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

项目总结/摘要 在本提案中，我们将利用我们实验室在美国国家科学院的广泛专业知识和经验， 健康（NIH）观察性研究，并提供试剂盒管理，标本管理，研究管理， 儿童慢性肾脏病的常规诊断检测和专业肾脏生物标志物检测 （CKiD）研究。明尼苏达大学高级研究和诊断实验室（ARDL） 成为临床试验测试的可靠资源。在这里，我们强调我们的能力，执行准确， 使用液相色谱串联质谱法（LC-MS/MS）进行精确的碘海醇测量， 用于CKiD受试者中测定肾小球滤过率（mGFR）的金标准。这个和 常规诊断测试有助于了解慢性肾病（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研究者先前开发了CKiD 25（U25）方程来估计GFR（eGFR）， 成人eGFR方程在这一年轻人群中表现不佳。我们的具体目标是（目标1）分析 在14-17岁青少年中接受CKiD碘海醇mGFR方案的样本，通过新的 招募，以更好地验证并可能提高U25 eGFR方程的准确性。我们 接近这一假设，当纳入一个更大的儿科人群与mGFR结果 在U25 eGFR方程中，特别是在数据稀少的新兴成年人群中， 将对U25 eGFR方程进行检验、验证，如果U25方程模型 需要调整。目的2涉及从健康的年轻成人肾脏获得mGFR结果和标本 在M Health Fairview的供体人群中评估U25方程。我们的假设是，由于目前的U25 方程主要由CKD儿科人群生成，通过评估年轻健康患者， 该方程，研究将检查所有患者的U25方程连续性，或将有助于制定新的 该模型可更好地估计健康和患病儿科人群的GFR。最后，Aim 3集 分析常规和新的生物标志物，以评估临床解释及其与eGFR的关系， 心血管风险、社会/行为发育和CKD进展。我们的假设是生物标记物 如肌酐和胱抑素C将输入U25方程，结果将允许以下CKD 进展生物标志物T50和FGF 23将帮助研究人员评估心血管健康， 年龄≥14岁的CKD 4-5期受试者

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