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Abstract: FR-PO060

Experimental Aristolochic Acid Nephropathy: A Model to Study AKI-to-CKD Transition

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Jadot, Inès, University of Namur, Namur, Belgium
  • Juszczak, Florian, Laboratory of Molecular Biology, University of Mons, Belgium, NIMY (MONS), Belgium
  • Botton, Olivia, University of Namur, Namur, Belgium
  • Nortier, Joelle L., Hospital Erasme, Brussels, Belgium
  • Decleves, Anne-Emilie, Laboratory of Molecular Biology, University of Mons, Belgium, NIMY (MONS), Belgium
  • Caron, Nathalie, University of Namur, Namur, Belgium
Background

Even though impaired kidney function is classified into two distinct categories, the acute (AKI) and the chronic (CKD) kidney disease, recent epidemiologic and mechanistic studies demonstrated that AKI and CKD are interconnected. Indeed, AKI is a risk factor for the development of CKD. In this regard, molecular and cellular mechanisms underlying the AKI-to-CKD transition are unclear, mainly due to a lack of appropriate experimental models. In the present study, we aim to highlight the benefit of using the experimental aristolochic acid (AA) nephropathy (AAN) model to further delineate the progression of CKD from an AKI episode.

Methods

C57BL/6J male mice were randomly subjected to daily ip injection of vehicle or AAI solution (3,5mg/kg) for 4 days. Mice were then euthanized at different time-points to determine key biological markers of the AKI-to-CKD transition using urine and plasma assays, histological and molecular analyses.

Results

AA-treated mice developed a biphasic evolution of renal dysfunction and morphological alterations. First, an AKI phase (day 5) was demonstrated as attested by a significant increase in plasma creatinine along with PTEC necrosis as well as proteinuria. Later, during the progression of AKI to CKD, increased in oxidative stress and inflammatory cell infiltration (macrophages and lymphocytes) were characterized. Finally, chronic phase (day 20) was characterized by an extensive tubular atrophy and a massive tubulo-interstitial fibrosis as attested by Red Sirius staining and increased in pro-fibrotic gene expression.

Conclusion

AKI-to-CKD transition has clinical importance since patients surviving an episode of AKI present a significant risk of progression to CKD. However, the mechanisms by which AKI might initiate the CKD onset have not been fully defined. A better understanding of these mechanisms could lead to identify key biomarkers as well as new therapeutic strategies to prevent and treat AKI or impede progression to CKD. In this regard, animal models of AAN could represent a useful tool to provide important insights into the underlying mechanisms of AKI-to-CKD transition.

Funding

  • Government Support - Non-U.S.