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Kidney Week

Abstract: FR-PO070

Nephrectomy Induced Renal Repair After AKI Prevents Progression to CKD by an Early Immunosuppressive Action

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Moonen, Lies, University of Antwerp, Wilrijk, Belgium
  • Cuypers, Bart, University Of Antwerp, Antwerp, Belgium
  • Meysman, Pieter, University of Antwerp, Wilrijk, Belgium
  • Laukens, Kris, Universiteit Antwerpen, Antwerpen, Belgium
  • D'Haese, Patrick C., University Antwerp, Edegem, Belgium
  • Vervaet, Benjamin Arthur, University Antwerp, Edegem, Belgium

Group or Team Name

  • Laboratory of Pathophysiology, University of Antwerp
Background

Enhanced renal repair is defined as the remarkable repair of an acutely injured kidney upon removal of the healthy contralateral kidney. If the latter kidney is left in place, repair is only marginal and the injured kidney turns fibrotic. It is yet unclear to which extent and by which molecular mechanism a nephrectomy is able to alter the fate of injured kidney cells.

Methods

Acute kidney injury was induced by left ischemia/reperfusion (I/R) after which either right nephrectomy (Nx) or mock-Nx was performed 3 days later. Wild type C57BL/6J mice underwent 21 min of ischemia at 36°C. Control mice underwent mock-I/R and mock-Nx surgery. Mice were euthanized at either 7 days or 6 weeks after I/R. Kidneys were weighed and qPCR analysis of the profibrotic genes Col1, Col4, TGFbeta and CCN2 was performed. Masson/H&E stain was used to microscopically evaluate histopathology and the extent of collagen deposition. RNA-sequencing was used to compare differential gene expression.

Results

In the I/R without Nx group the median left kidney-to-body weight ratio (mg/g) at week 6 was 2.8 (range 2.1-3.1), whereas that of its right healthy kidney was 6.7 (range 6.4-7.0), indicating severe atrophy in the injured left kidney. In the Nx group, left kidney-to-body ratio was 6.9 (range 6.0-7.3) and that of its right kidney at the time of Nx 6.5 (range 5.9-7.5). When no Nx was performed, Col1, Col4, TGFbeta and CCN2 were upregulated 18-, 5-, 7- and 3-fold compared to controls at week 6, respectively. In case of Nx, this decreased to 5-, 2-, 2-, and 0-fold upregulation. On a histological level, Nx strongly attenuated cortical atrophy and tubulo-interstitial fibrosis. Preliminary whole transcriptome RNA-seq analysis at day 7 showed differential expression of 534 genes (257 up, 277 down) of which immune response and MAPK pathways were most significantly downregulated upon Nx.

Conclusion

In conclusion, Nx performed 3 days after I/R has an early immunosuppressive action and attenuates renal atrophy and fibrosis in C57BL/6J mice. This murine model is a useful alternate tool to further study the mechanism of physiology-driven enhanced renal recovery.