CI-AKI is a common complication associated with the use of iodinated contrast media in various imaging procedures, such as computed tomography (CT), angiography, and intravenous urography. It is a significant clinical concern due to its association with increased morbidity, prolonged hospital stays, and higher healthcare costs [1] . At present, using physiological saline for hydration therapy is a commonly used clinical approach, but recent studies have shown that sodium bicarbonate may become a new option. Some drugs (statins, antioxidants) and remote ischemic preconditioning also have a certain role in preventing the occurrence of CI-AKI.

This article elaborates on CI-AKI from five aspects: definition, epidemiology, risk factors, pathogenesis, and clinical prevention.

We conducted extensive searches in databases such as Pubmed, Google Scholar, and SCI, with the main keywords being “AKI”, “CIN”, CI-AKI, “contrast agent”, etc. Two reviewers independently reviewed the eligibility of each article.

Contrast-induced acute kidney injury was previously most commonly defined as a 25% or more increase in serum creatinine from baseline, or an absolute increase of 0.5 mg/dl or more, 48 - 72 hours after exposure to contrast agents [2] . According to Kidney Diseases: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines, contrast-induced acute kidney injury is defined as an increase in creatinine levels of ≥0.3 mg/dl (26.5 μmol/l) from baseline within 48 hours after contrast exposure, or an increase of at least 1.5 times baseline within 7 days, or urine output below 0.5 mL/kg body weight/hour, sustained for at least 6 hours after exposure. And the severity level was graded based on urine output and serum creatinine levels [3] .

Acute kidney injury (AKI) causes 2 million deaths per year and is commonly found in hospitals [4] . Relevant studies have shown that hospital-acquired AKI accounts for 22% of all AKI cases globally, while CI-AKI is the third most common cause of AKI in hospitalized patients [5] . The incidence of CI-AKI varies widely between studies (2% - 15%), depending on the definition criteria and patient population, and up to 9% of patients with CI-AKI may require dialysis; In any case, the severity of CI-AKI appears to be strongly associated with the primary clinical outcome. In-hospital mortality was reported to be 7.1% in patients with less severe CI-AKI and 35.7% in patients with AKI requiring dialysis. In addition, in a retrospective analysis of 27,608 patients treated with CA, the greater the absolute or relative increase in creatinine, the greater the risk of adverse clinical outcomes [6] . In the ICU, the increasing use of CT imaging and interventional surgery means that more patients will be exposed to intravascular iodized contrast agents. At the same time, patients are critically ill and have varying degrees of organ function impairment, which increases the risk of contrast-induced AKI [7] . Patients with CI-AKI are more likely to experience adverse events, including more hospital stays and costs, longer ICU stays, and higher mortality [1] .

Chronic renal insufficiency is often considered the most important risk factor. According to reports, the incidence of CI-AKI is 55% higher in patients with previous chronic kidney disease who receive standard percutaneous coronary intervention, possibly due to decreased adaptability but also increased cell exposure [8] . If the same amount of CM is filtered with fewer nephrons, the exposure of individual nephrons will significantly increase proportionally [9] .

Aging is associated with changes in renal structure and functional decline, indicating a higher incidence of CI-AKI in elderly patients. According to a 2014 observational study, 5 out of 13 patients over 65 years old developed CI-AKI (38.46%), while patients under 65 years old did not [10] . CI-AKI is defined as an increase of 25% or more from Scr baseline, or an absolute increase of 0.5 mg/dL, until the fifth day after contrast agent infusion.

The results of numerous related studies have confirmed that contrast agent dosage is often one of the important factors in CI-AKI. The given contrast dose is directly related to the incidence of CI-AKI. For example, in the study by Garvan C Kane et al. [11] , it was found that the volume of patients with CI-AKI (45 ± 18 ml) was higher than that of patients without CI-AKI (31 ± 18 ml, p < 0.0005); Compared to patients with the highest quartile of contrast agent volume, patients with the lowest quartile of contrast agent volume are 7 times less likely to develop CI-AKI. In other reports, it was also pointed out that the incidence of CI-AKI was 2.4% in patients receiving higher CM volumes, while 0.18% in patients receiving volumes lower than the maximum calculated CM dose [12] . In addition, the osmotic pressure and viscosity of contrast agents may also play a certain role in the occurrence of CI-AKI [13] .

