The Risk of Acute Radiocontrast-Mediated Kidney Injury Following Endovascular Therapy for Acute Ischemic Stroke Is Low

Discussion

In this small study, the risk of RCM-AKI in the patient with AIS undergoing endovascular therapy was very low (3%) with minimal significant long-term clinical consequences. Although the incidence reported in the literature concerning endovascular interventions for ACS ranges from 10% to 20%,^15–17 our small study size makes it impossible to make a fair intercohort comparison. A much larger study is required to determine the true incidence of RCM-AKI in endovascularly treated patients with AIS before such comparison can be made.

In the coronary angiography population, known associations with RCM-AKI include the use of ionic RCM, higher baseline serum creatinine levels, male sex, a history of diabetes mellitus, volume of contrast agent, and chronic renal insufficiency.^18,19 In other studies of patients receiving RCM during coronary angiography, associations with RCM-AKI include increased age, preprocedural hypovolemia, congestive heart failure, cirrhosis, proteinuria, IA RCM administration, prior NSAID use, and hypertension.¹²

The development of RCM-AKI is associated with prolonged hospitalization, adverse cardiac events, and increased mortality. However, this may be an epiphenomenon of the severity of underlying cardiac and comorbid systemic conditions. Patients with RCM-AKI who require hemodialysis have a high in-hospital mortality.¹²

The data from this cohort are descriptive in nature but can serve as a useful means to compare RCM-AKI in patients with AIS and ACS undergoing intervention. The RCM-AKI incidence observed in the present study compares favorably with the 10%–20% in the ACS population. The RCM-AKI incidences in the 3 most recent coronary intervention studies are all higher than that observed in our cohort: 11.5% (45/392, P = .008) reported by Wickenbrock et al,¹⁵ 10.2% (41/400, P < .03) reported by Jabara et al,¹⁶ and 20.5% (115/561, P < .0001) reported by Marenzi et al.¹⁷ In pooling the 201 separate instances identified in the total of 1353 coronary interventions, the finding of the present study of 3 cases in 99 instances is markedly lower (P < .001).

One key difference in the populations undergoing intervention for ACS versus AIS, however, may be the higher distribution of atherosclerosis and underlying chronic renal insufficiency in the former group. The overall incidence of renal insufficiency on admission (defined as baseline serum creatinine level, ≥1.5 mg/dL) was 5% (5/99) in our cohort, which compares favorably with the 30.5% rate (171/561, P < .0001) in the report by Marenzi et al.¹⁷

Differences in the distribution of renal insufficiency alone may not account for the higher rate of RCM-AKI in patients with ACS undergoing intervention. In a subset of patients with normal baseline creatinine levels, >8% of patients undergoing coronary intervention experienced RCM-AKI.^18,20

Renal insufficiency on admission, however, is likely due to a different etiology in patients with AIS compared with those with ACS. Patients with AIS may present more frequently in a prerenal hemoconcentrated state with acute glomerular insufficiency.²¹ In patients with such prerenal azotemia, glomerular filtration can be normalized with hydration, unlike patients with azotemia from intrinsic renal disease such as those with ACS. None of the 5 patients in our cohort with elevated preintervention creatinine levels developed RCM-AKI, while in fact, all had decreased serum creatinine levels at 48 hours. Furthermore, half (50/99) of all patients in our cohort similarly had a decrease in the serum creatinine level at 48 hours, indicating that patients with AIS may present with dehydration or even that dehydration may predispose certain patients to AIS. Forty-eight-hour reductions in serum creatinine levels may be due to the aggressive rehydration that all patients with AIS receive. In addition, our center is a tertiary stroke care facility, and most of the patients treated endovascularly were transferred from outside institutions. Because the average time to intervention was >6 hours, this may imply a period of de facto preprocedural hydration in those patients undergoing transfer.

