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Abstract: SA-PO103

Deficiency of Long-Chain Acyl-CoA Dehydrogenase (LCAD) Protects Against AKI

Session Information

  • AKI: Mechanisms - III
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Chiba, Takuto, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Goetzman, Eric S., University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Sims-Lucas, Sunder, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States

Acute kidney injury (AKI) is caused by distinct etiologies including renal ischemia/ reperfusion injury (IRI) and nephrotoxins such as cisplatin. Proximal tubular epithelial cells (PTECs) are particularly vulnerable to such injuries, owing to high energy demands. While fatty acids are the preferred energy source for PTECs via fatty acid oxidation (FAO), FAO-mediated H2O2 production in mitochondria has been shown to be a major source of oxidative stress in multiple diseases, including AKI. We have previously shown that mitochondrial flavoprotein long-chain acyl-CoA dehydrogenase (LCAD), which catalyzes a key step in mitochondrial FAO, directly produces H2O2 in vitro. However, the role of LCAD during AKI has yet to be determined.


LCAD deficient mice (-/-) and wild-type controls (+/+) were both derived from a common breeding pair of LCAD heterozygous deficient mice (+/-). Western blot analysis confirmed loss of LCAD expression in LCAD-/- kidneys. Male mice age 10-14 weeks were subjected to two distinct AKI models: 1. renal IRI (18 min ischemia) or 2. Single high dose cisplatin (24 mg/ kg bw. i.p.). The kidneys were monitored by histologic evaluation (H&E staining) and serum chemistry. Female mice age 10-14 weeks were also subjected to the high-dose cisplatin-AKI model (20 mg/ kg bw. i.p.).


LCAD deficiency does not cause any overt change in renal histology or function in the absence of injury. However, following renal IRI or cisplatin treatment, age- and sex-matched LCAD-/- kidneys demonstrated protected kidney function (limited BUN/ creatinine increase) and less tissue injury when compared with controls. This was coupled with inhibited mitochondrial FAO. Additionally, LCAD-/- mice showed that mitigated reduction of serum albumin or bicarbonate following AKI.


LCAD deficiency confers protection against two distinct models of AKI in a sex independent manner. This suggests a therapeutically attractive mechanism whereby decreased mitochondrial FAO mediates protection against AKI.


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