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The investigators aim to develop a clinically validated, histological acute tubular injury (ATI) scoring system to help improve diagnostic precision and predict clinical outcomes following ATI.
To use an unbiased, data-driven approach, correlating pathological features (including digital pathology), key signatures using spatial technologies (transcriptomics or proteinomics) with relevant clinical outcomes. Spatial technologies (including spatial transcriptomics and spatial proteinomics) allow the use of 'precision pathology' to study the critical link between molecular characteristics to histological structure.
The study is an investigator-led, retrospective, observational cohort study. This study is intended to be in perpetuity and there will be regular reporting to the local HREC (Western Sydney Local Health District, WSLHD)
Primary aim: the investigators aim to derive a clinically validated scoring system for acute kidney injury and iteratively improve its performance through machine learning algorithms over time.
Secondary aims:
All participants included in the study must be age ≥ 18 years old at time of enrolment and
This will include groups with
Collection of health related data will be through review of primary medical records to improve the diagnostic utility of kidney biopsies performed to evaluate the cause of AKI.
The investigators will also be requesting waiver of consent for access to histopathology slides and residual kidney tissue
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acute tubular injury (ATI) only | Kidney biopsy with features of acute tubular injury only, no other pathology detected |
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| Concurrent diagnosis of acute tubular injury with any other pathology | Kidney biopsy with features of acute tubular injury AND other pathology. Non-ATI pathology includes but not limited to diagnosis of any type of glomerulonephritis, vasculitis, hereditary nephritis, thrombotic microangiopathy, kidney transplant rejection, podocytopathy, diabetic or hypertensive nephropathy, interstitial nephritis, pyelonephritis, amyloidosis, malignancy or paraneoplastic related kidney disease. |
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| Biopsies with no acute tubular injury (neg control) | Kidney biopsy with any diagnosis other than (no features of) acute tubular injury |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Retrospective review of histological features | Other | Correlate histopathology characteristics of acute kidney injury with molecular signatures, kidney function and aetiology of acute kidney injury to derive clinically validated scoring system for acute kidney injury and acute tubular injury |
| Measure | Description | Time Frame |
|---|---|---|
| Histopathology characteristics of acute tubular injury (ATI) | Biopsy features including tubular dilatation, interstitial oedema, epithelial vacuolization and disrupted brush border integrity | Specific for the biopsy/tissue, no time frame after |
| Kidney function | Kidney function based on blood tests collected from routine clinical care | At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) |
| Correlation of biopsy findings with kidney function at time of biopsy and longitudinally | Molecular signatures of injury | At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) |
| Measure | Description | Time Frame |
|---|---|---|
| Surrogate end point of kidney function | eGFR slope | During study follow up after biopsy (expected average 12-months) |
| Albuminuria | urine albumin to creatinine ratio |
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Inclusion Criteria:
Exclusion Criteria:
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Patients who had a kidney biopsy performed for any clinical indication, with biopsy sample sent to Westmead Hospital for review
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Access to histology slides: These slides are stored in the anatomical pathology department at Westmead Hospital/NSW Health Pathology. We will digitally scan these slides. Digital slides will be labelled with the study ID. Slides will be returned after scanning.
Request access to kidney tissue blocks: This includes formalin-fixed, paraffin embedded (FFPE) kidney blocks, and fresh frozen kidney embedded in OCT. These are requested after clinical use and interpretation of the biopsy has been completed. The exact methodology will be determined by the available technology at the time (there is rapid advancement in imaging and molecular technologies) and the utility to achieve the objectives in the study. These include, but not limited to preparing slides for spatial transcriptomics (RNA-sequencing), single-cell extraction and RNA sequencing, spatial proteinomics, mass spectrometry/proteinomics, high plex immunohistochemistry, imaging mass cytometry
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| At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) |
| Time to renal recovery | Kidney function return to baseline - based on any historical results before the biopsy date | At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) |
| Time to kidney failure | Deterioration (or no recovery) in kidney function where dialysis or transplantation is needed to sustain life | At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) |
| Chronic kidney disease | Deterioration (or without full recovery) in kidney function where chronic kidney disease is diagnosed based on clinical criteria | At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) |
| Response to treatment | Response to non-supportive therapy (eg steroids) | At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) |
| Genomic signatures | Transcriptomics (RNA) and microRNA (miRNA) extracted from the kidney biopsy | At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) |
| Cell types | Detection of immune or kidney cell types on kidney biopsy | At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) |