Background:
The sustained renal effects of exposure to cardiopulmonary bypass (CPB) are unknown. We aimed to test whether CPB is associated with sustained renal tissue hypoxia and whether such hypoxia is associated with histological injury.
Methods:
We studied 12 adult female sheep undergoing CPB with a 2-h aortic cross-clamp. We measured systemic and renal hemodynamics and oxygen delivery, kidney function, and renal tissue oxygenation, before and during CPB, in the 48 h after CPB, and weekly for four weeks. We euthanized the sheep at four weeks and obtained renal tissue to perform histopathological assessments for comparison with an independent cohort of five healthy animals that were euthanized without undergoing surgical or experimental interventions. These histological 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 (AKI) in 42% of 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 post-CPB sheep kidneys had significantly more peritubular inflammation (8/8 vs. 1/5, P = 0.007), interstitial fibrosis (6/8 vs. 0/5, P = 0.021) and tubular casts (8/8 vs. 1/5, P = 0.007).
Conclusions:
Exposure to CPB triggers sustained medullary and cortical tissue hypoxia and is associated with histopathological renal injury. These findings suggest that the renal effect of exposure to CPB may be more profound and longer lasting than currently appreciated.