MRI Risk Classification in Children and Young Adults with ADPKD

ADPKD 儿童和年轻人的 MRI 风险分类

• 批准号: 10673378
• 负责人: ARLENE B CHAPMAN
• 金额: $ 10万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2024-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10673378
• 关键词: 14 year old; 15 year old; Adult; Affect; Age; Age-Years; Agreement; Area; Autosomal Dominant Polycystic Kidney; Biological Markers; Body Surface Area; Caring; Chicago; Child; Childhood; Classification; Clinic; Clinical; Clinical Trials; Conflict (Psychology); Coupled; Cyst; Data; Decision Making; Development; Disease; Disease Progression; Distress; Early identification; End stage renal failure; Enrollment; FDA approved; Family; Fingerprint; Future; Gender; Generations; Genes; Genetic; Genotype; Glomerular Filtration Rate; Goals; Growth; Height; Image; Imaging Techniques; Individual; Insurance; Intervention Studies; Kidney; Kidney Diseases; Life Expectancy; MRI Scans; Magnetic Resonance; Magnetic Resonance Imaging; Measurement; Measures; Methods; Modeling; Mutation; Onset of illness; Parents; Patients; Polycystic Kidney Diseases; Predictive Value; Publishing; Radiology Specialty; Renal function; Reporting; Reproducibility; Risk; Risk Assessment; Severities; Severity of illness; Standardization; Texture; Time; Universities; Validation; Visit; Work; age group; age related; base; body volume; clinical care; clinical imaging; disorder risk; early screening; effective therapy; follow-up; high risk; imaging biomarker; imaging modality; improved; kidney imaging; kidney preservation; life-sustaining therapy; lifetime risk; novel; novel therapeutics; offspring; preservation; psychosocial; radiomics; rate of change; recruit; risk stratification; screening; serial imaging; therapy development; tolvaptan; treatment response; young adult

PROJECT SUMMARY Autosomal dominant polycystic kidney disease (ADPKD) accounts for 10% of end stage kidney disease (ESKD) in those <65 years of age. Through a major effort of the Consortium for Radiologic studies in Polycystic Kidney Disease (CRISP) and others, the US FDA has approved the use of tolvaptan to limit kidney disease progression in adult ADPKD patients, and additional clinical trials of other novel therapies are currently underway. A key step in the development of these therapies has been the validation of height-corrected total kidney volume (htTKV) obtained from magnetic resonance imaging (MRI) as a biomarker for identifying subjects at high risk for progression, and htTKV is now used to as a key metric to assess an individual’s lifetime risk for kidney disease progression though the Mayo Imaging Classification (MIC) schema. The development of effective therapies for children and young adults with ADPKD has the potential to limit disease kidney disease progression at an earlier timepoint resulting in increased preservation of kidney function and ultimately a longer life expectancy. Unfortunately, screening asymptomatic children (<18 years) with an affected ADPKD parent is not currently recommended, so even affected young adults may not know they have the disease. Further, children with ADPKD are generally not included in clinical trials, primarily due to the absence of a validated biomarker for disease progression for ADPKD patients <15 years of age. Therefore, despite the promising developments for adult ADPKD patients, these FDA-approved treatments and multiple ongoing clinical trials are unavailable and/or not implemented for children and many young adults with ADPKD. Our preliminary data suggests that: 1) parent-offspring (ages 15-25 years) MICs are in close agreement, suggesting a potential rationale for earlier screening; and 2) a combination of clinical imaging (TKV standardized to body surface area, TKV/BSA) and rapid, quantitative MR Fingerprinting coupled with radiomics analysis can provide the means to develop a risk stratification assessment for ADPKD children 6-14 years of age. The overall objective of this multi-center proposal (University of Chicago and Cleveland Clinic / Case Western Reserve University) is to improve the clinical care for pediatric and young adult ADPKD patient by: 1) defining the association between the MIC of an ADPKD parent and their affected offspring (age 15-25 years) (Aim 1); and 2) developing an MRI-based risk classification for children <15 years of age (age 6-14 years) that can be used to support future clinical trials in this age group (Aim 2). We will recruit 80 children and young adults with ADPKD and a known affected parent. Clinical, demographic and genetic data will be obtained and subjects will undergo cross sectional (Aim 1) as well longitudinal imaging assessments (Aim 2) for a total of 3 visits over the course of 4 years. Confirmation of our preliminary findings would facilitate early identification of pediatric and young adult ADPKD patients at high risk for rapid kidney disease progression, supporting increased screening, expanded inclusion in ongoing and future clinical trials, and access to life-sustaining therapies at an earlier age.

项目总结 常染色体显性遗传性多囊肾病(ADPKD)占终末期肾病的10% (ESKD)在那些&lt；65岁。通过多囊肿瘤放射学研究联合会的主要努力 肾脏疾病(CRISP)和其他疾病，美国FDA已批准使用托伐普坦限制肾脏疾病 成人ADPKD患者的进展，以及其他新疗法的额外临床试验目前正在进行中 正在进行中。这些疗法发展的关键一步是验证身高校正后的总身高 磁共振成像(MRI)获得的肾脏体积(HtTKV)作为识别受试者的生物标志物 病情进展的风险很高，HTTKV现在被用作评估个人一生风险的关键指标 肾脏疾病进展通过梅奥成像分类(MIC)方案。 为患有ADPKD的儿童和年轻人开发有效的治疗方法有可能限制 疾病肾脏疾病在较早的时间点进展，导致肾功能得到更好的保存 最终会延长预期寿命。不幸的是，筛查无症状儿童(18岁) 目前不推荐受影响的ADPKD父母，因此即使是受影响的年轻人也可能不知道他们有 这种疾病。此外，患有ADPKD的儿童通常不包括在临床试验中，主要是因为 15岁的ADPKD患者缺乏有效的疾病进展生物标志物。因此， 尽管成人ADPKD患者的发展前景看好，但这些FDA批准的治疗方法和多个 正在进行的临床试验无法获得和/或没有在患有ADPKD的儿童和许多年轻人中实施。 我们的初步数据表明：1)亲子代(15-25岁)的小鼠非常接近， 提示早期筛查的潜在理由；以及2)结合临床影像(TKV标准化 体表面积，TKV/BSA)和快速、定量的MR指纹结合放射组学分析可以 为ADPKD 6-14岁儿童制定风险分层评估提供手段。整体而言 该多中心提案的目标(芝加哥大学和克利夫兰诊所/凯斯西储医院 大学)是通过以下方式改善儿童和青壮年ADPKD患者的临床护理：1)定义 ADPKD父母及其患病子女(15-25岁)的最低抑菌浓度相关性(目标1)；以及 2)为15岁(6-14岁)的儿童制定可使用的基于核磁共振的风险分类 支持这一年龄段未来的临床试验(目标2)。我们将招募80名患有ADPKD的儿童和年轻人 以及已知的受影响的父母。将获得临床、人口和基因数据，受试者将接受 横断面(目标1)和纵向成像评估(目标2)，在课程中总共进行3次检查 四年了。确认我们的初步发现将有助于儿童和青少年的早期识别 成人ADPKD患者肾脏疾病快速发展的高风险，支持增加筛查， 扩大纳入正在进行的和未来的临床试验，并在更早的年龄获得维持生命的治疗。