Plasma nuclear and mitochondrial DNA are associated with post-traumatic acute kidney injury




Assistant Professor of Medicine

Project Summary

This summer I worked closely with Dr. Michael Shashaty and Caitlin, the clinical research coordinator of his lab, in the Pulmonary, Allergy & Critical Care Division within the School of Medicine. One of the main topics that Dr. Shashaty’s lab focuses on is acute kidney injury (AKI) in critical illness populations. An abrupt decline in kidney function, AKI can lead to serious complications if not detected early or treated properly. Nuclear and mitochondrial DNA (nDNA, mtDNA), which are damage-associated molecular patterns (DAMPs) released from damaged tissues after trauma, may contribute to AKI. However, studies in trauma patients remain limited. Over the past few years, Dr. Shashaty’s lab has enrolled trauma patients into his AKI study and has collected and analyzed the patients’ blood samples. Now, as the project proceeds, we are looking to clarify whether plasma nDA and mtDNA would be associated with post-traumatic AKI.

Throughout the summer, I learned about and experienced multiple steps of the clinical research process. The first step was screening. I became familiar with a computerized database and several electronic medical record systems. Every morning, I checked the list of patients presented to the trauma bay the day before, reviewed their medical charts, identified the mechanism and timing of trauma, and assigned each patient an Injury Severity Score (ISS) based on injuries by body regions. Then, I screened patients based on specific inclusion and exclusion criteria. For those patients who got enrolled, I assisted in data entry to expand a dataset of their medical history, ER, OR, and ICU data. Furthermore, I helped obtain and process time-sensitive blood and urine specimens from the ICU. What I learned and enjoyed the most was AKI phenotyping. Specifically, I learned how to identify AKI status for each enrolled patient throughout her hospitalization based on her serum creatine level. I was able to locate the timepoints at which the patient first met the criteria and at which the highest stage was first observed in order to construct a detailed timeline of the patient’s AKI status. The final step was data analysis. Together with Dr. Shashaty and biostatistician Dr. Yang, we constructed mixed effects models, adjusting for trauma mechanism, ISS, transfusions, and shock, to test associations of mtDNA and nDNA levels from presentation to 48 hours with AKI.

Besides assisting clinical research, I had the opportunity to shadow physicians in ICU rounds where I could observe how a team of physicians, nurses, respiratory therapists, and dietitians work together and interact with patients and their families to provide the best care possible. I also joined one of the chest X-ray reading sessions during which patients with acute respiratory distress syndrome (ARDS) were identified.

From this summer experience working with Dr. Shashaty, I gained clear insights into the workings of clinical research, in which ingenious planning, frequent updates, and multidisciplinary collaboration are emphasized and valued. Driven by my reinforced passion for healthcare and growing interest in acute illness, I look forward to continuing working with Dr. Shashaty in the future.