Spatial Transcriptomics in Kidney Transplantation

Kidney Injury Clinical Trial

— SPACE-KiT  

Official title:

Spatial Transcriptomics in Kidney Transplantation

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06288425
• Other study ID #: SPACE-KIT
• Status: Enrolling by invitation
• Start date: April 3, 2024
• Est. completion date: January 1, 2035

Study information

• Verified date: April 2024
• Source: Western Sydney Local Health District
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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 information / eligibility

• Status: Enrolling by invitation
• Enrollment: 500
• Est. completion date: January 1, 2035
• Est. primary completion date: January 1, 2030
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Kidney Injury

Intervention

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

Locations

Country	Name	City	State
Australia	Westmead Hospital	Westmead	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Western Sydney Local Health District

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Kidney biopsy transcriptomic signature	Based on bulk and/or spatial transcriptomic experiments	At biopsy - based on collected tissue sample
Primary	Kidney cell type composition	Cell type phenotyping of immune and kidney cell types	At biopsy - based on collected tissue sample
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Kidney function	Based on blood creatinine, eGFR	At biopsy or during study follow up after biopsy (expected average 12-months)
Secondary	Albuminuria	Based on urine albumin to creatinine ratio	At biopsy or during study follow up after biopsy (expected average 12-months)
Secondary	Surrogate end-points	eGFR slow and iBOX score	At biopsy or during study follow up after biopsy (expected average 12-months)
Secondary	Donor to recipient mismatches	genomic/molecular level, HLA and non-HLA	At biopsy or during study follow up after biopsy (expected average 12-months)
Secondary	Proteinomic signature	mass spectrometry or spatial proteinomic changes between groups	At biopsy or during study follow up after biopsy (expected average 12-months)