Kidney Week

Abstract: TH-PO220

Oxalate Cardiotoxicity in CKD

Session Information

• Hypertension and CVD: Basic Research Findings
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1601 Hypertension and CVD: Basic

Authors

• Jaber, Karim, NYU Langone Health, New York, New York, United States

Karim Jaber, MD, MS, MSc

• Xiong, Xiaozhong, NYU Langone Health, New York, New York, United States

Xiaozhong Xiong, MD

• Merritts, Kyle, NYU Langone Health, New York, New York, United States

Kyle Merritts

• Akosah, Yaw A., New York University College of Dentistry, New York, New York, United States

Yaw A. Akosah, MSc, PhD

• Pavlov, Evgeny, New York University College of Dentistry, New York, New York, United States

Evgeny Pavlov, PhD

• Nazzal, Lama, NYU Langone Health, New York, New York, United States

Lama Nazzal, MD, MS, MSc

Background

Cardiovascular (CV) events are the leading cause of death among patients with chronic kidney disease (CKD), yet the underlying mechanisms remain poorly understood. Oxalate retention could significantly contribute to CVD in this population. Mitochondrial damage stands out as a potential mechanism of oxalate-induced toxicity, given its association with CKD-induced cardiac damage and oxalate nephrotoxicity.
We hypothesize that oxalate-enriched diet increases plasma oxalate levels, induces CV toxicity and mitochondria dysfunction.

Methods

H9C2 cardiomyocytes were cultured and treated with 0, 50, 100 and 250 uM of sodium oxalate (NaOx) for 48 hrs. Mitochondrial function was evaluated via the Seahorse assay, and mitochondrial morphology and membrane potential were assessed through staining.
12 5/6 nephrectomy (CKD) mice were administered either a 1% sodium oxalate supplemented normal chow (NC) or NC for three months. Plasma samples were collected for oxalate and creatinine measurements. Histology and mitochondrial imaging were performed on the heart tissue at sacrifice.

Results

In vitro studies demonstrated that sodium oxalate induces mitochondrial dysfunction in a dose-dependent matter.
Mice from both dietary groups showed a comparable degree of CKD at sacrifice but abnormal mitochondrial morphology was observed in the hearts of these oxalate fed mice, when compared to their controls.

Conclusion

Oxalate induces cardiotoxicity, possibly through mitochondrial damage.