Kidney Injury, Transplant Complication
Conditions
Brief 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
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
Interventions
OTHERNon interventional
Non interventional. Review of clinical, biopsy (histopathological and molecular) features associated with rejection and non-rejection pathology diagnosis
Sponsors
Western Sydney Local Health District
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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 |
|---|---|---|
| Kidney biopsy features | At biopsy or during study follow up following biopsy during study (expected 12-months) | Based on the pathology subtype at original diagnosis |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Delayed graft function (DGF) | At biopsy or during study follow up after biopsy (within 7 days of transplantation) | Need for dialysis within 7 days of transplantation |
| Biopsy evidence of borderline rejection | At biopsy or during study follow up after biopsy (expected average 12-months) | Based on current Banff scoring system - features of inflammation but not meeting acute rejection criteria |
| Biopsy proven acute rejection | At biopsy or during study follow up after biopsy (expected average 12-months) | Based on current Banff scoring system - features of acute rejection, , any subtype |
| Chronic rejection | At biopsy or during study follow up after biopsy (expected average 12-months) | Based on current Banff scoring system with features of chronic rejection, any subtype |
| Interstitial fibrosis scores (IFTA) | At biopsy or during study follow up after biopsy (expected average 12-months) | features of interstitial fibrosis scores on the biopsy, with or without concurrent inflammation or tubulitis in the scarred areas on biopsy |
| All cause graft loss | At biopsy or during study follow up after biopsy (expected average over 60-months) | Graft loss - death censored and death with functioning graft |
| Kidney function | At biopsy or during study follow up after biopsy (expected average 12-months) | Based on blood creatinine, eGFR |
| Albuminuria | At biopsy or during study follow up after biopsy (expected average 12-months) | Based on urine albumin to creatinine ratio |
| Surrogate end-points | At biopsy or during study follow up after biopsy (expected average 12-months) | eGFR slow and iBOX score |
| Donor to recipient mismatches | At biopsy or during study follow up after biopsy (expected average 12-months) | genomic/molecular level, HLA and non-HLA |
| Proteinomic signature | At biopsy or during study follow up after biopsy (expected average 12-months) | mass spectrometry or spatial proteinomic changes between groups |
| BK virus associated nephropathy | At biopsy or during study follow up after biopsy (expected average 12-months) | biopsy evidence of positive SV40 stain in tubules |
| Death censored graft loss (DCGL) | At biopsy or during study follow up after biopsy (expected average over 60-months) | Graft loss - excluding cases of 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 |
Countries
Australia
Outcome results
None listed