Novel Biomarkers of Chronic Kidney Disease in Children

儿童慢性肾脏病的新型生物标志物

• 批准号: 9164754
• 负责人: Jason Henry Greenberg
• 金额: $ 15.58万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-18 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9164754
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Address; Adult; Ancillary Study; Area; Biological Assay; Biological Markers; Biometry; Blood; CCL2 gene; Cardiovascular system; Caregivers; Caring; Child; Child Care; Childhood; Chronic Kidney Failure; Clinical; Clinical Trials; Collaborations; Comorbidity; Creatinine; Data; Development; Dialysis procedure; Discrimination; Disease Progression; Employee Strikes; End stage renal failure; Enrollment; Environment; Etiology; Evaluation; Event; Family; Fibrosis; Functional disorder; Funding; Future; Glomerular Filtration Rate; Goals; Growth and Development function; Healthcare Systems; IL6 gene; Inflammation; Injury; Interleukin-10; Interleukin-18; Intervention; Kidney; LCN2 gene; MMP9 gene; Measures; Mentors; Mentorship; Methodology; Modeling; Morbidity - disease rate; Outcome; Participant; Patients; Pediatrics; Phenotype; Population; Proteinuria; Qualifying; Renal function; Research; Research Training; Resources; Review Literature; Risk; Risk Factors; Sampling; Serum; Statistical Methods; Surrogate Endpoint; TNFRSF1A gene; TNFRSF1B gene; Therapeutic Intervention; Time; Training; Translational Research; Transplantation; Tubular formation; Universities; Urine; Validation; Visit; Writing; base; biomarker panel; clinical care; cohort; disorder risk; effective intervention; follow-up; formal learning; high risk; improved; improved outcome; innovation; mortality; multidisciplinary; novel marker; pediatric patients; predictive modeling; procollagen Type III-N-terminal peptide; programs; prospective; repaired; response; skills; specific biomarkers; statistics; treatment response; urinary

Project Summary. Candidate. I am a pediatric nephrologist at Yale University dedicated to improving outcomes for children with chronic kidney disease (CKD). The goal of my application is to obtain mentored research training to develop a biomarker-augmented risk prediction model of pediatric CKD progression for use in future clinical trials. This research will build upon my prior training, which focused on the risk of CKD after acute kidney injury and the use of biomarkers to predict renal outcomes in children. This proposal will provide me with hands-on learning and formal didactic coursework in advanced statistics, biomarker methodology, and pediatric CKD. I will also intensely focus on developing the professional skills necessary for establishing effective collaborations, scientific writing, and obtaining funding to support my research. To accomplish my stated plan, I have the support of my highly qualified primary co-mentors (Drs. Chirag Parikh and Susan Furth) and mentoring committee (Drs. Haiqun Lin, Eugene Shapiro, and Prasad Devarajan) with interdisciplinary expertise in the fields of kidney injury biomarkers, translational research, biostatistics, and pediatric CKD. This multidisciplinary mentorship along with the highly skilled training environment at Dr. Parikh's, Program of Applied Translational Research will allow me to conduct my proposed research and establish an independently funded research program. Project. Progression of CKD in children leads to end stage renal disease (ESRD), which is associated with mortality rates 30-150 times higher than the general pediatric population. The traditional biomarkers, serum creatinine and proteinuria, are used to predict progression of CKD in clinical trials even though both correlate poorly with the progression of CKD and the response to interventions. There are numerous candidate therapies for CKD, but with a continued reliance on serum creatinine and proteinuria, clinical trials will likely continue to fail. The field of CKD biomarkers in children is a very promising area of research with a small amount of resources invested to date. Predicting progression of CKD will allow clinicians to better time follow-up, referral for transplant, and provide better guidance to families. More importantly, an optimal panel of biomarkers and risk prediction model can replace proteinuria and serum creatinine in biomarker guided clinical trials. We plan to measure urine and serum biomarkers of kidney injury, inflammation, repair, and fibrosis from the baseline samples of the 869 children with CKD enrolled in the CKD in Children (CKiD) cohort and determine their relationship with longitudinal measured GFR decline and incident ESRD. The optimal combination of biomarkers plus clinical variables from 2/3rd's of the CKiD patients will yield a risk prediction model to predict CKD progression. Our risk prediction model will be validated for longitudinal GFR decline, internally in 1/3rd of the CKiD patients, and externally in the 124 children of the Assessment, Serial Evaluation, and Subsequent Sequelae in AKI cohort. Developing a risk prediction model of CKD progression can be paradigm changing, transforming clinical care for children with CKD.

项目摘要。候选人。我是耶鲁大学的儿科肾脏科医生，致力于改善结果 适用于慢性肾脏疾病（CKD）的儿童。我应用的目的是获得指导的研究培训 开发生物标志物增强的风险预测模型的小儿CKD进展用于未来的临床 试验。这项研究将基于我先前的培训，该培训的重点是急性肾脏受伤后CKD的风险 以及使用生物标志物来预测儿童的肾脏结局。该建议将为我提供动手 高级统计，生物标志物方法和小儿CKD的学习和正式教学课程。我会 还专注于建立有效合作所需的专业技能， 科学写作，并获得资金来支持我的研究。为了完成我的既定计划，我得到了支持 我高素质的初级院长（Chirag Parikh和Susan Furth博士）和指导委员会（Drs。 Haiqun Lin，Eugene Shapiro和Prasad Devarajan）具有跨学科的专业知识 生物标志物，翻译研究，生物统计学和小儿CKD。这种多学科的指导以及 Parikh博士的高技能培训环境，应用转化研究计划将使我能够 进行我建议的研究并建立一个独立资助的研究计划。 项目。儿童CKD的进展导致终结阶段肾脏疾病（ESRD），这与 死亡率比普通小儿人群高30-150倍。传统的生物标志物，血清 肌酐和蛋白尿，用于预测临床试验中CKD的进展，尽管两者都相关 CKD的进展和对干预措施的反应很差。有许多候选疗法 对于CKD，但由于持续依赖血清肌酐和蛋白尿，临床试验可能会继续失败。 儿童中CKD生物标志物领域是一个非常有前途的研究领域，少量 迄今为止投资的资源。预测CKD的进展将使临床医生可以更好地随访，转介 移植，并为家庭提供更好的指导。更重要的是，最佳的生物标志物和风险面板 预测模型可以在生物标志物引导的临床试验中替代蛋白尿和血清肌酐。我们计划 测量基线肾脏损伤，炎症，修复和纤维化的尿液和血清生物标志物 在儿童（CKID）队列中注册CKD的869名儿童的样本 与纵向测量的GFR下降和ESRD的关系。生物标志物的最佳组合 再加上来自CKID患者2/3的临床变量将产生风险预测模型，以预测CKD的进展。 我们的风险预测模型将用于纵向GFR下降，内部1/3的CKID患者，以及 在124名评估儿童中，AKI队列中的序列评估和后续后遗症。 开发CKD进展的风险预测模型可以改变范式，从而改变临床护理 患有CKD的孩子。