Sims-Lucas Laboratory Research Finds Dicarboxylic Acid Supplementation Shown to Prevent Acute Kidney Injury in Preclinical Study
December 5, 2023
A new study by the Sims-Lucas Laboratory in the Division of Pediatric Nephrology at UPMC Children's Hospital of Pittsburgh explored the potential of dicarboxylic acids (DCAs), particularly octanedioic acid (DC8), in preventing acute kidney injury (AKI).
The study will be published in the January 2024 edition of the Journal of the American Society of Nephrology (JASN) and was selected by the journal as its cover article feature for this edition.
Sunder Sims-Lucas, PhD, associate professor of Pediatrics was the study’s senior author. The research is part of his ongoing efforts at probing the basic mechanisms at play in acute kidney injury, particularly around fatty acid oxidation.
“As nephrologists and critical care medicine specialists are painfully aware, AKI is a critical health concern carrying significant rates of morbidity and mortality,” says Dr. Sims-Lucas. “And, we still have no approved treatments or therapeutics to combat the disorder outside of evidence-based supportive care measures.”
Study Summary and Important Findings
AKI often results from various stresses like ischemia, physical trauma, or exposure to various nephrotoxic medications, for example, certain cancer-fighting therapeutics. The kidneys, especially the proximal renal tubule cells, are highly dependent on the energy produced from fatty acid oxidation (FAO). This process predominantly occurs in mitochondria. However, the kidneys also have peroxisomes, another cell organelle, which can undertake a similar FAO process.
This study from the Sims-Lucas lab team explored how shifting FAO from the mitochondria to the peroxisomes potentially could be protective against AKI. They specifically looked at DC8 and another DCA, DC12, two medium-chain fatty acids, and how they affected FAO in a small animal model of AKI.
In the study, the subjects were fed diets supplemented with DC8 or DC12. They were then subjected to models simulating AKI.
“We found that both DC8 and DC12 prevented the increase of AKI markers, but the animals given DC8 showed more substantial protection against AKI than did the DC12 cohort,” says Dr. Sims-Lucas.
The kidneys of DC8-fed mice showed extensive succinylation of proteins related to peroxisomal activity, indicating a shift from mitochondrial to peroxisomal FAO.
What makes this discovery notable is the potential for a new therapeutic approach to a condition that has limited treatment options. The use of DC8, a supplement that can be easily administered and is cost-effective, opens possible new approaches for not only managing AKI but also potentially preventing it in high-risk scenarios.
The findings from the Sims-Lucas lab’s study provide a foundation for future investigations into the clinical application of DC8 for AKI treatment and prevention.
Learn more about Dr. Sims-Lucas and his laboratory in the Division of Pediatric Nephrology at UPMC Children’s Hospital of Pittsburgh.
Reference
Barbosa ACS, Pfister KE, Chiba T, Bons J, Rose JP, Burton JB, King CD, O’Broin A, Young V, Zhang B, Sivakama B, Schmidt AV, Uhlean R, Schilling B, Goetzman ES, Sims-Lucas S. Dicarboxylic Acid Supplementation Protects From Acute Kidney Injury Via Stimulation of Renal Peroxisomal Activity. J Am Soc Nephrol. 2022 Dec 4. Online a