One of several other differences between patients with ACS and AIS is the higher incidence of cardiogenic shock in the former group. This complication was a rare observation in our cohort but occurred in 12% of the ACS population studied by Marenzi et al.¹⁷ Second, distal aortic embolization and subsequent renal arteriolar occlusion are a risk of intervention for ACS and less so for AIS. Cholesterol embolization can cause AKI immediately following coronary intervention and is difficult to distinguish from true cases of RCM-AKI.¹² Inclusion of such cases would overestimate the true rate of RCM-AKI following coronary intervention. Finally, the procedural contrast requirement for coronary intervention may be routinely higher than that for endovascular AIS therapy. In fact, this held true because the contrast in the study by Marenzi et al¹⁷ was 265 ± 130 mL, significantly higher than the 189 ± 71 mL administered in our cohort (P < .0001).

In our cohort, any relationship between RCM-AKI and renoprotective-agent administration was indeterminate. Although statin use has been documented to be renoprotective against RCM-AKI,²² we demonstrated a trend toward a higher incidence of statin use in the RCM-AKI group (66% [2/3] versus 20% [19/95], P = .1). Although the evidence for N-acetylcysteine as a renoprotective agent is debated,^23–25 it was neither a variable prospectively tracked in our data base nor is it routinely used before emergent intervention at our institution.

Our study was notably limited by the fact that only 3 patients had RCM-AKI, only 1 of whom was oliguric. Thus, no meaningful analysis could be made in regard to independent risk factors through multivariate analysis. In the RCM-AKI subset, we noted a trend towards diabetes and chronic renal insufficiency, consistent with prior reports. However, for meaningful numbers able to power a multivariate analysis, calculating from the strongest association, diabetes, and assuming a 50% incidence of diabetes within the RCM-AKI subset, one would need a total of 18 patients with RCM-AKI. At a 3% incidence rate, this would require 500 more patients with AIS to undergo endovascular therapy, nearly the pooled sample size of the entire multicenter PROACT, PROACT II, MERCI, and Multi MERCI cohorts.^1,2,4,26 Pooling these previous endovascular studies for analysis may be worthwhile in an endeavor to compare independent risk factors by using multivariate analysis.

Another variable beyond our control was the extent of intravenous hydration before angiography. RCM-AKI prevention is widely debated, and particularly in emergent situations such as AIS, little evidence exists to support any beneficial preventative therapies or techniques other than adequate rehydration and the judicious use of low-osmolality contrast agents.²⁵ Despite the fact that all patients had a period of intravenous rehydration before catheterization, there was no way to assess the rate or total volume of fluid resuscitation.

Our small study size and low overall RCM-AKI rate combined make meaningful comparisons difficult. As an example, the 3 patients with RCM-AKI have a wide range of administered contrast volume (313 ± 241 mL), and this wide deviation precludes detection of any statistical difference from the mean of 185 mL in the patients who did not have RCM-AKI, though the mean is nearly 1.5 times greater. We are not suggesting that our data imply that a larger study would necessarily demonstrate a similar lack of difference, but we are suggesting that one is needed to confirm that the RCM-AKI incidence following endovascular therapy for AIS is truly as low as that demonstrated in our cohort.

Our observational data can also only be descriptive of the true incidence of hemodialysis-requiring RCM-AKI in endovascularly treated patients with AIS. No patient with RCM-AKI in our cohort required hemodialysis, compared with 12/561 (2%) of the patients studies by Marenzi et al.¹⁷ Because such severe RCM-AKI is associated with higher rates of in-hospital mortality,¹² the absence of this requirement in our study population suggests that the true incidence may in fact also be very low, a relevant fact when assessing the overall risk to the patient.

Despite the inability to establish a relationship between RCM-AKI and functional outcome in this study, it is still noteworthy to analyze overall outcome data to compare risk and benefit. In this small sample, 34% (33/97) had a good or excellent outcome (mRS ≤2). Given the 3% risk of RCM-AKI, 30 eligible patients with AIS would need to be treated endovascularly to achieve 10 good outcomes at the risk of 1 case of RCM-AKI. At this point in the early stages of endovascular therapy as a therapeutic option for AIS, we must rely on such descriptive observational data alone to make decisions regarding the overall benefit-to-risk ratio.