Long term use of non steroidal anti-inflammatory drugs (NSAIDS), aminoglycoside drugs, vancomycin, amphotericin B, immunosuppressive drugs (such as cyclosporine), and loop diuretics may also increase the risk of CI-AKI, and it is necessary to avoid using them for a short period of time before and after imaging as much as possible [14] .

Diabetes nephropathy is a common chronic complication of diabetes, and diabetes nephropathy is an independent risk factor for chronic kidney disease (CKD) and CI-AKI. Contrast agents can rapidly alter renal hemodynamics, leading to hypoxia and ischemia. High glucose status is a promoting factor of CI-AKI, which can enhance oxidative stress and increase ROS on the one hand; On the other hand, it can lead to dysfunction of vasoactive substances, stronger renal vasoconstriction, and insufficient oxygen supply. It will also increase the load on some ion pumps and increase oxygen consumption [15] .

Genetic susceptibility is also a potential risk factor. The overview of CI-AKI pathogenesis suggests that various genes act collectively, generating either a favorable or harmful environment of pro- and anti-inflammatory cytokines, which determines the intensity of tissue damage. The most relevant genes are those related to the systemic inflammatory response [16] .

The pathophysiology of contrast-induced acute kidney injury is complex and involves many different mechanisms [17] . Current studies have shown that contrast agent-related acute kidney injury occurs mainly through two mechanisms: hypoxia damage to renal parenchyma (especially medullary hypoxia) and toxic effects of contrast agent on renal capillaries and tubules [18] [19] .

Hypoxia and subsequent ischemia-reperfusion injury lead to a large number of oxidative products dominated by ROS and form oxidative stress, resulting in abnormal activity of proteins and enzymes, structural changes and functional damage of DNA, and lipid damage [20] . The toxicity of contrast agents mainly targets renal vascular endothelial cells and renal tubular epithelial cells, leading to increased apoptosis and necrosis [21] . Specific molecular mechanisms may include damage to organelles by contrast agents through cell membranes, mitochondrial damage, efficiency of respiratory chain reduction, release of cytochrome, and induction of apoptosis through the mitochondrial pathway [22] . Another round of oxidative stress from ROS follows after mitochondrial damage. Contrast agents affect renal microcirculation, leading to hypoxia and ischemia-reperfusion injury, followed by renal tissue damage and excess ROS production. At the same time, contrast agents have toxic effects on renal tubular epithelial mitochondria and vascular endothelium, mediating mitochondrial apoptosis pathway. ROS is a central part of this [15] .

In conclusion, CI-AKI is a significant clinical challenge that requires a multifaceted approach to prevention and management. Understanding the risk factors, pathophysiology, and current best practices is essential for healthcare providers to optimize patient care and improve outcomes in those undergoing contrast-enhanced imaging procedures. The occurrence of CI-AKI may lead to a significant decrease in the quality of life of patients. Due to the acute decline in renal function, patients may experience a series of symptoms such as fatigue, loss of appetite, nausea, and vomiting. From a long-term health perspective, CI-AKI may lead to a sustained decline in renal function, develop into chronic kidney disease, and even require long-term dialysis treatment, which not only increases medical costs but may also lead to a shortage of medical resources. The use of physiological saline for hydration therapy is still the best preventive strategy, and more clinical trials are still needed to use sodium bicarbonate as a hydration regimen. Treatment methods such as statins and long-term ischemic preconditioning have a certain positive effect on preventing CI-AKI. Antioxidants (such as vitamin C, vitamin E, and NAC) can also be considered as a new clinical prevention strategy. At the same time, when using contrast agents, it is necessary to use them as little as possible.

The authors declare no conflicts of interest regarding the publication of this paper.

Li, X. and Liu, Q. (2024) A Systematic Review of Contrast-Induced Acute Kidney Injury. Open Journal of Nephrology, 14, 185-195. https://doi.org/10.4236/ojneph.2024.142018