Precision Allograft Rejection Using Novel Diagnostic Approaches in Kidney Transplantation - Allograft Transcriptomics Landscape Analysis Using Sequencing (the PANDA-Kids-ATLAS Study)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 600
- 试验地点
- 1
- 主要终点
- Identification of Molecular Classifiers for Kidney Allograft Rejection Using Banff Human Organ Transplant (B-HOT) Gene Panel via NanoString nCounter®
研究概览
简要总结
Children with kidney failure have markedly increased mortality and face repeated transplantation over their lifetime due to limited allograft half-life (12-15 years). Current biopsy-based diagnoses of rejection (using Banff 2022 criteria) suffer from variability and limited sensitivity. PANDA-Kids-ATLAS will analyze up to 600 pediatric FFPE kidney biopsies across multiple centres using the Banff Human Organ Transplant (B-HOT) NanoString panel to develop and validate molecular classifiers of AMR, TCMR and related phenotypes. A secure REDCap database will integrate molecular, pathological and clinical data, aiming to improve early detection, personalize therapy, and enhance long-term graft survival and patient quality of life.
详细描述
The study builds a deeply phenotyped international cohort of pediatric transplant patients (<21 years) with both retrospective (2014-present) and prospective (through Dec 2027) biopsy sampling. Four diagnostic "baskets" (classical AMR/TCMR; probable ABMR/MVI; other injury; normal) will each contribute equal numbers of cases for classifier validation (Part A) and real-world prevalence samples for outcome association (Part B). FFPE blocks will be centrally reviewed via Banff 2022 automated and expert pathologist interpretation, then processed by NanoString nCounter® using the 770-gene B-HOT panel. Stratified random sampling, robust QC, and integration with clinical/immunological parameters in REDCap will underpin molecular classifier development and validation. Follow-up includes clinical outcomes and graft function monitoring.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 0 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≤ 21 years
- •Single kidney transplant recipients (deceased or living donor)
- •Written informed consent from patients/guardians
排除标准
- •Multi-organ transplantation history
- •Biopsies with insufficient tissue
结局指标
主要结局
Identification of Molecular Classifiers for Kidney Allograft Rejection Using Banff Human Organ Transplant (B-HOT) Gene Panel via NanoString nCounter®
时间窗: 3 years
Molecular signatures (molecular classifiers) will be identified through bulk transcriptomic analysis utilizing the validated Banff Human Organ Transplant (B-HOT) gene panel, consisting of 770 rejection- and tolerance-related genes. Formalin-fixed, paraffin-embedded (FFPE) biopsy samples from pediatric kidney transplant recipients will be processed and analyzed using the NanoString nCounter® platform. Specifically, molecular classifiers distinguishing classical antibody-mediated rejection (AMR), T-cell mediated rejection (TCMR), and novel Banff 2022 antibody-mediated rejection-related categories-including microvascular inflammation with donor-specific antibodies and negative C4d staining (MVI+DSA-C4d-) and probable antibody-mediated rejection (pABMR)-will be quantified and reported. Classifier results will be summarized as normalized gene expression profiles, enabling clear discrimination among different categories of rejection and non-rejection biopsies.
次要结局
- Integration of Molecular Classifiers with Clinical Parameters into an Archetype-based Diagnostic System for Kidney Allograft Rejection(3 years)
- Integration of Molecular Classifiers with Biological and Immunological Parameters into an Archetype-based Diagnostic System for Kidney Allograft Rejection(3 years)