Spatial Transcriptomics in Kidney Transplantation

NCT ID: NCT06288425

Last Updated: 2024-04-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ENROLLING_BY_INVITATION

Total Enrollment

500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-04-03

Study Completion Date

2035-01-01

Brief Summary

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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

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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

Conditions

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Transplant Complication Kidney Injury

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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No rejection, normal biopsy (controls)

Normal biopsy - no acute tubular injury (ATI), rejection or any other pathology

Non interventional

Intervention Type OTHER

Non interventional. Review of clinical, biopsy (histopathological and molecular) features associated with rejection and non-rejection pathology diagnosis

Acute kidney injury without evidence of rejection

Biopsy features of acute tubular injury but no evidence of rejection

Non interventional

Intervention Type OTHER

Non interventional. Review of clinical, biopsy (histopathological and molecular) features associated with rejection and non-rejection pathology diagnosis

Subclinical Rejection

Biopsy features of injury and inflammation but not meeting current diagnostic criteria for acute or chronic rejection

Non interventional

Intervention Type OTHER

Non interventional. Review of clinical, biopsy (histopathological and molecular) features associated with rejection and non-rejection pathology diagnosis

Acute rejection

Biopsy features of T-cell mediated, antibody-mediated, or mixed rejection

Non interventional

Intervention Type OTHER

Non interventional. Review of clinical, biopsy (histopathological and molecular) features associated with rejection and non-rejection pathology diagnosis

Isolated vascular rejection

Biopsy features of inflammation in the blood vessels only

Non interventional

Intervention Type OTHER

Non interventional. Review of clinical, biopsy (histopathological and molecular) features associated with rejection and non-rejection pathology diagnosis

Isolated glomerulitis

Biopsy features of inflammation in the glomeruli only

Non interventional

Intervention Type OTHER

Non interventional. Review of clinical, biopsy (histopathological and molecular) features associated with rejection and non-rejection pathology diagnosis

Chronic (active) rejection

Biopsy features of chronic rejection - T-cell, antibody or mixed types

Non interventional

Intervention Type OTHER

Non interventional. Review of clinical, biopsy (histopathological and molecular) features associated with rejection and non-rejection pathology diagnosis

BK virus associated nephropathy (BKVAN)

Biopsy features of SV40 positive staining in tubules to diagnose BKVAN

Non interventional

Intervention Type OTHER

Non interventional. Review of clinical, biopsy (histopathological and molecular) features associated with rejection and non-rejection pathology diagnosis

Interventions

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Non interventional

Non interventional. Review of clinical, biopsy (histopathological and molecular) features associated with rejection and non-rejection pathology diagnosis

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Western Sydney Local Health District

OTHER

Sponsor Role lead

Responsible Party

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Jennifer Li

CPI, Nephrologist and Transplant Physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jen Li, FRACP

Role: PRINCIPAL_INVESTIGATOR

Westmead Hospital

Locations

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Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Countries

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Australia

Other Identifiers

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SPACE-KIT

Identifier Type: -

Identifier Source: org_study_id

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