Contrast-associated acute kidney injury following intravenous contrast media computed tomography; new concept and future directions: A systematic review study on emergencies patients

Implication for health policy/practice/research/medical education: In this systematic review of studies that investigated the incidence of acute kidney injury following intravenous contrast media for computed tomography in emergency patients


Introduction
Computed tomography (CT) due to its high sensitivity and specificity is a practical method in the diagnosis of various disorders (1).There are several benefits to using CT imaging, including its quick availability, lower expenses, shorter scan durations, non-invasively, and improved patient comfort and tolerability (2).To increase the CT image quality, contrast-enhanced computed tomography (CECT) form is developed, which is crucial for diagnosing and treating many urgent medical conditions often seen in emergencies (3).Annually, more than 80 million doses of iodinated contrast media are given globally for performing CT scans, making it one of the most frequently prescribed agents in all fields of medicine (4).One drawback of utilizing a CECT-based imaging system is the potential safety risks associated with the iodinated contrast agents utilized for imaging purposes (2).Renal failure is a common outcome caused by intravenous contrast media administration (ICMA) and is known as contrast-induced nephropathy (CIN) (5).Post-contrast acute kidney injury (AKI), historically known as CIN ( 6) is a common form of renal failure that occurs within 48 to 72 hours after ICMA (7).Despite their clinically valuable and widespread use of CECT, deciding whether to administer contrast media can be complicated due to concerns about causing AKI (4).Although with intravenous contrast agent administration image quality can be improved, the risk of AKI is a main consideration (6).This study investigates the incidence risk of contrast-associated AKI following ICMA for CT scans.

Objectives
This study aimed to evaluate the correlation between AKI incidence and ICMA for CT scans in emergency patients.

Study design
This systematic review aimed to evaluate the incidence of AKI following ICMA for CT scans in emergency patients.The study protocol was conducted based on PRISMA (Preferred reporting items for systematic reviews and meta-analyses) checklist (8), and registered on the PROSPERO (CRD42023448461) and Research Registry (UIN: reviewregistry1690) website.

Search strategy
Search strategies were conducted using keywords across international databases such as Web of Science, PubMed, Scopus, Embase, and Cochrane, with no place and time limitation.Dimension, DOAJ, OpenGrey, WorldCat, and Google Scholar search engines were searched for a complete search.Additionally, manual searching was conducted using the references of related articles.The search strategy was upgraded until March 2023, using keywords, including acute kidney injury, acute renal insufficiencies, acute renal injury, acute kidney failures, acute renal failures, contrast media, intravenous computed tomography contrast media, radiocontrast agents, contrast agent, radiopaque media, contrastassociated nephropathy, contrast-induced nephropathy, emergencies, and emergency treatment.
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Inclusion criteria
Original studies that investigate the correlation between AKI incidence and intravenous contrast media CT in emergency patients.

Exclusion criteria
Exclusion criteria included studies with missing required data, no full-text available studies, low quality, and duplicates.Conference studies, case reports, systematic reviews, meta-analyses, and letter-to-editors' studies also were excluded.Additionally, studies that investigated contrast-associated nephropathy incidence in nonemergence and pediatric patients were excluded.

Quality assessment
For quality assessment, two reviewers separately assessed the articles based on the STROBE (strengthening the reporting of observational studies in epidemiology) checklist for the observational studies.This checklist includes 22 items; each item is worth 2 points, and these points are added together to give a total score.Values 1-15 mean low quality, 16-30 medium, and more than 30 high quality.We set the cutoff point at 15 (9).Any disagreement was resolved by a third reviewer re-evaluating the article and reaching an agreement on a single option.All included studies were of good quality.

Data extraction
To prevent the risk of data collection bias, two researchers who were not the study searchers, separately derived the data using a checklist, including the first author's name, publication date, place, study design, mean age, sample size, population, AKI definition and incidence, study objective and final results.In case of disagreement, data were re-investigated by a third inspector.

Results
In this review study, studies investigating the correlation between AKI incidence and intravenous CT contrast media in emergency patients were assessed based on the PRISMA guideline.The initial search identified 1185 studies.After duplication, 652 were excluded.Following the abstract review, 417 of 533 remaining studies were removed due to meeting no inclusion criteria, and 116 studies were assessed for retrieval.After assessment for retrieval, 49 studies were excluded, and 67 were evaluated for eligibility.Eventually, 28 studies were included in the final review and 39 were excluded based on exclusion criteria (Figure 1).Results showed that 28 studies from 10 countries were included in this systematic review.The total sample size was 48878 patients.The biggest study in terms of sample size was conducted by Su et al (10) in Taiwan with 10143 patients, and the smallest was conducted by Tremblay et al (11) in Canada with 56 patients.When it comes to study design, the majority of conducted studies were retrospective cohorts.The biggest AKI incidence rate was reported in the study by Lin et al at 15.9% (12), and the smallest incidence rate was reported by McGillicuddy et al at 1.9% (13).The most common definition for AKI in most of the studies was creatinine (Cr) increase >0.5 mg/dL or > 25% compared to baseline within the initial 48 to 72 hours after exposure to intravenous contrast media.Many studies have found no significant association between the AKI incidence and ICMA for CT scan (Table 1).

Discussion
In a review of 28 studies with a sample size of 48878 people, result demonstrated that the AKI incidence after ICMA for CT scans was reported at the range of 1.9% to 15.9% in different studies.Most studies reported no association between the AKI incidence and ICMA for CT scans, and this dose of contrast media could not cause AKI in septic patients, two studies by Hinson et al ( 4) and Hsu et al (30) showed that using CECT is not associated with the incidence of AKI.In stroke patients, five studies evaluated the correlation between CECT and AKI incidence, and all    (13) reported that ICM in trauma patients cannot increase the risk of AKI; however, Bashir et al (28) stated that CIN is a serious risk following CECT.A study by Mitchell et al (5) also stated that CECT is associated with CIN incidence and renal failure.Some studies on initial diagnostic CT in ED patients demonstrated no significant correlation between the incidence of AKI and ICMA for CT scans (4,17,19,29).The other studies on burn patients (18), gastrointestinal surgery (15), blunt splenic injury (16), pulmonary embolism (25), and survivors of cardiac arrest patients (26) reported that ICMA does not increase the risk of AKI after CT scans in emergency patients.
On the other hand, some studies reported that specific situations can increase the risk of AKI incidence after the ICMA for CT scans; Su et al stated that ICMA in the presence of eGFR less than 30mL/min increases the risk of AKI incidence (10).Huang et al reported that the correlation between AKI occurrence and IV contrast cannot be significant unless in the presence of risk factors such as hypotension, diabetes, and pre-contrast Cr >1.5 mg/ dL (22).In a study by Dagar et al, older age, hypotension, anemia, and hypoalbuminemia were reported as the most common risk factors for the incidence of AKI following contrast media administration (23).Hyperglycemia (12), diastolic dysfunction (24), transient hypotension (27), pre-existing CKD factors (31), and diabetes mellitus (32) were the other reported risk factors for AKI incidence after contrast media administration in reviewed studies.

Conclusion
The review of the literature showed that intravenous contrast media with a dose of CT scans doesn't cause AKI except in the presence of a specific situation such as older age, diabetes mellitus, anemia, hypoalbuminemia, hypotension, eGFR < 30 mL/min, and pre-contrast Cr >1.5 mg/dL.The results of our study can be a valuable resource for doctors who may be worried about the impact of CECT on kidney function.

Table 1 .
Baseline information of included studies in the systematic review