Spatial Transcriptomics in Kidney Transplantation
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- Kidney biopsy transcriptomic signature
研究概览
简要总结
The study is an investigator-led, prospective, longitudinal, observational cohort study.
The central hypothesis for this study is that spatial data will reveal new insights to immune cell function and local interactions within the kidney tissue to better predict important clinical outcomes. Investigators aspire to establish a prospective, longitudinal cohort to improve the diagnosis and management of kidney transplant rejection using precision pathology.
By utilising new spatial technologies, the investigators aim to:
- Derive a spatially resolved transcriptomic signature of kidney transplant rejection subtypes
- Derive accurate transcriptomic signatures aligned with key cell types within the transplant kidney
- Develop refinements to histological kidney rejection diagnostic and scoring classification
- Correlate of spatial and refined biopsy scoring features to clinically important outcomes
详细描述
Primary outcomes: The correlation of kidney transplant rejection subtypes with transcriptomic, spatial and cell-type features
Secondary outcomes: Correlation of the refined biopsy scoring criteria and transcriptomics signatures with:
- All cause graft loss
- Death censored graft loss
- Treatment resistant rejection
- Delayed graft function (DGF)
- Biopsy evidence of borderline rejection based on current Banff scoring system
- Biopsy proven acute rejection - T-cell mediated (TCMR), antibody-mediated (ABMR), mixed
- Chronic rejection - acute or inactive
- Interstitial fibrosis scores (IFTA) on kidney biopsy on any biopsies
- Chronic transplant glomerulopathy on kidney biopsy on any biopsies
- Development of BK virus associated nephropathy at any time
- Recurrent disease (original cause of kidney failure) post transplantation at any time
- Kidney function with serum creatinine, estimated or measured glomerular filtration rate (GFR)
- Development of albuminuria
- Surrogate end-points - eGFR slope and iBOX(TM) score
- Donor-recipient HLA and non-HLA genomic mismatches
- Recipient proteinomic expression profile
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All participants included in the study must be age ≥ 18 years old at time of enrolment and
- •able to provide informed consent (interpreter permitted) for enrolment
- •consenting to longitudinal follow up (can withdraw post enrolment)
- •consenting to provide samples for biobanking, including blood, urine, faecal and/or kidney biopsy tissue (collected prospectively, separate to routine care)
排除标准
- •Patients will be excluded from the study if they are
- •unable (or unwilling) to provide consent, or
- •have life-expectancy less than 6-months, or
- •have received a haematopoietic stem cell transplant in the past 5 years.
结局指标
主要结局
Kidney biopsy transcriptomic signature
时间窗: At biopsy - based on collected tissue sample
Based on bulk and/or spatial transcriptomic experiments
Kidney biopsy features
时间窗: At biopsy or during study follow up following biopsy during study (expected 12-months)
Based on the pathology subtype at original diagnosis
Kidney cell type composition
时间窗: At biopsy - based on collected tissue sample
Cell type phenotyping of immune and kidney cell types
次要结局
- Treatment resistant rejection(At biopsy or during study follow up after biopsy (expected average 12-months))
- Interstitial fibrosis scores (IFTA)(At biopsy or during study follow up after biopsy (expected average 12-months))
- BK virus associated nephropathy(At biopsy or during study follow up after biopsy (expected average 12-months))
- Proteinomic signature(At biopsy or during study follow up after biopsy (expected average 12-months))
- All cause graft loss(At biopsy or during study follow up after biopsy (expected average over 60-months))
- Biopsy proven acute rejection(At biopsy or during study follow up after biopsy (expected average 12-months))
- Kidney function(At biopsy or during study follow up after biopsy (expected average 12-months))
- Death censored graft loss (DCGL)(At biopsy or during study follow up after biopsy (expected average over 60-months))
- Delayed graft function (DGF)(At biopsy or during study follow up after biopsy (within 7 days of transplantation))
- Surrogate end-points(At biopsy or during study follow up after biopsy (expected average 12-months))
- Biopsy evidence of borderline rejection(At biopsy or during study follow up after biopsy (expected average 12-months))
- Chronic rejection(At biopsy or during study follow up after biopsy (expected average 12-months))
- Albuminuria(At biopsy or during study follow up after biopsy (expected average 12-months))
- Donor to recipient mismatches(At biopsy or during study follow up after biopsy (expected average 12-months))
研究者
Jennifer Li
CPI, Nephrologist and Transplant Physician
Western Sydney Local Health District