Abstract: FR-PO192
Pathomics Reveals Histomorphological Recovery During Nephrectomy-Induced Kidney Repair
Session Information
- AKI: Mechanisms - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Van Campen, Elien, Universiteit Antwerpen Faculteit Farmaceutische Biomedische en Diergeneeskundige Wetenschappen, Wilrijk, Belgium
- Moonen, Lies, Universiteit Antwerpen Faculteit Farmaceutische Biomedische en Diergeneeskundige Wetenschappen, Wilrijk, Belgium
- Boor, Peter, Universitatsklinikum Aachen, Aachen, Nordrhein-Westfalen, Germany
- Vervaet, Benjamin Arthur, Universitatsklinikum Aachen, Aachen, Germany
Group or Team Name
- Laboratory of Pathophysiology and Laboratory of Nephropathology.
Background
Acute kidney injury (AKI) is a common disease, that can progress to chronic kidney disease (CKD). Nephrectomy (Nx)-induced repair describes the phenomenon of a remarkable functional and structural recovery of unilateral AKI upon removal of the contralateral healthy kidney. The underlying mechanisms remain largely unknown and a thorough analysis of structural recovery remains challenging. Therefore, we applied next generation morphometry and pathomics to comprehensively quantitate structural alterations in a validated model of Nx-induced repair after left unilateral ischemia reperfusion injury (UIRI).
Methods
C57BL/6J mice were divided into 3 groups: UIRI+Sham (n=54), UIRI+Nx (n=36), or healthy controls (n=6). Kidneys of all mice were acquired at days 1 to 7 and days 21, and 42 after UIRI (n=6/timepoint). Sham-surgery or Nx of the right kidney were performed 3 days after UIRI. Digitized PAS-stained tissue sections (whole slide images) were analysed using our pathomics pipeline.
Results
Quantitative pathomics on over 706090 tubules revealed a progressive decay of overall tubular area after UIRI with a loss of 22% by day 42 compared to controls. In accordance with tubular atrophy, tubular cross-sectional diameters (µm) and sizes (µm2) became smaller after UIRI by 15% (diameter) and 32% (size) of control values from day 3 onwards. Nx prevented these changes, minimizing loss of tubular area to 5%. The mean tubular diameters and areas were comparable to control values, although their overall distribution changed from a bimodal (healthy control) to a unimodal distribution appearance, originating from the dimensional differences of cortical and medullary tubules. After UIRI, interstitial area steadily increased to 20% above controls by day 21. Nx abrogated this progression, with an interstitial area remaining stable at an average of 6.5% above controls.
Conclusion
Large-scale, automated quantification of structural alterations revealed the distinct histopathological fates of an acute injured kidney in comparison to its rescue by nephrectomy. These data show the utility of pathomics to investigate spatiotemporal histological shifts during kidney injury and repair.