Molecular Analysis of Diabetic Kidney Disease Biopsies
- Conditions
- Kidney Disease, ChronicDiabetic Nephropathies
- Interventions
- Other: RNA sequencing
- Registration Number
- NCT04029402
- Lead Sponsor
- Unity Health Toronto
- Brief Summary
Despite decades of research, the pathogenesis of human diabetic kidney disease remains largely unclear. Our goal is to use archived human kidney biopsy tissue from patients with and with diabetic nephropathy to identify new molecules that drive and/or protect against disease progression. We will use RNA sequencing to identify transcriptomic changes that associate with histologic and functional outcomes.
- Detailed Description
RESEARCH OBJECTIVES A. To identify differences in transcription profiles obtained from residual kidney tissue which was obtained for clinical purposes.
B. To identify differences in transcription profile between patients whose loss of kidney function progresses rapidly (eGFR decline ≥4ml/min/year) and in whom it progresses more slowly (eGFR decline \<4ml/min/year).
C. To identify differences in transcription profile between predominantly glomerular and predominantly tubulointerstitial histopathological types .
D. To identify new pathogenetic pathways that may become targets for therapeutic intervention
METHODS The planned study centres on the use of archival biopsy material that is superfluous to what is or would be needed for clinical care (01/01/1995 to 31/05/2018 , n= approximately 400-500). Archived samples will be collected from St. Michael's Hospital and a number of collaborating centres, including but not limited to University of British Columbia, the University of Manitoba, and the University of Ottawa.
RNA will be extracted from the biopsy material using either the core that has been used for immunofluorescence microscopy and is stored at -80˚C, and/or the core that is formalin-fixed, embedded in paraffin wax and stored at room temperature. The RNA thereby extracted will be subjected to detailed interrogation by RNASeq to quantify the expression level of mRNAs (transcriptome) and compare differences, as indicated in the research objectives detailed above. The transcriptome will then be related to the clinical course (eGFR decline) and histopathological changes, in addition to examining potentially pathogenetically important and that are amenable to therapeutic intervention.
Histopathology will also be performed and classified according to established systems.
Clinical information that would be retrieved from patients' medical records are listed below.
Clinical data
1. Age
2. Gender
3. Ethnicity
4. Diabetes history
5. Diabetes type: 1, 2
6. Retinopathy history
7. Smoking history
8. Medications
9. Comorbidities
10. Past medical history
11. Primary nephrologist Laboratory data (prior to biopsy, at biopsy and post-biopsy)
12. Renal function measures and calculations. For example:
i. Serum creatinine, eGFR ii. Change in creatinine and eGFR iii. Urinary albumin:creatinine values and ratio (ACR) iv. Urine protein:creatinine values and ratio (PCR) v. Urinary protein excretion rate (UPEx) vi. Changes in ACR, PCR, UPEx
13. Diabetes measures and calculations. Biopsy data
14. Biopsy related data
Each site will locally maintain a confidential Master Linking Log.
De-identified data will be entered into a secure REDCap database that is hosted by St. Michael's Hospital.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 500
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Diabetic kidney disease RNA sequencing Patients with archived biopsies with a pathologic diagnosis of diabetic kidney disease, interstitial fibrosis/tubular atrophy, or nephrosclerosis. Healthy controls RNA sequencing Potential living donors with archived biopsies performed as part of their donor workup and with no diagnostic abnormalities
- Primary Outcome Measures
Name Time Method Renal function change Baseline biopsy Slope of eGFR decline
Interstitial fibrosis Baseline biopsy Extent of interstitial fibrosis in kidney biopsy assessed using a semi-quantitative scale on light microscopy of biopsy sections
Glomerulosclerosis Baseline biopsy Extent of glomerulosclerosis in kidney biopsy assessed using a semi-quantitative scale on light microscopy of biopsy sections
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (4)
University of Manitoba
🇨🇦Winnipeg, Manitoba, Canada
University of British Columbia
🇨🇦Vancouver, British Columbia, Canada
University of Ottawa
🇨🇦Ottawa, Ontario, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada