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In silico deceased donor intervention research: A potential accelerant for progress.

Mark J Hobeika^1,2,3,4,5, Stefano Casarin^3,6,5, Ashish Saharia^1,2,3,5

¹J.C. Walter, Jr. Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, Texas.

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons

|January 4, 2021

Summary

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Developing an in silico model of deceased donor physiology aids research into kidney donor interventions. This computational tool simulates donor injury, guiding the testing of new therapeutic strategies.

Area of Science:

Computational biology
Organ transplantation research
Physiological modeling

Background:

Research into interventions for deceased organ donors is limited.
In silico models can identify therapeutic targets and streamline intervention testing for deceased donors.

Purpose of the Study:

To develop and validate a preliminary in silico model of deceased kidney donor injury.
To assess the model's ability to simulate pathophysiological changes and intervention effects.

Main Methods:

The in silico model was constructed using data from published animal and human studies.
Model calibration and validation were performed against existing research findings.
Simulations included assessing hemodynamic, oxygenation, cytokine, and inflammatory markers.

Keywords:

basic (laboratory) research/science clinical research/practice cytokines/cytokine receptors donors and donation: deceased kidney biology mathematical model organ transplantation in general

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The model's response to therapeutic hypothermia was evaluated.

Main Results:

The in silico model accurately replicated animal study findings on brain death pathophysiology and renal injury markers.
The model successfully simulated the effects of therapeutic hypothermia, mirroring clinical trial outcomes.
The model demonstrated utility in predicting upstream markers of renal injury.

Conclusions:

The developed in silico model serves as a foundational tool for understanding deceased kidney donor physiology.
This model can accelerate the investigation of novel interventions for deceased donors.
Further development is needed to create a clinically applicable computational model for organ donor management.