Spatial Transcriptomics in Kidney Transplantation
- Conditions
- Transplant ComplicationKidney Injury
- Interventions
- Other: Non interventional
- Registration Number
- NCT06288425
- Lead Sponsor
- Western Sydney Local Health District
- Brief Summary
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
- Detailed Description
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:
1. All cause graft loss
2. Death censored graft loss
3. Treatment resistant rejection
4. Delayed graft function (DGF)
5. Biopsy evidence of borderline rejection based on current Banff scoring system
6. Biopsy proven acute rejection - T-cell mediated (TCMR), antibody-mediated (ABMR), mixed
7. Chronic rejection - acute or inactive
8. Interstitial fibrosis scores (IFTA) on kidney biopsy on any biopsies
9. Chronic transplant glomerulopathy on kidney biopsy on any biopsies
10. Development of BK virus associated nephropathy at any time
11. Recurrent disease (original cause of kidney failure) post transplantation at any time
12. Kidney function with serum creatinine, estimated or measured glomerular filtration rate (GFR)
13. Development of albuminuria
14. Surrogate end-points - eGFR slope and iBOX(TM) score
15. Donor-recipient HLA and non-HLA genomic mismatches
16. Recipient proteinomic expression profile
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 500
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)
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.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Chronic (active) rejection Non interventional Biopsy features of chronic rejection - T-cell, antibody or mixed types BK virus associated nephropathy (BKVAN) Non interventional Biopsy features of SV40 positive staining in tubules to diagnose BKVAN No rejection, normal biopsy (controls) Non interventional Normal biopsy - no acute tubular injury (ATI), rejection or any other pathology Acute kidney injury without evidence of rejection Non interventional Biopsy features of acute tubular injury but no evidence of rejection Subclinical Rejection Non interventional Biopsy features of injury and inflammation but not meeting current diagnostic criteria for acute or chronic rejection Isolated glomerulitis Non interventional Biopsy features of inflammation in the glomeruli only Acute rejection Non interventional Biopsy features of T-cell mediated, antibody-mediated, or mixed rejection Isolated vascular rejection Non interventional Biopsy features of inflammation in the blood vessels only
- Primary Outcome Measures
Name Time Method Kidney biopsy transcriptomic signature At biopsy - based on collected tissue sample Based on bulk and/or spatial transcriptomic experiments
Kidney biopsy features 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 At biopsy - based on collected tissue sample Cell type phenotyping of immune and kidney cell types
- Secondary Outcome Measures
Name Time Method Treatment resistant rejection At biopsy or during study follow up after biopsy (expected average 12-months) Persistent rejection despite additional glucocorticoids and/or upscaling of maintenance immunosuppression
Interstitial fibrosis scores (IFTA) At biopsy or during study follow up after biopsy (expected average 12-months) features of interstitial fibrosis scores on the biopsy, with or without concurrent inflammation or tubulitis in the scarred areas on biopsy
BK virus associated nephropathy At biopsy or during study follow up after biopsy (expected average 12-months) biopsy evidence of positive SV40 stain in tubules
Proteinomic signature At biopsy or during study follow up after biopsy (expected average 12-months) mass spectrometry or spatial proteinomic changes between groups
All cause graft loss At biopsy or during study follow up after biopsy (expected average over 60-months) Graft loss - death censored and death with functioning graft
Biopsy proven acute rejection At biopsy or during study follow up after biopsy (expected average 12-months) Based on current Banff scoring system - features of acute rejection, , any subtype
Kidney function At biopsy or during study follow up after biopsy (expected average 12-months) Based on blood creatinine, eGFR
Death censored graft loss (DCGL) At biopsy or during study follow up after biopsy (expected average over 60-months) Graft loss - excluding cases of death with functioning graft
Delayed graft function (DGF) At biopsy or during study follow up after biopsy (within 7 days of transplantation) Need for dialysis within 7 days of transplantation
Surrogate end-points At biopsy or during study follow up after biopsy (expected average 12-months) eGFR slow and iBOX score
Biopsy evidence of borderline rejection At biopsy or during study follow up after biopsy (expected average 12-months) Based on current Banff scoring system - features of inflammation but not meeting acute rejection criteria
Chronic rejection At biopsy or during study follow up after biopsy (expected average 12-months) Based on current Banff scoring system with features of chronic rejection, any subtype
Albuminuria At biopsy or during study follow up after biopsy (expected average 12-months) Based on urine albumin to creatinine ratio
Donor to recipient mismatches At biopsy or during study follow up after biopsy (expected average 12-months) genomic/molecular level, HLA and non-HLA
Trial Locations
- Locations (1)
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia