Clinical trial NCT06288425: Spatial Transcriptomics in Kidney Transplantation
Official title: Spatial Transcriptomics in Kidney Transplantation
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Transplant Complication
Kidney Injury
Lead sponsor: Western Sydney Local Health District
Sponsor class: OTHER
First posted: 2024-03-01
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Kidney transplant (or kidney-pancreas transplant) recipients consenting to this study.

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

Eligibility criteria: Inclusion Criteria:

All participants included in the study must be age ≥ 18 years old at time of enrolment and

1. able to provide informed consent (interpreter permitted) for enrolment
2. consenting to longitudinal follow up (can withdraw post enrolment)
3. consenting to provide samples for biobanking, including blood, urine, faecal and/or kidney biopsy tissue (collected prospectively, separate to routine care)

Exclusion Criteria:

Patients will be excluded from the study if they are

1. unable (or unwilling) to provide consent, or
2. have life-expectancy less than 6-months, or
3. have received a haematopoietic stem cell transplant in the past 5 years.

Primary outcomes:
measure: Kidney biopsy features
timeFrame: At biopsy or during study follow up following biopsy during study (expected 12-months)
measure: Kidney biopsy transcriptomic signature
timeFrame: At biopsy - based on collected tissue sample
measure: Kidney cell type composition
timeFrame: At biopsy - based on collected tissue sample
Secondary outcomes:
measure: All cause graft loss
timeFrame: At biopsy or during study follow up after biopsy (expected average over 60-months)
measure: Death censored graft loss (DCGL)
timeFrame: At biopsy or during study follow up after biopsy (expected average over 60-months)
measure: Treatment resistant rejection
timeFrame: At biopsy or during study follow up after biopsy (expected average 12-months)
measure: Delayed graft function (DGF)
timeFrame: At biopsy or during study follow up after biopsy (within 7 days of transplantation)
measure: Biopsy evidence of borderline rejection
timeFrame: At biopsy or during study follow up after biopsy (expected average 12-months)
measure: Biopsy proven acute rejection
timeFrame: At biopsy or during study follow up after biopsy (expected average 12-months)
measure: Chronic rejection
timeFrame: At biopsy or during study follow up after biopsy (expected average 12-months)
measure: Interstitial fibrosis scores (IFTA)
timeFrame: At biopsy or during study follow up after biopsy (expected average 12-months)
measure: BK virus associated nephropathy
timeFrame: At biopsy or during study follow up after biopsy (expected average 12-months)
measure: Kidney function
timeFrame: At biopsy or during study follow up after biopsy (expected average 12-months)
measure: Albuminuria
timeFrame: At biopsy or during study follow up after biopsy (expected average 12-months)
measure: Surrogate end-points
timeFrame: At biopsy or during study follow up after biopsy (expected average 12-months)
measure: Donor to recipient mismatches
timeFrame: At biopsy or during study follow up after biopsy (expected average 12-months)
measure: Proteinomic signature
timeFrame: At biopsy or during study follow up after biopsy (expected average 12-months)
Other outcomes:
Locations:
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
Study officials:
affiliation: Westmead Hospital
name: Jen Li, FRACP
role: PRINCIPAL_INVESTIGATOR
References: