Cardiopulmonary Bypass and the Kidney: New Evidence for Old Foes.

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Published in final edited form as: Anesthesiology. 2025 May 13;142(6):985–988. doi: 10.1097/ALN.0000000000005464 Cardiopulmonary Bypass and the Kidney: New Evidence for Old Foes Natalie A Silverton 1, 2 , Guillaume L Hoareau 3 , Kai Kuck 4 Author information Article notes Copyright and License information 1 University of Utah Department of Anesthesiology, Helix Building 5050, 30N Mario Capecchi Dr., Salt Lake City, UT 84132 2 Geriatric Research, Education, and Clinical Center, VA Medical Center, 500 Foothill Dr, Salt Lake City, UT 84148 3 Nora Eccles Harrison Cardiovascular Research and Training Institute, Department of Emergency Medicine, Helix Building 5050, 30 N Mario Capecchi, Room 2S240, Level 2, South, Salt Lake City, Utah 84132 4 University of Utah Department of Anesthesiology, Helix Building 5050, 30N Mario Capecchi Dr., Salt Lake City, UT 84132 ✉ Corresponding Author: Natalie A. Silverton, natalie.silverton@hsc.utah.edu Roles Natalie A Silverton : MD FRCPC , Associate Professor Guillaume L Hoareau : PhD DVM FCCM , Assistant Professor Kai Kuck : PhD , Professor Issue date 2025 Jun 1. PMC Copyright notice PMCID: PMC12077602  NIHMSID: NIHMS2067700  PMID: 40358330 The publisher's version of this article is available at Anesthesiology See " Persistent Renal Hypoxia and Histologic Changes at 4 Weeks after Cardiopulmonary Bypass in Sheep " on page 1047. Acute kidney injury (AKI) is a devastating complication of cardiac surgery, affecting 25–40% of patients and significantly impacting mortality. 1 – 5 Understanding the risk for AKI is straightforward: these are often elderly patients with multiple comorbidities undergoing major surgery with significant blood loss, hemodynamic changes, and vasoactive medication administration. We have all suspected, however, that the particularly elevated risk of AKI in cardiac surgery patients is also related to the use of cardiopulmonary bypass (CPB). In this month’s issue of Anesthesiology , Furukawa et al. present compelling evidence that CPB is indeed a significant factor, initiating changes in kidney oxygenation and structural kidney injury that persist for weeks post-surgery. (ref original article) This work comes from a team of Australian investigators who have studied kidney hypoxia in critical illness for decades. Rinaldo Bellomo explored the complicated relationship between norepinephrine and kidney perfusion in his 2001 review Noradrenaline and the kidney: friends or foes . 6 Later, Yugeesh Lankadeva, Clive May, Roger Evans, Rinaldo Bellomo, and colleagues developed a pivotal large animal model with real-time measurements of kidney oxygen concentration and tissue perfusion. They showed that, during sepsis, norepinephrine raises blood pressure, improves urine output, and decreases serum creatinine, yet renal medullary hypoxia worsens. 7 In other words, administering norepinephrine might provide a false sense of security, as traditional indicators of kidney function normalize while kidney oxygenation continues to deteriorate. Adapting their animal model to cardiac surgery, this same group has demonstrated that renal medullary oxygen concentration significantly decreases with the initiation of CPB. 8 , 9 In this latest study, Furukawa et al. have made it evident that CPB-induced kidney hypoxia is not the transient insult we might wish it to be. Indeed, the reduction first in renal medullary and then in cortical tissue oxygen concentration was sustained for up to 4 weeks post-CPB. (ref original article) Furthermore, at 4 weeks, animals exposed to CPB showed more histological evidence of structural kidney injury than controls. Notably, conventional markers of AKI, such as serum creatinine concentration and urine output, did not change significantly. Five of the 8 sheep were diagnosed with KDIGO Stage I AKI based on urine output criteria only, with no change in serum creatinine concentration from baseline. Thus, other than a transient dip in urine output, these animals showed no evidence of AKI based on traditional markers yet had persistent decreases in kidney oxygenation and evidence of structural kidney injury. One limitation of the study is the lack of sufficient power to determine a direct association between kidney tissue hypoxia and structural injury. A more extensive study with varied duration of kidney hypoxia and histological assessment would be needed. However, conducting such a large study with prolonged survival would be extremely expensive and difficult. Readers might also argue that the changes in oxygenation and histology found in this study are not important because serum creatinine concentration, the standard for AKI diagnosis, was unchanged. We must remember, however, that serum creatinine concentration is only a marker of glomerular filtration rate (GFR). Analogous to ejection fraction as a measure of cardiac function, GFR is a functional indicator that only becomes compromised after a significant degree of structural damage has occurred. We would never dismiss a patient with chest pain simply because an echocardiogram showed a normal ejection fraction. For the heart, we have real-time monitors of cardiac ischemia (EKG) and serum markers of cardiac ischemia (troponins). For the kidney, serum and urinary biomarkers of structural injury have been developed and validated in cardiac surgery patients, but the technology is prohibitively expensive and is not readily available as a point-of-care tool. 10 – 12 When structural kidney injury was measured in cardiac surgery patients using urinary biomarkers, patients with subclinical AKI (biomarker positive but serum creatinine negative) had an increased risk of requiring dialysis or in-hospital mortality. 13 Thus, kidney hypoxia and structural injury likely matter even without serum creatinine elevation. The study by Furukawa et al. suggests that to improve kidney outcomes in cardiac surgery, we must turn our attention to developing real-time markers of kidney hypoxia and determining what interventions can improve kidney oxygenation. Placing oxygen sensors in cardiac surgery patients is prohibitively invasive, but over a decade ago, Roger Evans and colleagues envisioned urine oxygen concentration as “ a clinical window on the health of the renal medulla .” 