Perioperative Nitric Oxide Prevents Acute Kidney Injury in Acute Type A Aortic Dissection Patients

The incidence of acute kidney injury following acute type A aortic dissection is significantly high, thereby exerting a substantial impact on patient prognosis. Nitric oxide, an endogenous gaseous molecule with potential therapeutic effects, has been investigated in clinical studies as a treatment for acute kidney injury following cardiac surgery. However, there is currently no clinical study exploring the application of nitric oxide in patients with acute type A aortic dissection. Therefore, this study aims to investigate whether exogenous nitric oxide therapy has renal protective effects and its mechanism.

This prospective randomized study is conducted at Beijing Anzhen Hospital in Beijing, China. A total of 106 adult patients with acute type A aortic dissection are enrolled in this study. The patients are randomly divided into two groups: the experimental group received NO combined with conventional treatment, and the control group is only given conventional treatment. In the experimental group, 60 ppm NO is administered during intraoperative CPB and continued until within 12 hours after surgery.

The primary endpoint is the incidence of acute kidney injury (AKI) within 48 hours after surgery. The secondary endpoints include AKI grade (KDIGO); urine volume during CPB, within 12 and 24 hours after surgery; blood flow grade, resistance index, and pulsatility index in renal ultrasound at ICU admission, 12 and 24 hours after surgery; SOFA score at 24 hours after surgery; VIS score at ICU admission, 12 and 24 hours after surgery; duration of mechanical ventilation, non-invasive ventilation, and high-flow oxygen therapy; length of ICU stay and hospital stay; renal adverse events within 90 days; volume of drainage from the pleural and pericardial cavities after surgery. Additionally, dosage of diuretics and recombinant human brain natriuretic peptide during surgery and within 48 hours after surgery; oxygenation index and near-renal infrared oxygen saturation; levels of free hemoglobin, methemoglobin, nitrite (NO2-) and the total of NO metabolites (NOt); neutrophil gelatinase-associated lipocalin concentration; levels of the neutrophils lymphocytes ratio (NLR), the platelet lymphocyte ratio (PLR), systemic inflammatory response index (SIRI), and systemic immune response index (SII) ; CVP and PEEP, the volume of transfusions with plasma and stored or autologous RBCs will also be measured in both groups.

Inclusion criteria

• Provide written informed consent;
• Participants must be over 18 years of age;
• Participants should meet the diagnostic and treatment guidelines for thoracic aortic diseases jointly issued by ACC/AHA in 2022, have received clinical and radiological diagnosis of acute type A aortic dissection, and undergone surgical thoracotomy within two weeks after symptom onset.

Exclusion criteria

• Missing baseline value or missing postoperative serum creatinine value (Scr);
• Preoperative eGFR less than 30ml/min/1.73m2 or receive renal replacement therapy;
• History of kidney disease, including glomerular diseases: acute glomerulonephritis, rapidly progressive glomerulonephritis, chronic glomerulonephritis, nephrotic syndrome, etc., secondary nephropathy: lupus nephritis, diabetic nephropathy, interstitial nephritis, renal tubular disease, chronic renal failure, renal replacement therapy, etc.;
• Previous renal tumor, kidney transplantation, and other related surgery;
• Patients with single kidney;
• History of malignant tumor or received radiotherapy and chemotherapy;
• Severe skeletal muscle disease and autoimmune disease;
• Preoperative dissection rupture or hemodynamic instability (systolic blood pressure <90mmHg);
• Life expectancy less than 90 days;
• Pregnant and lactating women, patients with mental disorders;
• With intravascular or extravascular hemolytic disease;
• Have participated in other clinical trials.