Kidney Week

Abstract: PO0414

Contralateral Nephrectomy Stimulates Proliferation of Renal Epithelial Progenitor Cells After Unilateral Ischemia

Session Information

• AKI: Repair and Progression
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Moonen, Lies, Universiteit Antwerpen Laboratorium voor Pathofysiologie, Wilrijk, Antwerp, Belgium

Lies Moonen

• Lazzeri, Elena, Universita degli Studi di Firenze Dipartimento di Scienze Biomediche Sperimentali e Cliniche Mario Serio, Firenze, Toscana, Italy

Elena Lazzeri,

• Peired, Anna Julie, Universita degli Studi di Firenze Dipartimento di Scienze Biomediche Sperimentali e Cliniche Mario Serio, Firenze, Toscana, Italy

Anna Julie Peired,

• Conte, Carolina, Universita degli Studi di Firenze Dipartimento di Scienze Biomediche Sperimentali e Cliniche Mario Serio, Firenze, Toscana, Italy

Carolina Conte,

• Romagnani, Paola, Universita degli Studi di Firenze Dipartimento di Scienze Biomediche Sperimentali e Cliniche Mario Serio, Firenze, Toscana, Italy

Paola Romagnani,

• D'Haese, Patrick, Universiteit Antwerpen Laboratorium voor Pathofysiologie, Wilrijk, Antwerp, Belgium

Patrick D'Haese,

• Vervaet, Benjamin Arthur, Universiteit Antwerpen Laboratorium voor Pathofysiologie, Wilrijk, Antwerp, Belgium

Benjamin Arthur Vervaet,

Group or Team Name

• Laboratory of Pathophysiology

Background

Acute kidney injury is a global health concern and important risk factor for the development of chronic kidney disease. Crucial for successful renal recovery after AKI is the proliferation of surviving tubular epithelial cells. We established a murine model in which functional and histological recovery of a kidney, injured by ischemia, is enhanced by removal of the contralateral kidney, i.e. nephrectomy-induced recovery. The epithelial reparative response in this unique model has not been investigated, yet can provide new insights in the inherent regenerative potential of the renal epithelium.

Methods

AKI was induced in two different mice strains by left unilateral ischemia/reperfusion (UIRI) after which either right nephrectomy (Nx) or no Nx was performed on day 3. In R26R^tdTomato mice kidney-to-body-weight ratio, renal function (serum creatinine) and fibrosis (Sirius Red histology) were measured at week 6. Additionally, renal tissue of PAX2/Confetti mice was processed to study clonal expansion by lineage pattern analysis of PAX2⁺ renal epithelial progenitor cells at day 28.

Results

When no Nx was performed after UIRI, a significant decrease in left kidney-to-body weight ratio along with increased fibrosis and functional loss were observed in the injured kidney at week 6 compared to controls. However, when Nx was performed, renal function and mass were preserved. During spontaneous repair after UIRI (i.e. without Nx) clonal analysis in PAX2/Confetti mice revealed a significant increase in clone size frequency from mainly monoclonal PAX2⁺ progenitor cells in controls to an increased number of multicellular clones. When Nx was performed after UIRI, this clonal expansion was further significantly stimulated. Likewise, the percentage of PAX2+ cells stimulated to divide (i.e. clonogenicity) was significantly higher when Nx was performed after UIRI (42%) as compared to when no Nx was performed (28%).

Conclusion

Nx overcomes loss of renal mass and function after UIRI. This enhanced recovery is at least established by increased clonogenicity and enhanced clonal expansion of renal progenitor cells that surpasses that of spontaneous repair after UIRI. Getting insight in the signaling mechanisms by which nephrectomy achieves this response may open new therapeutic research avenues.