Kidney Transplant Rejection, Transplant Complication
Conditions
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
Interventions
DIAGNOSTIC_TESTBiomarker discovery and validation - with focus on genomic biomarkers
Biomarker discovery and validation - with focus on genomic biomarkers
Sponsors
Western Sydney Local Health District
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Death | Any time during or after biopsy (expected over 60-months) | Death |
| 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 |
| Delayed Graft Function (DGF) | within the first 7 days post transplantation | Need for dialysis within the first 7 days post transplantation |
| Kidney function | Months 1, 3, 12, 24, 36, 48, 60, 120 post transplantation | serum creatinine and eGFR post transplantation |
| Albuminuria | Months 1, 3, 12 any time after 12-months trnasplantation | albumin in the urine (UACR) |
| 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 |
| 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 |
| 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 |
| BK virus complications | At biopsy or during study follow up after biopsy (expected average 12-months) | Viremia or virus associated nephropathy |
| 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 |
| 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 |
| Kidney biopsy transcriptomic signature | At biopsy - based on collected tissue sample | Based on bulk and/or spatial transcriptomic experiments |
| 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 |
| Recurrent disease | At biopsy or during study follow up after biopsy (expected average 60-months) | recurrence of original disease causing kidney failure |
| All cause graft loss | At biopsy or during study follow up after biopsy (expected average over 60-months) | DCGL or death with functioning graft |
Contacts
Primary ContactJennifer SY Li, MBBS, FRACP
Backup ContactPhilip J O'Connell, MBBS, FRACP
Outcome results
None listed