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

项目摘要/摘要 在这项提案中，我们将利用我们实验室在美国国立卫生研究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、 儿童慢性肾脏疾病的常规诊断试验和特异性肾脏生物标志物试验 (CKiD)研究。明尼苏达大学高级研究和诊断实验室(ARDL)已经 成为临床试验测试值得信赖的资源。在这里，我们强调我们有能力执行准确和 用LC-MS/MS(LC-MS/MS)精确测定碘海醇 以金标准测定CKiD受试者的肾小球滤过率(MGFR)。这和 常规诊断试验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研究人员之前开发了CKiD Under 25(U25)方程式来估计GFR(EGFR)，因为 成年人的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 14-17岁青少年接受CKiD ioheol mGFR方案的标本通过新的 招募以更好地验证并可能改进U25 EGFR公式的准确性。我们是 假设当将更大的儿科人群与mGFR结果合并时 进入U25 EGFR方程，特别是在数据稀疏的新兴成年人口中，准确性 将对U25 EGFR方程进行测试、验证，并可能在U25方程模型中进行改进 需要调整。目标2涉及从健康的年轻成人肾脏获取mGFR结果和样本 M Health Fairview的捐赠者群体来评估U25方程。我们的假设是因为现在的U25 方程最初是从CKD儿童人群中产生的，通过评估年轻的健康患者 这个方程，这项研究将检查U25方程在所有患者中的连续性，或者它将有助于制定新的 在健康和患病的儿科人群中提供更好的GFR估计的模型。最后，目标3盘 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/行为发展和慢性肾脏病进展。我们的假设是生物标志物 例如肌酐和胱抑素C将被输入到U25方程中，并且结果将允许以下CKD 进步。生物标记物T50和FGF23将帮助调查人员评估 受试者≥14岁，患有慢性肾脏病4-5期

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