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Ex Vivo Red Blood Cell Hemolysis Assay for the Evaluation of pH-responsive Endosomolytic Agents for Cytosolic Delivery of Biomacromolecular Drugs
Published on: March 9, 2013
Exploring carboxyhemoglobin as a predictive marker of hemolysis-related CSA-AKI
Sara Terrenghi1, Baptiste Duceau1, Pauline Dureau1
1Sorbonne Université, GRC 29, Assistance Publique-Hôpitaux de Paris (AP-HP), DMU DREAM, Département d'anesthésie et réanimation, Institut de Cardiologie, Hôpital La Pitié-Salpêtrière, F-75013 Paris, France.
Insights
Immediate postoperative carboxyhemoglobin (COHb) effectively predicts cardiac surgery-associated acute kidney injury (CSA-AKI). This biomarker indicates hemolysis intensity, aiding in identifying high-risk patients for targeted renal protection.
Area of Science:
- Nephrology
- Cardiology
- Biomarker Discovery
Background:
- Cardiac surgery-associated acute kidney injury (CSA-AKI) is a frequent complication post-cardiopulmonary bypass (CPB).
- Hemolysis is a key pathophysiological factor in CSA-AKI.
- The role of carboxyhemoglobin (COHb) as a hemolysis biomarker for CSA-AKI requires further characterization.
Purpose of the Study:
- To evaluate carboxyhemoglobin (COHb) as a predictive biomarker for CSA-AKI.
- To compare the performance of COHb against other hemolysis biomarkers.
- To assess the association between COHb levels and CSA-AKI severity and outcomes.
Main Methods:
- Prospective observational study of 262 adult patients undergoing on-pump cardiac surgery.
- Measurement of postoperative COHb, methemoglobin, lactate dehydrogenase (LDH), and total bilirubin.
- CSA-AKI assessment using KDIGO criteria; statistical analysis including ROC and multivariable logistic regression.
Main Results:
- 32.8% of patients developed CSA-AKI.
- COHb demonstrated superior discriminative performance for CSA-AKI (AUC 0.65) compared to other biomarkers.
- Postoperative COHb independently predicted CSA-AKI and was associated with increased AKI severity and mechanical ventilation duration.
Conclusions:
- Immediate postoperative COHb is a promising predictor of CSA-AKI.
- COHb levels reflect CPB-related hemolysis intensity.
- COHb can identify patients at higher risk for hemolysis-related CSA-AKI, guiding renal-protective strategies.
Background:
Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most frequent complications after cardiopulmonary bypass (CPB), in which hemolysis plays an important pathophysiological role. Carboxyhemoglobin (COHb) plays a key role in metabolism and heme turnover, but its value as a hemolysis-related biomarker of CSA-AKI has not been fully characterized.
Methods:
We conducted a single-centre, prospective observational study in adults undergoing on-pump cardiac surgery for a 4-month period. The primary objective was to assess the performance value of COHb to predict CSA-AKI and to compare it with other hemolysis-related biomarkers. COHb, methemoglobin, lactate dehydrogenase (LDH), and total bilirubin were evaluated in the immediately postoperatively. CSA-AKI was assessed according to the KDIGO criteria.
Results:
Among 262 included patients, 86 (32.8%) developed CSA-AKI. In ROC analysis, COHb showed the best discriminative performance for CSA-AKI (AUC 0.65, 95% CI 0.58-0.72), compared with methemoglobin, total bilirubin, and LDH. An optimal COHb cut-off of 1.25% yielded a sensitivity of 0.58 and a specificity of 0.65. In multivariable logistic regression, immediate postoperative COHb remained independently associated with CSA-AKI (odds ratio 1.89, 95% CI 1.02-3.49), together with age, preoperative atrial fibrillation, and CPB duration. Higher COHb levels (≥1.25%) were associated with increased incidence and severity of AKI and longer mechanical ventilation, but not with vasopressor duration, ICU length of stay, ICU mortality, or postoperative atrial fibrillation. COHb correlated positively with CPB duration.
Conclusions:
Immediate postoperative COHb is a potential predictor of CSA-AKI and reflects the intensity of CPB-related hemolysis. COHb may serve as a biomarker to identify patients at higher risk of hemolysis-related CSA-AKI and to guide targeted renal-protective strategies after cardiac surgery.
