Before surgery, the anesthesia team will meet with a patient to determine the optimal and safest way to keep them comfortable during their procedure.  

Answers to questions on past medical history, to medications and supplements and lifestyle choices like whether they smoke or drink alcohol are carefully considered and any risk factors that could complicate the procedure or subsequent recovery are proactively addressed. 

But what if the patients’ own genes could help guide anesthesia and surgical care?

This is the unique question posed by Nicholas Douville, M.D., Ph.D., of the Department of Anesthesiology and colleagues. 

Their overall goal is to use precision medicine to deliver better care around the time of surgery.

Previous work, funded by the National Institute of Diabetes and Digestive and Kidney Diseases attempted to understand why some patients develop acute kidney injury after surgery while others don't.  

The team looked for associations between specific genes and kidney injury using patient data from biobanks at U-M (Michigan Genomics Initiative) and Vanderbilt University (BioVU).

Genetic risk was quantified and incorporated with traditional factors to calculate a patient’s unique risk profile.

Genome-wide association studies on samples from biobanks from U-M and Vanderbilt did not identify strong associations between specific genes and  postoperative acute kidney injury, cardiac surgery associated acute kidney injury, or sepsis-associated acute kidney injury. 

Furthermore, established clinical risk factors played a much larger role in determining who developed acute kidney injury. 

But before counting out the influence of genetics, Douville and team turned to a much larger data set—the All of Us Research Program, sponsored by the National Institutes of Health, designed to build a diverse database to inform a variety of health conditions.

“The All of Us Research Program has a special focus on engaging participants that have been previously underrepresented in biomedical research,” said Douville. 

“So, it offered us an opportunity to explore the question of perioperative outcomes in a more diverse population than we’ve studied in the past.”

This is especially important because acute kidney injury disproportionately impacts Black patients, yet studies in institutional biobanks, such as the Michigan Genomics Initiative, lacked the ancestral diversity to fully explore this racial disparity. 

To date, All of Us has enrolled about 850,000 participants, and has often been used to examine questions about chronic diseases. 

In a report in JAMA Surgery, Douville, along with Miklos D. Kertai, M.D., Ph.D., of Vanderbilt and Kyle Sheetz, M.D., of U-M Health, propose two novel tools that leverage the All of Us dataset to look at acute health events such as surgery.

“With perioperative complications, temporal relationships become very important.   First you have to figure out whether the patient had any evidence of this condition before surgery and then you have to resolve which process of care may have contributed to the complication,” said Douville.

Their algorithm allows researchers to map and classify surgical procedures from the dataset. Another application, he noted, could be emergency medicine research into the intersection of genes and emergent health conditions and subsequent ICU admission and outcomes. The tools are free and downloadable algorithms he hopes will be employed by other researchers in the perioperative space to further define surgical complications.

“Genetics is one of many factors that we're trying to incorporate into an overall pursuit of precision medicine,” said Douville. 

Funding/disclosures: Research in this paper was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases (1 K08 DK131346-02). 

All of Us Research Program: The All of Us Research Program is supported by the National Institutes of Health, Office of the Director: Regional Medical Centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA #: AOD 16037; Federally Qualified Health Centers: HHSN 263201600085U; Data and Research Center: 5 U2C OD023196; Biobank: 1 U24 OD023121; The Participant Center: U24 OD023176; Participant Technology Systems Center: 1 U24 OD023163; Communications and Engagement: 3 OT2 OD023205; 3 OT2 OD023206; and Community Partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276. In addition, the All of Us Research Program would not be possible without the partnership of its participants.

Paper cited: “Expanding the All of Us Research Platform into the Perioperative Domain through Reusable Methods for Defining Surgical Populations and Postoperative Acute Kidney Injury,” JAMA Surgery. DOI: 10.1001/jamasurg.2024.2343 

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