Western Sydney Kidney Injury Biopsy Study
- Conditions
- Kidney Injury
- Interventions
- Other: Retrospective review of histological features
- Registration Number
- NCT06254677
- Lead Sponsor
- Western Sydney Local Health District
- Brief Summary
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.
- Detailed Description
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:
* Derive a spatially resolved transcriptomic signature of acute kidney injury (AKI)
* Derive accurate transcriptomic signatures aligned with key cell types in AKI
* Derive unique gene signatures to differentiate different causes of AKI
All participants included in the study must be age ≥ 18 years old at time of enrolment and
1. Had a kidney transplant at any time after the year 2000
2. Kidney biopsy sample sent to Westmead Hospital for clinical interpretation
3. Have information regarding kidney function available.
This will include groups with
1. Acute tubular injury (ATI) only
2. ATI concurrently diagnosed with any other pathology on biopsy
3. Biopsies with no ATI (negative control)
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
* Histopathology slides, which were created and analysed as part of routine clinical care.
* Residual kidney tissue, either as paraffin blocks or fresh frozen tissue
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 1000
- Had a kidney biopsy (native kidney or transplant kidney included) after year 2000
- Kidney biopsy sample sent to Westmead Hospital for clinical interpretation
- Patients who have never had a kidney biopsy performed
- Biopsy sample not available at Westmead Hospital
- No information on kidney function (serum creatinine or eGFR)
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Biopsies with no acute tubular injury (neg control) Retrospective review of histological features Kidney biopsy with any diagnosis other than (no features of) acute tubular injury Acute tubular injury (ATI) only Retrospective review of histological features Kidney biopsy with features of acute tubular injury only, no other pathology detected Concurrent diagnosis of acute tubular injury with any other pathology Retrospective review of histological features 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.
- Primary Outcome Measures
Name Time Method Histopathology characteristics of acute tubular injury (ATI) Specific for the biopsy/tissue, no time frame after Biopsy features including tubular dilatation, interstitial oedema, epithelial vacuolization and disrupted brush border integrity
Correlation of biopsy findings with kidney function at time of biopsy and longitudinally At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) Molecular signatures of injury
Kidney function At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) Kidney function based on blood tests collected from routine clinical care
- Secondary Outcome Measures
Name Time Method Albuminuria At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) urine albumin to creatinine ratio
Chronic kidney disease At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) Deterioration (or without full recovery) in kidney function where chronic kidney disease is diagnosed based on clinical criteria
Genomic signatures At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) Transcriptomics (RNA) and microRNA (miRNA) extracted from the kidney biopsy
Time to renal recovery At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) Kidney function return to baseline - based on any historical results before the biopsy date
Surrogate end point of kidney function During study follow up after biopsy (expected average 12-months) eGFR slope
Response to treatment At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) Response to non-supportive therapy (eg steroids)
Cell types At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) Detection of immune or kidney cell types on kidney biopsy
Time to kidney failure At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) Deterioration (or no recovery) in kidney function where dialysis or transplantation is needed to sustain life