Discussion
In cases of stroke, CTA is recommended to assess occlusion severity and guide potential endovascular interventions, such as mechanical thrombectomy. However, the administration of contrast during CTA and then again during subsequent thrombectomy raises legitimate concerns regarding its safety in patients with AIS, specifically the risk of developing CIN. The predicament, therefore, lies in finding the balance between obtaining necessary diagnostic information and mitigating potential complications of the procedure, ensuring safety and the best possible outcome for the patient either way.
Based on our systematic review and meta-analysis of data, we found that there was no significant change in the odds of developing AKI among those receiving CTA/CTP versus the patients who did not receive contrast (p=0.19). These findings challenge CIN concerns in patients with AIS undergoing CTP/CTA, suggesting that such fears may be unfounded. Moreover, waiting for serum creatinine values before initiating intervention unnecessarily delays timely and potentially life-saving measures in a clinical context where every minute counts.
A meta-analysis on the association between CTA/CTP administration in patients with AIS and AKI was conducted in 2017, showing that contrast administration was not linked with the development of AKI in patients with AIS.21 Since then, other studies have been published with small sample sizes, warranting a comprehensive meta-analysis to synthesise the available evidence on this topic and accurately guide clinical practices for the management of AIS. We included two recent studies from recent years, Brito et al and Lim et al, both of which administered similar concentrations of contrast and showed no significant incidence of AKI in the studied population.
Brito et al encompass patients with a history of DM and baseline CKD, even including a patient in the control group requiring haemodialysis.9 The study compared the occurrence of AKI contrast exposed group versus contrast unexposed group using the Kidney Disease Improvement Global Outcome criteria. It showed a 6.2% incidence in the contrast exposed group, compared with 1.0% in the contrast unexposed group. However, correction for continuity was applied and showed no statistical difference between the two groups (p=0.073). Overall, the study concluded that contrast is not an independent variable for the occurrence of AKI in patients with AIS.
Lim et al evaluated the long-term renal outcome in patients with AIS. In contrast to most of the included studies, which evaluated the renal outcome within 48–72 hours of contrast administration, this study monitored the serum creatinine levels after 5 days post-contrast to up to >30 days post-contrast.8 A prolonged monitoring period provides insights into the occurrence of AKI over the long term. Although the initial rate of AKI was 7.6% of the population (95% CI 4.2 to 11.0), most cases showed no new or persistent AKI cases, and that serum creatinine levels returned to normal within 14 days. Their findings further support the absence of any AKI cases solely attributable to CIN and shed light on various renal confounders contributing to AKI events. To further evaluate this, future studies could focus on using MicroRNAs as a specific biomarker for predicting the prognosis of CIN, building on the findings of the study conducted by Toruan et al.22
The initial analysis of single-arm studies yielded a high heterogeneity (87.97%) which was subsequently addressed by a sensitivity analysis that involved the removal of two studies, Josephson et al19 and Lim et al.8 A reduction in heterogeneity to zero was observed. Josephson and colleagues assessed patients who received a specific stroke CT protocol whereas Lim and colleagues reported on long-term renal outcomes after the CT procedures. It is possible that variation in the study approach introduced heterogeneity into the meta-analysis.
The added evidence supporting the absence of an increased likelihood of AKI after contrast exposure holds significant importance within the selected population of patients with AIS. This is because impaired kidney function is known to be associated with worse outcomes in stroke.23–25 Therefore, the evidence proving the lack of association between contrast exposure and AKI carries dual implications. First, it provides valuable guidance for clinical practices, ensuring physicians can make informed decisions. Second, it helps mitigate the impact of comorbid factors that are known to be linked with increased mortality in AIS. These promising findings relieve physicians from concerns about CTA/CTP posing a risk of poorer outcomes in AIS. Consequently, it becomes clear that CTA/CTP is a safe and uncomplicated choice, eliminating the need for excessive deliberation.
This meta-analysis has a few limitations. First, all studies included are retrospective, not prospective, with no randomised controlled trials being conducted. As a result of the observational nature, all the studies will be affected by a selection bias, as patients with significantly known elevated creatinine levels would generally avoid contrast exposure as a precaution. As no recommendation can be made that could knowingly increase mortality, as is the case here, this bias is unlikely to be eliminated in practicality. However, when comparing patients with CKD to those without, there was still no link between increased baseline creatinine and AKI in the selected population group. There is also heterogeneity in the type and dose of contrast medium used among the studies. There is also variation in the definition of AKI across studies. However, the critical point is that most studies defined it as an increase in creatinine value of 25% from baseline. As there is no established specific test or biomarker to eliminate alternative causes of AKI from CIN, it is difficult to reliably separate when exactly AKI is caused by contrast compared with other risk factors.26