14 Since then, this group has pioneered the use of urine oxygen as a real-time monitor of kidney hypoxia, showing a correlation between urine oxygen and medullary oxygen in animals and an association between intraoperative urine oxygen and AKI after cardiac surgery. 7 , 15 – 18 As for effective intervention, Lankadeva et al. demonstrated that increasing bypass pump flows and MAP improves renal medullary oxygenation. 8 , 9 In humans, higher pump flows reduced oxygen extraction and increased urine oxygen concentration. 19 18 Systemic oxygen delivery during CPB is primarily a function of bypass pump flow and the availability of hemoglobin for oxygen transport. Ranucci et al. found that targeting a systemic oxygen delivery of ≥ 280 ml/min/m2 decreased AKI risk. 20 These studies suggest that optimizing perfusion during CPB might mitigate kidney hypoxia and subsequent AKI risk. Unfortunately, the answer to improving kidney oxygenation likely will not be as easy as just maintaining higher bypass pump flows and raising hemoglobin concentration. Pump flows are limited by cannula size and concern for vessel wall injury and hemolysis. 21 Although anemia is associated with AKI after cardiac surgery, so is blood transfusion. 22 , 23 Blood conservation techniques like ultrafiltration have been implicated in increasing risk for AKI, not reducing risk. 24 , 25 Thus, investigation into novel strategies to improve kidney oxygenation is needed in order to prevent kidney hypoxia during CPB, and individualized therapy based on real-time kidney hypoxia monitoring may be required to prevent AKI. The authors of the current study should be commended for their model, which represents a significant advancement in the study of renal pathophysiology during and after CPB. Developing a large-animal model with long-term invasive measurements is an exceptionally challenging endeavor, requiring meticulous surgical techniques, prolonged post-operative management, and advanced instrumentation. The difficulty of executing such a model cannot be overstated, as it demands both technical precision and extensive resources. Despite these challenges, the authors have successfully executed a study that enhances our mechanistic understanding of cardiac surgery-associated AKI and opens the door for future investigation. This study by Furukawa et al. underscores the critical role of CPB in inducing sustained kidney hypoxia and structural injury, which traditional markers of AKI may fail to detect. This research highlights the need for real-time monitoring of kidney oxygenation and the development of novel interventions to mitigate renal injury during cardiac surgery. Future studies should focus on refining noninvasive monitors of kidney hypoxia and exploring targeted therapies to improve kidney oxygenation. The goal is to provide individualized hemodynamic management in the operating room and intensive care units aimed at reducing the incidence of AKI. The work presented by Furukawa et al. advances our understanding of the effects of CPB on kidney hypoxia and structural injury, providing a solid foundation for these future studies and a basis for continued innovation in this field. Funding Statement: Dr. Silverton is supported by an International Anesthesiology Research Society Mentored Research Grant and through funding from the Geriatric Research, Education, and Clinical Center at the Salt lake City VA Medical Center. Dr. Hoareau is supported by grants from the Department of Defense (HT9425-1-0140), the Nora Eccles Treadwell Foundation, and NIH/NHLBI (1R01HL170196-01, 1R01HL163145-01, and 1R43HL176331). Footnotes Disclosure Statement: Drs. Silverton and Kuck are co-inventors on a patent for a noninvasive urine oxygen and flow sensing technology. This prototype has not been commercialized nor do the authors have the license to commercialize this technology as the intellectual property belongs to the University of Utah. Dr. Hoareau is a consultant and shareholder of Certus Critical Care. Contributor Information Natalie A. Silverton, University of Utah Department of Anesthesiology, Helix Building 5050, 30N Mario Capecchi Dr., Salt Lake City, UT 84132; Geriatric Research, Education, and Clinical Center, VA Medical Center, 500 Foothill Dr, Salt Lake City, UT 84148. Guillaume L. Hoareau, Nora Eccles Harrison Cardiovascular Research and Training Institute, Department of Emergency Medicine, Helix Building 5050, 30 N Mario Capecchi, Room 2S240, Level 2, South, Salt Lake City, Utah 84132. Kai Kuck, University of Utah Department of Anesthesiology, Helix Building 5050, 30N Mario Capecchi Dr., Salt Lake City, UT 84132. References 1. Bastin AJ, Ostermann M, Slack AJ, Diller GP, Finney SJ, Evans TW. Acute kidney injury after cardiac surgery according to Risk/Injury/Failure/Loss/End-stage, Acute Kidney Injury Network, and Kidney Disease: Improving Global Outcomes classifications. J Crit Care. 2013;28(4):389–96. Epub 2013/06/08. doi: 10.1016/j.jcrc.2012.12.008. [ DOI ] [ PubMed ] [ Google Scholar ] 2. Howitt SH, Grant SW, Caiado C, Carlson E, Kwon D, Dimarakis I, Malagon I, McCollum C. The KDIGO acute kidney injury guidelines for cardiac surgery patients in critical care: a validation study. BMC Nephrol. 2018;19(1):149. Epub 2018/06/27. doi: 10.1186/s12882-018-0946-x. 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Epub 20150722. doi: 10.1016/j.athoracsur.2015.04.120. [ DOI ] [ PubMed ] [ Google Scholar ] ACTIONS View on publisher site PDF (45.6 KB) Cite Collections Permalink RESOURCES Similar articles Cited by other articles Links to NCBI Databases Follow NCBI NCBI on X (formerly known as Twitter) NCBI on Facebook NCBI on LinkedIn NCBI on GitHub NCBI RSS feed Connect with NLM NLM on X (formerly known as Twitter) NLM on Facebook NLM on YouTube National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 Web Policies FOIA HHS Vulnerability Disclosure Help Accessibility Careers NLM NIH HHS USA.gov Back to Top

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