GEnomic Medicine in Kidney Transplantation Study

Not yet recruiting

• Conditions: Transplant Complication; Kidney Transplant Rejection
• Interventions: Diagnostic Test: Biomarker discovery and validation - with focus on genomic biomarkers

• Registration Number: NCT06365411
• Lead Sponsor: Western Sydney Local Health District

Brief Summary

Investigator led, prospective, observational cohort study to detect genomic features which can predict outcomes following kidney transplantation.

1. Determine non-HLA genomic mismatches between donor-recipient pairs which impact kidney allograft survival following transplantation

2. Derive polygenic risk scores on pre-transplant blood and/or kidney biopsy samples which predict kidney allograft dysfunction

3. Derive polygenic risk scores on post-transplant blood and/or kidney biopsy samples which predict kidney allograft dysfunction

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-03-10
• Status Verified: 2024-04
• Study First Submitted QC: 2024-04-09
• Study First Posted: 2024-04-15
• Last Update Submitted: 2025-03-24
• Last Update Posted: 2025-03-28
• Study Start: 2025-06-03
• Primary Completion: 2030-01-01
• Study Completion: 2035-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 1000

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Kidney Transplant Recipients	Biomarker discovery and validation - with focus on genomic biomarkers	Enrolled at time of transplant or post transplant

Primary Outcome Measures

Name	Time	Method
Death censored graft loss (DCGL)	At biopsy or during study follow up after biopsy (expected average over 60-months)	Loss of functioning kidney transplant (not counted if patient died with functioning graft)
Biopsy proven rejection (BPAR)	At biopsy or during study follow up after biopsy (expected average 12-months)	Rejection diagnosed on kidney transplant biopsy

Secondary Outcome Measures

Name	Time	Method
Albuminuria	Months 1, 3, 12 any time after 12-months trnasplantation	albumin in the urine (UACR)
Death	Any time during or after biopsy (expected over 60-months)	Death
Delayed Graft Function (DGF)	within the first 7 days post transplantation	Need for dialysis within the first 7 days post transplantation
chronic rejection; chronic transplant glomerulopathy; and interstitial fibrosis and tubular atrophy (IFTA) scores	At biopsy or during study follow up after biopsy (expected average over 12-months)	Based on banff scoring for kidney biopsies
Major cardiovascular complications	At biopsy or during study follow up after biopsy (expected average 60-months)	3-point MACE: non fatal stroke, non fatal myocardial infarction, cardiovascular death
Kidney cell type composition	At biopsy - based on collected tissue sample	Cell type phenotyping of immune and kidney cell types
Proteinomic signature	At biopsy or during study follow up after biopsy (expected average 12-months)	mass spectrometry or spatial proteinomic results
Hospital admission or emergency attendance	At biopsy or during study follow up after biopsy (expected average 12-months)	Hospital admission or emergency department visit for any reason
Kidney function	Months 1, 3, 12, 24, 36, 48, 60, 120 post transplantation	serum creatinine and eGFR post transplantation
BK virus complications	At biopsy or during study follow up after biopsy (expected average 12-months)	Viremia or virus associated nephropathy
Kidney biopsy transcriptomic signature	At biopsy - based on collected tissue sample	Based on bulk and/or spatial transcriptomic experiments
All cause graft loss	At biopsy or during study follow up after biopsy (expected average over 60-months)	DCGL or death with functioning graft
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
Surrogate end-point markers	Months 3, 12, 24, 36, 48 and 60, 120 post transplantation	eGFR slope and iBOX scores
Borderline rejeciton	At biopsy or during study follow up after biopsy (expected average 12-months)	Based on banff scoring criteria for kidney biospies
Major infectious complications	At biopsy or during study follow up after biopsy (expected average 60-months)	any major fungal, bacterial or viral infection
Malignancy post transplantation	At biopsy or during study follow up after biopsy (expected average 60-months)	any cancer type
Recurrent disease	At biopsy or during study follow up after biopsy (expected average 60-months)	recurrence of original disease causing kidney failure