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Kidney Week

Abstract: TH-PO107

Role of Kynurenine/Tryptophan Ratio in Kidney-Lung Cross-Talk in Two Porcine Trauma-Induced Multi-Organ Injury Models

Session Information

  • AKI: Mechanisms - I
    November 03, 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

Authors

  • Singh, Pragya, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Montemayor, Daniel, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Pamreddy, Annapurna, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Drel, Viktor, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Ye, Hongping, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Franzone, Anthony J., The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Zang, Yanyi, Autonomous Reanimation and Evacuation Research Program, San Antonio, Texas, United States
  • Roberts, Teryn R., Autonomous Reanimation and Evacuation Research Program, San Antonio, Texas, United States
  • Chung, Kevin K., Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States
  • Batchinsky, Andriy, Autonomous Reanimation and Evacuation Research Program, San Antonio, Texas, United States
  • Sharma, Kumar, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
Background

Multiple Organ Failure (MOF), often precipitated by Acute Respiratory Distress Syndrome (ARDS) brought on by trauma-induced injury, is a significant cause of death in military and civilian life. In ARDS, Acute Kidney Injury (AKI) is the most common organ failure, affecting nearly half of all patients and having twice the mortality rate than those with ARDS alone. Thus, understanding the molecular differences between survivors and non-survivors can significantly reduce the mortality burden.

Methods

A 24-hour unilateral pulmonary contusion porcine model (pneumonectomy) of trauma-induced MOF model (n=17) and separate 48-hour polytrauma injury of bilateral pulmonary contusion, traumatic brain injury, and hemorrhage (polytrauma) MOF model (n=26) was developed at Dr. Batchinsky's AREVA laboratory. Serum was assayed at baseline and 3h or 6h post-trauma for amino acid metabolites using the Zip-Chip platform for mass spectrometry. The IDO1 enzyme activity assay kit (ab235936) was used to measure IDO1 enzyme activity in the tissue.

Results

In the pneumonectomy model, 10 survived and 7 died and in the polytrauma group, 13 survived and 13 died. In the pneumonectomy model, there was a significant increase in the serum kynurenine/tryptophan (KYN/TRP) ratio in the non-survivors 3h post-injury. A similar pattern was found in the validation group, which showed a significant increase in the KYN/TRP ratio at 6h post-trauma in non-survivors from the polytrauma model. There was a significant increase in IDO1 enzyme activity in non-survivor kidney tissues and no changes in the lungs in the pneumonectomy model.

Conclusion

In two separate ARDS multi-organ injury trauma porcine models, an increase in the KYN/TRP ratio post-trauma identified the pigs that suffered early mortality. The increase in kidney IDO1 activity could contribute to the reduction in serum tryptophan and increase in kynurenine in the non-survivors. As a result, focusing on therapeutics targeting the kynurenine pathway to reduce the incidence and severity of MOF is warranted.

Funding

  • Other U.S. Government Support