From the Guidelines
Yes, acute kidney injury (AKI) after cardiopulmonary bypass can indeed be due in part to complement activation from the bypass circuit. The most recent and highest quality study, published in 2025 1, provides guidelines for kidney protection during cardiopulmonary bypass in adult cardiac surgery, but does not directly address the role of complement activation. However, it recommends strategies to reduce AKI, such as maintaining adequate perfusion pressure and considering the perioperative use of intravenous N-acetylcysteine in patients with chronic kidney disease.
When blood comes into contact with the artificial surfaces of the cardiopulmonary bypass (CPB) circuit, it triggers the complement cascade, particularly through the alternative pathway. This activation leads to the formation of inflammatory mediators like C3a and C5a, which cause neutrophil activation, increased vascular permeability, and direct tissue injury. The resulting systemic inflammatory response can cause renal vasoconstriction, reduced renal blood flow, and tubular damage, all contributing to AKI.
Key strategies to mitigate this risk include:
- Using heparin-coated circuits to reduce complement activation
- Minimizing bypass duration to reduce exposure to the circuit materials
- Maintaining adequate perfusion pressure during CPB to ensure renal perfusion
- Proper perioperative fluid management to ensure adequate renal perfusion
- Considering modified ultrafiltration techniques to remove inflammatory mediators after bypass, although the use of excessive ultrafiltration (>30 ml kg−1) during CPB is not recommended due to the increased risk of postoperative AKI, as reported in a study published in 2024 1.
Understanding this mechanism helps explain why AKI remains a common complication after cardiac surgery despite improvements in CPB technology. The 2019 guidelines on cardiopulmonary bypass in adult cardiac surgery also emphasize the importance of maintaining adequate perfusion pressure and oxygen delivery during CPB to reduce the risk of AKI 1.
From the Research
Possible Causes of AKI after Cardiopulmonary Bypass
- The exact cause of AKI after cardiopulmonary bypass is multifactorial and not fully understood 2, 3.
- Several mechanisms have been proposed, including compromised perfusion and oxygenation, inflammatory activation, oxidative stress, coagulopathy, hemolysis, and endothelial damage 3.
- Hemoglobin-induced renal injury may be a major contributor to CPB-associated AKI, suggesting that AKI after CPB may be a form of pigment nephropathy 4.
Role of Complement Activation
- There is no direct evidence in the provided studies to suggest that complement activation from the bypass circuit is a contributing factor to AKI after cardiopulmonary bypass.
- However, inflammatory activation is mentioned as a possible mechanism of AKI after CPB, which may involve complement activation 3.
Prevention and Treatment of AKI after Cardiopulmonary Bypass
- Current interventions aimed at preventing and attenuating renal impairment related to CPB include optimizing CPB by adjusting equipment parameters, optimizing surgical procedures, or using improved materials to mitigate kidney damage 3.
- Employing pharmacological or interventional measures targeting pathogenic factors, such as sodium bicarbonate infusion to prevent hemoglobin-induced pigment nephropathy, may also be beneficial 4.
- Maintenance of adequate renal perfusion pressure and avoidance of fluid overload, with consideration of early renal replacement therapy, are also recommended 2.