Spatial Transcriptomics in Kidney Transplantation (SPACE-KiT)

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

Study Overview

• Status: Enrolling by invitation
• Conditions: Kidney Injury; Transplant Complication
• Intervention / Treatment: Other: Non interventional

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

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Kidney transplant (or kidney-pancreas transplant) recipients consenting to this study.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

8

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
No rejection, normal biopsy (controls); Normal biopsy - no acute tubular injury (ATI), rejection or any other pathology	Other: Non interventional; 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	Other: Non interventional; 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	Other: Non interventional; 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	Other: Non interventional; 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	Other: Non interventional; 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	Other: Non interventional; 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	Other: Non interventional; 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	Other: Non interventional; Non interventional. Review of clinical, biopsy (histopathological and molecular) features associated with rejection and non-rejection pathology diagnosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kidney biopsy features	Based on the pathology subtype at original diagnosis	At biopsy or during study follow up following biopsy during study (expected 12-months)
Kidney biopsy transcriptomic signature	Based on bulk and/or spatial transcriptomic experiments	At biopsy - based on collected tissue sample
Kidney cell type composition	Cell type phenotyping of immune and kidney cell types	At biopsy - based on collected tissue sample

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment resistant rejection	Persistent rejection despite additional glucocorticoids and/or upscaling of maintenance immunosuppression	At biopsy or during study follow up after biopsy (expected average 12-months)
Delayed graft function (DGF)	Need for dialysis within 7 days of transplantation	At biopsy or during study follow up after biopsy (within 7 days of transplantation)
Biopsy evidence of borderline rejection	Based on current Banff scoring system - features of inflammation but not meeting acute rejection criteria	At biopsy or during study follow up after biopsy (expected average 12-months)
Biopsy proven acute rejection	Based on current Banff scoring system - features of acute rejection, , any subtype	At biopsy or during study follow up after biopsy (expected average 12-months)
Chronic rejection	Based on current Banff scoring system with features of chronic rejection, any subtype	At biopsy or during study follow up after biopsy (expected average 12-months)
Interstitial fibrosis scores (IFTA)	features of interstitial fibrosis scores on the biopsy, with or without concurrent inflammation or tubulitis in the scarred areas on biopsy	At biopsy or during study follow up after biopsy (expected average 12-months)
BK virus associated nephropathy	biopsy evidence of positive SV40 stain in tubules	At biopsy or during study follow up after biopsy (expected average 12-months)
Kidney function	Based on blood creatinine, eGFR	At biopsy or during study follow up after biopsy (expected average 12-months)
Albuminuria	Based on urine albumin to creatinine ratio	At biopsy or during study follow up after biopsy (expected average 12-months)
Surrogate end-points	eGFR slow and iBOX score	At biopsy or during study follow up after biopsy (expected average 12-months)
Donor to recipient mismatches	genomic/molecular level, HLA and non-HLA	At biopsy or during study follow up after biopsy (expected average 12-months)
Proteinomic signature	mass spectrometry or spatial proteinomic changes between groups	At biopsy or during study follow up after biopsy (expected average 12-months)
All cause graft loss	Graft loss - death censored and death with functioning graft	At biopsy or during study follow up after biopsy (expected average over 60-months)
Death censored graft loss (DCGL)	Graft loss - excluding cases of death with functioning graft	At biopsy or during study follow up after biopsy (expected average over 60-months)

Collaborators and Investigators

• Sponsor: Western Sydney Local Health District
• Investigators: Principal Investigator: Jen Li, FRACP, Westmead Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2024
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2035

Study Registration Dates

• First Submitted: February 3, 2024
• First Submitted That Met QC Criteria: February 24, 2024
• First Posted (Actual): March 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: SPACE-KIT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No