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Kidney Week

Abstract: TH-PO111

Kinetics of the De Novo NAD/NADH Pathway from AKI to CKD

Session Information

  • AKI: Mechanisms - I
    November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Serre, Justine, INSERM UMRS 1155, Paris, France
  • Bras, Alexandre, INSERM UMRS 1155, Paris, France
  • Galichon, Pierre, INSERM UMRS 1155, Paris, France
  • Hadchouel, Juliette, INSERM UMRS 1155, Paris, France

Group or Team Name

  • CoRaKiD UMRS_1155.
Background

Energy metabolism deficiency is part of the acute kidney injury (AKI) pathophysiology. Recent studies highlighted the role of nicotinamide adenine dinucleotide (NAD) production in the pathogenesis of AKI. NAD is an electron carrier for mitochondria and a cofactor for cytoplasmic redox reactions. Its production is decreased during AKI following a decrease of the expression of PGC1α (Peroxisome proliferator activated receptor gamma co-activator-1-α) and an alteration of its de novo synthesis pathway: with a reduction in the expression of the Quinolinate PhosphoRibosylTransferase (QPRT). The modulation of this de novo pathway has been studied mainly in the acute phase immediately after AKI. However, its correlation with the severity of the ischemic insult and its evolution during the transition from AKI to CKD have not been described yet.

Methods

Renal ischemia-reperfusion was performed in C57Bl6/J male mice after nephrectomy of the contralateral kidney. For the 'severity' study, a 5-30 minutes ischemia was performed. Renal function was assessed 24h after ischemia. For the 'AKI to CKD' study, renal ischemia was performed during 10 minutes. Mice were sacrificed 1, 2, 3, 6 and 28 days after ischemia. PGC1α and QPRT mRNA expression was measured by RT-qPCR.

Results

We induced AKI in mice by unilateral ischemia reperfusion injury of increasing time to induce several degrees of AKI severity. PGC1α and QPRT mRNA expression decreased progressively with ischemia severity until reaching a plateau at 15 minutes of ischemia for PGC1α, like plasma creatinine and urea, whereas QPRT decrease is linear until 30 min of ischemia. PGC1α mRNA decrease is also inversely correlated to kidney dysfunction (p<0.001).
A 10-minute ischemia led to the development of Chronic Kidney Disease (CKD), as evidenced by an incomplete recovery of the kidney function at 28 days. QPRT and PGC1α mRNA expression showed a progressive but incomplete recovery during the transition from AKI to CKD compared to sham mice.

Conclusion

In addition to confirming the decrease of PGCα and QPRT mRNA expression during AKI, we show that it is correlated to the severity of the ischemic AKI. Furthermore, we describe the recovery during renal repair and transition to CKD.

Funding

  • Government Support – Non-U.S.