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. 2025 Jun 1;142(6):1047-1057.
doi: 10.1097/ALN.0000000000005452. Epub 2025 Mar 19.

Persistent Renal Hypoxia and Histologic Changes at 4 Weeks after Cardiopulmonary Bypass in Sheep

Taku Furukawa  1 , Clive N May  2 , Alemayehu H Jufar  1 , Roger G Evans  3 , Andrew D Cochrane  1 , Bruno Marino  4 , Peter R McCall  5 , Ian E Birchall  6 , Sally G Hood  1 , Jaishankar Raman  7 , Connie P C Ow  1 , Anton Trask-Marino  1 , Rinaldo Bellomo  8 , Lachlan F Miles  9 , Yugeesh R Lankadeva  9
Affiliations

Persistent Renal Hypoxia and Histologic Changes at 4 Weeks after Cardiopulmonary Bypass in Sheep

Taku Furukawa et al. Anesthesiology. .

Abstract

Background: The sustained renal effects of exposure to cardiopulmonary bypass are unknown. This study aimed to test whether cardiopulmonary bypass (CPB) is associated with sustained renal tissue hypoxia and whether such hypoxia is associated with histologic injury.

Methods: The study included 12 adult female sheep undergoing CPB with a 2-h aortic cross-clamp. Systemic and renal hemodynamics and oxygen delivery, kidney function, and renal tissue oxygenation were measured before and during CPB, in the 48 h after CPB, and weekly for 4 weeks. The sheep were euthanized at 4 weeks and obtained renal tissue to perform histopathologic assessments for comparison with an independent cohort of five healthy animals that were euthanized without undergoing surgical or experimental interventions. These histologic assessments were performed by an independent, treatment-blinded pathologist.

Results: Compared with baseline, renal blood flow and renal medullary tissue oxygenation decreased significantly during CPB. In the first 48 h after CPB, there was a continuing significant decrease in medullary tissue oxygenation (from 39.2 ± 13.8 mmHg at baseline to 21.7 ± 16.2 mmHg at 48 h; Ptime = 0.006) with stage 1 acute kidney injury in 42% of the animals. Moreover, in the following 4 weeks, medullary (16.1 ± 12.9 mmHg at 4 weeks; Ptime = 0.005) and cortical (17.2 ± 6.5 mmHg at 4 weeks; Ptime = 0.005) tissue oxygenation remained significantly lower than baseline. Finally, compared with healthy sheep, at 4 weeks after CPB, sheep kidneys had significantly more peritubular inflammation (8 of 8 vs . 1 of 5; P = 0.007), interstitial fibrosis (6 of 8 vs . 0 of 5; P = 0.021), and tubular casts (8 of 8 vs . 1 of 5; P = 0.007).

Conclusions: Exposure to CPB triggers sustained medullary and cortical tissue hypoxia and is associated with histopathologic renal injury. These findings suggest that the renal effect of exposure to CPB may be more profound and longer lasting than currently appreciated.

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Conflict of interest statement

Dr. Miles has served on a medical advisory committee for BD Advanced Patient Monitoring (formerly Edwards Lifesciences) in an unpaid capacity within the last 5 yr; the work performed as part of this committee is unrelated to this article. The other authors declare no competing interests.

Figures

Fig. 1.
Fig. 1.
Schematic description of experimental timeline. Created with BioRender.com. CPB, cardiopulmonary bypass.
Fig. 2.
Fig. 2.
Changes in renal tissue oxygenation and hemodynamics in the initial 48 h post-CPB. (A) Renal medullary tissue oxygen tension (tPo2). (B) Cortical tPo2. (C) Renal blood flow. (D) Renal vascular conductance. (E) Renal oxygen delivery. (F) Renal venous oxygen saturation. Sample size is indicated on each panel, because some of the data are missing due to equipment failure. The data were subjected to mixed-effects model with a Greenhouse–Geisser correction applied to the main effect of “time.” The data are presented as means and SD. CPB, cardiopulmonary bypass.
Fig. 3.
Fig. 3.
Changes in renal macro- and microcirculation from 1 to 4 weeks post-CPB. (A) Renal medullary tissue oxygen tension (tPo2). (B) Cortical tPo2. (C) Renal oxygen delivery. Sample size is indicated on each panel, because some of the data are missing due to equipment failure or loss of subjects. The data were subjected to a mixed-effects model with a Greenhouse–Geisser correction applied to the main effect of “time.” The data are presented as means and SD. CPB, cardiopulmonary bypass.
Fig. 4.
Fig. 4.
Representative images of histologic analysis. (A, B) Normal kidney tissue. (C, D) Mild and moderate peritubular inflammation. (E, F) Mild and moderate interstitial fibrosis. (G) Hyaline casts. (H) Cellular casts. White bars represent 50 µm.
See this image and copyright information in PMC

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