cfDNA Biomarkers in Lung Transplantation

Lung transplantation is a life-saving therapy for patients with end-stage lung diseases, yet the demand for donor lungs far exceeds availability. A major reason for this shortage is the low utilization of donor lungs, especially those colonized by multidrug-resistant (MDR) bacteria. Although up to 70% of donor lungs test positive for bacterial pathogens, most are declined out of concern for post-transplant infection, rejection, or poor survival. This cautious approach often leads to the loss of otherwise viable lungs.

At King Faisal Specialist Hospital and Research Centre (KFSH&RC), it has been recently shown that donor lungs with MDR bacteria do not always result in worse outcomes, except in cases involving specific pathogens such as Klebsiella pneumoniae and Stenotrophomonas maltophilia. These findings suggest that a more precise and timely tool is needed to assess lung tissue injury, rather than rejecting donor lungs based solely on bacterial cultures.

This project introduces plasma cell-free DNA (cfDNA) as a novel biomarker for evaluating lung quality in donors with MDR bacteria. cfDNA consists of short DNA fragments released into the bloodstream during tissue injury, providing a sensitive, non-invasive measure of organ damage. By analyzing total and lung-specific cfDNA levels, the project aims to:

1. Differentiate between true bacterial infections, harmless colonization, and negative cultures.

2. Identify cfDNA profiles linked to high-risk pathogens.

3. Predict early post-transplant outcomes and guide donor selection.

In collaboration with the National Heart, Lung, and Blood Institute (NHLBI, USA), this study will utilize advanced cfDNA technologies capable of distinguishing injury across specific lung compartments, such as alveolar and vascular tissues.

If successful, cfDNA profiling will provide clinicians with a rapid, accurate, and non-invasive tool to determine donor lung quality in real time. This breakthrough could expand the donor pool, reduce waiting list mortality, and improve transplant outcomes by ensuring that suitable lungs are not discarded unnecessarily.

By combining clinical insights with cutting-edge molecular diagnostics, this research aligns with Saudi Arabia’s Vision 2030 health innovation priorities and has the potential to position the Kingdom as a leader in transplant precision medicine. The project is funded by Saudi NIH (2025).