Objective: Measures that capture aging-related decline can identify patients at risk for cardiac surgery-associated adverse events to guide perioperative care and improve patient outcomes. We determined if a panel of biomarkers of cellular senescence, a fundamental aging mechanism, can predict risk of adverse kidney and cardiac events in patients undergoing CABG surgery. Methods: Patients to undergo CABG with or without valve repair or replacement were recruited into a pilot cohort of 66 patients and a development cohort of 331 patients. Blood samples were collected prior to surgery for assessment of expression of preselected biomarkers of senescence. Patients were followed through hospital stay and up to a 30d post-surgery. Daily post-op serum creatinine (sCR) was used to identify incidence of acute kidney injury (AKI) and sCr measures at 30 days were used to identify patients whose eGFR decreased 25% or more as compared to baseline (development cohort only). A composite of major adverse cardiac and kidney events (MACKE30) was used as another endpoint in development cohort only. Results: AKI occurred in 30.0% of patients in pilot study and 19.9% of development cohort. Persistent decline in kidney function at 30d occurred in 11.0%, and MACKE30 in 13.4% of patients. A panel of six biomarkers of senescence (p16, p14, LAG3, CD244, Cd28 and suPAR) were able to identify patients at risk for AKI (AUC 0.76), kidney decline at 30d (AUC 0.73), and MACKE30 (AUC 0.71). When compared between top and bottom tertiles of senescence-based risk models, patients in the top tertile had 7.8 (3.3-8.4) higher odds of developing AKI, 4.5 (1.6-12.6) higher odds of developing renal decline at 30d, and 5.7 (2.1-15.6) higher odds of developing MACKE30. All models remained significant when adjusted for clinical variables Surprisingly, patients with kidney function decline and AKI were largely non-overlapping, and potentially of different etiology. Typical clinical factors that predispose to AKI (e.g., age, CKD, surgery type) associated with AKI but not the 30d decline endpoint. Instead, a new-onset atrial fibrillation associated with 30d kidney decline and not AKI. Conclusions: A 6-member panel of biomarkers of senescence, a fundamental mechanism of aging, can identify patients for risk of adverse kidney and cardiac events when measured pre-operatively.

The authors have declared no competing interest.

This work was funded in part by grants from the NIH/NIA (R43AG050353 and R44AG060888). The funding sources had no involvement in the study design or in the collection, analysis and interpretation of data. The funding sources also had no involvement in the writing of this report or in the decision to submit the report for publication.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRB of Johns Hopkins University, Duke University, and Central IRB (WIRB/WCG) overseeing WakeMed Health and Hospitals and Hoag Memorial Hospital Presbyterian gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Due to the informed consent and data privacy policies, the clinical data are not publicly available, i.e., accessible for anyone, for any purpose without a review by the Central IRB on a project-by-project basis. Requests for raw data can be made to the corresponding author.