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Abstract: TH-PO100

PGC1α in Complex Models of AKI

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Tran, Mei T., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Parikh, Samir M., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States

Acute kidney injury (AKI) in patients is often complex, arising in the context of background chronic kidney disease (CKD) or even recent AKI from a different etiology. In experimental models of simple AKI, we have identified a critical role for the mitochondrial biogenesis regulator PPAR-γ coactivator-1α (PGC1α) in resistance to and recovery from AKI. Renal PGC1α expression is markedly reduced in both septic and post-ischemic mice. And PGC1α knockout (KO) mice suffer worse renal function and overall survival after transient renal ischemia, whereas PGC1α induction in the renal tubule improves AKI recovery and survival. The potential role for PGC1α in a more translatable “multi-hit” experimental model of AKI, however, remains unexplored.


1st AKI insult: PGC1α KO and WT mice underwent 15 minutes of bilateral renal ischemia. Serum creatinine measurements were collected at 24 hours, 1 month, and 6 months after ischemia reperfusion injury (IRI).

2nd AKI insult: Six months following the initial renal IRI, mice were administered cisplatin (intraperitoneal, 10 mg/kg), then monitored for 72 hours post-injection.


PGC1α KO mice exhibited increased serum creatinine relative to WT littermates at 24 hours after IRI. At 1 month and 6 months post-IRI, creatinine in both genotypes had recovered to normal levels. However, 6-month survival in KO mice was 83% compared to 100% survival in WT mice. Within 48 hours of the second AKI insult, survival was 33% in KO versus 75% in WT.


PGC1α may impact both kidney function and overall survival after AKI. Despite KO survivors of the initial AKI insult recovering to indistinguishable and normal serum creatinine as compared to control littermates, PGC1α KO mice suffered worse outcomes after the second insult. The results suggest that PGC1α, and by extension mitochondrial homeostasis, may have important effects on the renal response to cumulative insults. Given the increasingly appreciated connections between AKI and CKD, models of repeated AKI may illuminate mechanisms of transition from acute insult to chronic impairment.


  • NIDDK Support