Impact of Cardiopulmonary Bypass Flow on Renal Oxygenation, Blood Flow and Tubular Injury

Study Overview
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Brief Summary
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During open cardiac surgery, cardiopulmonary bypass (CPB) is used to temporarily replace the function of the heart and lungs. Renal ischemia resulting in acute kidney injury is common after cardiac surgery. The renal oxygenation is impaired during CPB, but the oxygenation may be improved by increasing the CPB blood flow. In this randomized study, two CPB flow rates will be compared regarding renal outcome (biomarkers and renal oxygenation/renal blood flow), as well as markers of inflammation and hemolysis. Additionally, urine oxygen tension will be measured during CPB and the early intensive care phase and compared to renal oxygenation. Regional oxygen saturation assessed with near infrared spectroscopy from the brain and kidneys will be monitored during and after surgery.

Official Title
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Impact of Cardiopulmonary Bypass Flow on Renal Oxygenation, Blood Flow and Tubular Injury

Conditions
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Renal Failure, Extracorporeal Circulation; Complications, Circulation Disorder, Renal Plasma Flow, Effective, Cardiopulmonary Bypass, Hemolysis, Inflammatory Response

Intervention / Treatment
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* Procedure: High CPB flow


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written, signed informed consent Male and female subjects ≥18 years Left ventricular ejection fraction ≥30 % Estimated GFR ≥30 ml/min using the CKD-EPI equation (Levey 2009) Scheduled open cardiac surgery with CPB Planned normothermia during CPB Expected CPB time > 60 minutes Exclusion Criteria: Emergency surgery Cardiac transplantation Advanced grown-up congenital heart disease corrections Previous cerebral infarction, verified with computed tomography or magnetic resonance imaging Body mass index > 32 kg/m2 Use of hypothermia < 32 °C during CPB Inability of the patient to give based opinion In the investigator´s opinion, the patient has a condition that could be adversely affected by study participation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: To compare normal (2.4 L/min/m2) and high (2.9 L/min/m2) cardiopulmonary bypass flow during cardiac surgery
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Normal CPB flow<br>In this group, the target flow during cardiopulmonary bypass (CPB) will be 2.4 L/min/m2 throughout the CPB period. | |
| Experimental: High CPB flow<br>In this group, the target flow during cardiopulmonary bypass (CPB) will be 2.9 L/min/m2 throughout the CPB period. | Procedure: High CPB flow<br>* Target CPB flow 2.9 L/min/m2 throughout the CPB period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker u-NAG | Tubulus injury biomarker N-acetyl-ß-d-glucoseaminidase (NAG) will be analyzed in urine with a spectrophotometric method and corrected for urine creatinine. | 24 hours | 
| Biomarkers Nephrocheck | Renal biomarker assay Nephrocheck (IGFBP-7 x TIMP-2) will be analyzed in urine | 24 hours | 
| Renal oxygen delivery and blood flow | Renal oxygen delivery during and after cardiopulmonary bypass (CPB) | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum creatinine and acute kidney injury (AKI) | Changes in serum creatinine | 48 hours | 
| Inflammation IL-1 | Differences in inflammatory marker IL-1 | 24 hours | 
| Inflammation IL-6 | Differences in inflammatory marker IL-6 | 24 hours | 
| Inflammation IL-8 | Differences in inflammatory marker IL-8 | 24 hours | 
| Inflammation IL-10 | Differences in inflammatory markers IL-1, IL-6, IL-8, IL-10 and TNFa | 24 hours | 
| Inflammation TNFa | Differences in inflammatory marker TNFa | 24 hours | 
| Complement activation | Differences in complement activation | 24 hours | 
| Hemolysis | Differences in markers of hemolysis (free plasma Hb, LD, haptoglobin) | 24 hours | 
| Erythropoetin | Differences in serum-erythropoietin | 24 hours | 
| Neuroinflammation Tau | Changes in Tau | 4 days | 
| Neuroinflammation NF | Changes Neurofilament | 4 days | 
| Kidney function | Measured glomerular filtration rate (iohexol clearance) on postoperative day 1 | 24 hours | 
| Renal function | Measured glomerular filtration rate by iohexole clearance on the first postoperative day | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal oxygenation, renal blood flow, cardiopulmonary bypass, tubular cell injury, N-acetyl-beta-D-glucosaminidase, nephrocheck, inflammation, hemolysis