Kidney Injury
Conditions
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
Interventions
OTHERRetrospective review of histological features
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
Sponsors
Western Sydney Local Health District
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Inclusion criteria
1. Had a kidney biopsy (native kidney or transplant kidney included) after year 2000 2. Kidney biopsy sample sent to Westmead Hospital for clinical interpretation
Exclusion criteria
1. Patients who have never had a kidney biopsy performed 2. Biopsy sample not available at Westmead Hospital 3. No information on kidney function (serum creatinine or eGFR)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Surrogate end point of kidney function | During study follow up after biopsy (expected average 12-months) | eGFR slope |
| 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 |
| 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 |
| 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) |
| Albuminuria | At biopsy (time 0) or during study follow up after biopsy (expected average 12-months) | urine albumin to creatinine ratio |
| 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 |
Outcome results
None listed