Western Sydney Kidney Injury Biopsy Study (WESTKiD)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Kidney Injury
• Intervention / Treatment: Other: Retrospective review of histological features

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

• Study Type: Observational
• Enrollment (Estimated): 1000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Patients who had a kidney biopsy performed for any clinical indication, with biopsy sample sent to Westmead Hospital for review

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acute tubular injury (ATI) only; Kidney biopsy with features of acute tubular injury only, no other pathology detected	Other: Retrospective 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
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.	Other: Retrospective 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
Biopsies with no acute tubular injury (neg control); Kidney biopsy with any diagnosis other than (no features of) acute tubular injury	Other: Retrospective 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Secondary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Western Sydney Local Health District

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): January 1, 2035
• Study Completion (Estimated): January 1, 2040

Study Registration Dates

• First Submitted: February 3, 2024
• First Submitted That Met QC Criteria: February 3, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries
• Other Study ID Numbers: WESTKiD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No