分析常规和新型生物标志物，以评估临床解释及其与EGFR的关系， 心血管风险，社会/行为发展和CKD进展。我们的假设是生物标志物 例如肌酐和半胱氨酸蛋白酶C将输入U25方程，结果将允许遵循CKD 进展。生物标志物T50和FGF23将帮助调查人员评估心血管健康 受试者在4-5阶段患有CKD的14岁患者