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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:
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| No rejection, normal biopsy (controls) | Normal biopsy - no acute tubular injury (ATI), rejection or any other pathology |
| |
| Acute kidney injury without evidence of rejection | Biopsy features of acute tubular injury but no evidence of rejection |
| |
| Subclinical Rejection | Biopsy features of injury and inflammation but not meeting current diagnostic criteria for acute or chronic rejection |
| |
| Acute rejection | Biopsy features of T-cell mediated, antibody-mediated, or mixed rejection |
| |
| Isolated vascular rejection | Biopsy features of inflammation in the blood vessels only |
| |
| Isolated glomerulitis | Biopsy features of inflammation in the glomeruli only |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Non interventional | Other | Non interventional. Review of clinical, biopsy (histopathological and molecular) features associated with rejection and non-rejection pathology diagnosis |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Death censored graft loss (DCGL) |
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Inclusion Criteria:
All participants included in the study must be age ≥ 18 years old at time of enrolment and
Exclusion Criteria:
Patients will be excluded from the study if they are
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Kidney transplant (or kidney-pancreas transplant) recipients consenting to this study.
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| Name | Affiliation | Role |
|---|---|---|
| Jen Li, FRACP | Westmead Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Westmead Hospital | Westmead | New South Wales | 2145 | Australia |
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Dedicated study samples will be collected at baseline and additional time-points based on the study group. Samples will be sent for processing and biobanking at the Westmead Institute for Medical Research
Blood sampling: all patients will submit blood samples for extraction of genomic material (eg DNA, RNA), peripheral blood mononuclear cells (PBMC) and plasma/serum.
Kidney biopsy sample: a dedicated sample of kidney biopsy may be collected for the study with the patient's permission. The core will be split so that half the sample is collected in specialised media for spatial transcriptomics and other molecular/proteinomic studies.
Additional sampling: Mid-stream urine sample for pellet and supernatant and then stored at -80'c, Faecal sample in dedicated gut microbiome kits and then stored at -80'c. These samples will be biobanked and may be used later for proteinomic or microbiome studies.
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| Chronic (active) rejection | Biopsy features of chronic rejection - T-cell, antibody or mixed types |
|
| BK virus associated nephropathy (BKVAN) | Biopsy features of SV40 positive staining in tubules to diagnose BKVAN |
|
Graft loss - excluding cases of death with functioning graft
| At biopsy or during study follow up after biopsy (expected average over 60-months) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| Kidney function | Based on blood creatinine, eGFR | At biopsy or during study follow up after biopsy (expected average 12-months) |
| Albuminuria | Based on urine albumin to creatinine ratio | At biopsy or during study follow up after biopsy (expected average 12-months) |
| Surrogate end-points | eGFR slow and iBOX score | At biopsy or during study follow up after biopsy (expected average 12-months) |
| Donor to recipient mismatches | genomic/molecular level, HLA and non-HLA | At biopsy or during study follow up after biopsy (expected average 12-months) |
| Proteinomic signature | mass spectrometry or spatial proteinomic changes between groups | At biopsy or during study follow up after biopsy (expected average 12-months) |