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Kidney Week

Abstract: TH-PO027

Mitochondrial Dysfunction in an In Vitro and an In Vivo Model of Aristolochic Acid Nephropathy

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Mosseray, Pauline, University of Namur, NAMUR, Belgium
  • Jadot, Inès, University of Namur, NAMUR, Belgium
  • Pierre, Louise, University of Namur, NAMUR, Belgium
  • Juszczak, Florian, UMONS, Mons, Belgium
  • Botton, Olivia, University of Namur, NAMUR, Belgium
  • Nortier, Joelle L., Hospital Erasme, Brussels, Belgium
  • Arnould, Thierry, University of Namur, NAMUR, Belgium
  • Decleves, Anne-Emilie, UMONS, Mons, Belgium
  • Caron, Nathalie, University of Namur, NAMUR, Belgium

Mitochondrial (mt) dynamics is a key player during AKI and CKD. Indeed, mt provide energy to cells thereby supporting many cellular processes. They are of high importance in kidneys, more specifically regarding proximal tubular epithelial cells (PTEC). Aristolochic Acid Nephropathy (AAN) is a rapidly progressive tubulointerstitial nephritis characterized by necrosis of PTEC. In these cells, mt play a major role since PTEC ensure reabsorption and secretion functions. Our study aimed to investigate the mt dysfunction during AAN using both C57Bl/6 male mice and HK-2 cells.


C57Bl/6 male mice were divided into CTL or AA groups. AA groups received four ip injections of AAI (3.5 mg/kgBW) from D1 to D4 and were sacrificed at D4, D5 and D10. The mt ultrastructure’s were analyzed by TEM while kidney function and structure were assessed by BUN, plasma and urinary creatinine, GFR and histological analysis. For the in vitro part, confluent HK-2 cells (human PTEC) were exposed to AAI at 0, 1, 10 or 25 µM during 24h, 48h or 72h. FACS and confocal analysis were performed to analyze the mt abundance and network as well as the cellular granularity. Moreover, cellular ATP contents were quantified.


During progression of AAN in mice, structural damages in mt, consisting in the loss of mt cristae and/or contents, were observed, attesting the loss of their integrity and morphology. These observations were concomitant with AAN progression and development of AKI, as shown by a significant increase in BUN and plasma creatinine as well as a significant decrease of GFR. Moreover, at day 10, mt were either absent or only observable as mt debris in necrotic cells where the population of mt exhibiting alterations was increased in remaining cells. During AA-intoxication in HK-2 cells, the fragmentation of mt network and an increase of cellular granularity were observed throughout the protocol while an increase of mt abundance was reported at three days of AA-intoxication, concomitant with a decrease of ATP contents.


We demonstrated the impairment of mt morphology and network during AA-intoxication in both models. Regarding the data, proteins involved in fusion and fission process must be investigated in order to identify molecular actors that may lead to mt dysfunction.