Metabolomics Analysis of Acute Kidney Injury and Delirium After Cardiac Surgery: Single Center, Prospective, Observational Study

Approximately 2 million patients undergo cardiac surgery every year, of which approximately 20% to 30% experience cardiac surgery related acute kidney injury (CSA-AKI). At least 3% of CSA-AKI patients require temporary renal replacement therapy, and approximately 25% of patients will develop chronic kidney disease2 in three years. Several retrospective cohort studies have reported a significant correlation between AKI related to cardiac surgery and subsequent occurrence of chronic kidney disease, end-stage renal disease, heart failure, and major cardiovascular adverse events. Meanwhile, the occurrence of CSA-AKI is significantly associated with higher hospitalization costs and increased short-term and long-term postoperative mortality rates, with 5-year and 7-year cohort survival rates of 54% and 38%, respectively.

The pathogenesis of CSA-AKI is complex, caused by various potential kidney damage during the perioperative period. The commonality of these injuries is that the oxygen delivery into the kidneys is lower than the oxygen demand of the kidneys, leading to renal tubular injury. Hypothetical mechanisms leading to CSA AKI include hypoperfusion 8, atherosclerotic embolism, toxic effect of nephrotoxin 9, inflammation and oxidative stress hypothesis 1, etc. The hemodynamic changes, reduced oxygen supply, inflammation, and oxidative stress caused by these mechanisms may all lead to AKI10. In view of the high incidence rate of CSA AKI and its potentially devastating sequelae, it is urgent for clinical staff to understand how to best prevent and mitigate CSA-AKI.

Due to special reasons such as large surgical trauma, high surgical stress, extracorporeal circulation, and the need to be transferred to the cardiovascular intensive care unit after surgery, the incidence of postoperative delirium in the heart and large blood vessels (PODOCVS) is as high as 26% to 52%. PODOCVS refers to an acute neurological disorder that occurs after surgery, mainly characterized by confusion in thinking, decreased spatial and temporal positioning abilities. Related studies suggest that PODOCVS significantly prolongs patients' mechanical ventilation time, ICU stay time, incidence of complications, and is closely related to long-term cognitive decline and increased long-term mortality. However, the mechanism research of PODOCVS is still in its initial stage. Existing research has shown that multiple factors such as surgical trauma, extracorporeal circulation, and intraoperative management work together to cause neural network dysfunction through various mechanisms and pathways, leading to the occurrence of PODOCVS. The neuroinflammation theory plays a crucial role in the pathogenesis of PODOCVS. Acute peripheral inflammation stimulation induces the expression of inflammatory factors (IL-6, IL-8, IL-1 β α, TNF - α) in the central nervous system, leading to neuronal synaptic dysfunction, hippocampal dependent memory damage, and subsequent behavioral and cognitive symptoms. Some scholars have also proposed that damage to the anatomical structure and functional abnormalities of the central nervous system are potential mechanisms of PODOCVS. Through head magnetic resonance imaging of 116 patients undergoing elective cardiac surgery, it was found that the decrease in gray matter volume may be related to delirium during surgery. PODOCVS has many adverse effects on patient prognosis, therefore its mechanism research is crucial for the correct prevention and management of PODOCVS.

Clinical evidence suggests that renal injury leads to changes in the structure of the cerebral cortex in patients, suggesting the existence of the renal brain axis. Therefore, some scholars have proposed that AKI may be an important cause of secondary injuries such as delirium. Approximately 60% of AKI patients in clinical practice experience delirium. Elevated creatinine levels>2mg/dL are one of the risk factors for ICU delirium in elderly patients. Renal replacement therapy can reduce the risk of AKI related delirium. For patients receiving renal replacement therapy, daily peak serum creatinine is not related to delirium, but may reduce the impact of AKI on the brain by clearing neurotoxic metabolites. This suggests that renal function has a significant impact on cognitive function in patients, and the gradual normalization of renal function may improve delirium.

Although the underlying mechanism associated with acute renal injury and delirium is still unclear, it has become a consensus that it increases incidence rate and mortality, prolongs hospital stay, and accelerates long-term cognitive decline . The pathogenesis of AKI related delirium is multifactorial, and several hypotheses have been proposed regarding the pathogenesis of AKI induced delirium, including the hypothesis of accumulation of neurotoxins or delirium inducing drugs due to impaired renal clearance function, the hypothesis of upregulation of systemic cytokine mediated neuroinflammatory processes, and the hypothesis of volume overload leading to brain edema.