GEnomic Medicine in Kidney Transplantation Study (GEM-KiT)

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

Study Overview

• Status: Not yet recruiting
• Conditions: Kidney Transplant Rejection; Transplant Complication
• Intervention / Treatment: Diagnostic test: Biomarker discovery and validation - with focus on genomic biomarkers

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Jennifer SY Li, MBBS, FRACP; Phone Number: 612 88905555; Email: jennifer.li@health.nsw.gov.au
• Study Contact Backup: Name: Philip J O'Connell, MBBS, FRACP; Phone Number: 612 88905555; Email: philip.oconnell@sydney.edu.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Adult, kidney transplant (or kidney-pancreas transplant) recipients

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

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Kidney Transplant Recipients; Enrolled at time of transplant or post transplant	Diagnostic test: Biomarker discovery and validation - with focus on genomic biomarkers; Biomarker discovery and validation - with focus on genomic biomarkers

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Western Sydney Local Health District

Study record dates

Study Major Dates

• Study Start (Estimated): June 3, 2025
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2035

Study Registration Dates

• First Submitted: March 10, 2024
• First Submitted That Met QC Criteria: April 9, 2024
• First Posted (Actual): April 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: GEM-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
• product manufactured in and exported from the U.S.: No