Markers of kidney tubule dysfunction and injury and long-term risk of acute kidney injury following coronary artery bypass graft surgery
Lauren Shingler, Ashutosh Tamhane, Ching-Min Chu, Jennifer A. Frey, Emily B. Levitan, Suzanne E. Judd, Alexander L. Bullen, Edward D. Siew, Joseph V. Bonventre, Michael G. Shlipak, Byron Jaeger, Jesse C. Seegmiller, Alexander Keister, Henry E. Wang
Abstract
Approximately one in five patients undergoing coronary artery bypass graft (CABG) surgery will develop post-operative acute kidney injury (AKI). We sought to determine whether biomarkers of kidney tubule dysfunction and injury are associated with long-term risk of acute kidney injury (AKI) after coronary artery bypass graft (CABG) surgery.
Introduction
Acute kidney injury (AKI) is a major global public health problem, affecting 13−18 million patients and contributing to 1.5–1.7 million deaths worldwide each year [1]. In the United States alone, AKI accounts for $10 billion in additional healthcare expenditures per year [2].
Materials and methods
The parent REasons for Geographic and Racial Disparities in Stroke (REGARDS) study and this ancillary study were approved by the Institutional Review Board of the University of Alabama at Birmingham.
Results
Among the 30,239 REGARDS participants, 760 (2.5%) underwent CABG surgery [17]. We excluded 366 participants with illegible or incomplete records, 3 participants for a history of hemodialysis use or kidney transplant at hospital admission.
Discussion
Our study builds upon our prior research from the SPRINT blood pressure trial, where we found that biomarkers of kidney tubular dysfunction (A1M, UMOD, EGF), but not injury, were associated with future development of AKI in a subgroup of CKD patients [6,18–21].
Conclusion
Biomarkers of tubule health, measured in community-based adults at a stable phase of health, are associated with AKI events after future CABG surgery. This finding was stronger for markers of kidney tubule dysfunction than for markers of tubule injury.
Citation: Shingler L, Tamhane A, Chu C-M, Frey JA, Levitan EB, Judd SE, et al. (2026) Markers of kidney tubule dysfunction and injury and long-term risk of acute kidney injury following coronary artery bypass graft surgery. PLoS One 21(6): e0331996. https://doi.org/10.1371/journal.pone.0331996
Editor: Ramada Rateb Khasawneh, Yarmouk University, JORDAN
Received: August 25, 2025; Accepted: April 28, 2026; Published: June 1, 2026
Copyright: © 2026 Shingler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: REGARDS data are not publicly available due to ethical and legal restrictions. To abide by its obligations with NIH/NINDS and the Institutional Review Board of the University of Alabama at Birmingham, REGARDS facilitates data sharing through data use agreements. Any investigator is welcome to access the REGARDS data, including statistical code, through this process. Requests for data access may be sent to regardsadmin@uab.edu.
Funding: This work was supported by award R01-DK128803 from the National Institute of Diabetes and Digestive and Kidney Diseases. The parent REGARDS study was supported by cooperative agreement U01-NS041588 from the National Institute of Neurological Disorders and Stroke (NINDS) and National Institute on Aging (NIA), National Institutes of Health (NIH), Department of Health and Human Services (DHHS). Additional funding was provided by R01-HL080477 and R01-HL165452 from the National Heart Lung and Blood Institute (NHLBI), and R37-DK39733, R01-DK072381 and U01-DK085660 provided by the National Institute of Diabetes and Digestive and Kidney Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS or the NIA. Representatives of the NINDS were involved in the review of the manuscript but were not directly involved in the collection, management, analysis or interpretation of the data. The authors thank the other investigators, the staff, and the participants of the REGARDS study for their valuable contributions. A full list of participating REGARDS investigators and institutions can be found at: REGARDS Investigators and Institutions.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: AKI, acute kidney injury; CKD, chronic kidney disease; ESRD, end-stage renal disease; A1M, alpha-1 microglobulin; UMOD, uromodulin; EGF, epidermal growth factor; KIM-1, kidney injury molecule-1; CABG, coronary artery bypass graft; CS, cohort study; SCr, serum creatinine
