Hemodynamic Depression Tied to Kidney Injury After CAS in Patients With Renal Disease

In patients with preexisting renal disease, the risk of acute kidney injury (AKI) following carotid artery stenting (CAS) may be more common than previously thought, with hemodynamic depression playing a substantial role in the pathophysiology that leads to the injury. The findings were published in the September 1, 2015 issue of JACC: Cardiovascular Interventions.

Researchers led by Carlo Briguori, MD, PhD, of Clinica Mediterranea (Naples, Italy), examined the occurrence of AKI and its impact on events in 126 patients (mean age 76 years; 75.5% men) with CKD who underwent CAS at their institution between February 2009 and September 2013. Of these, 32% had symptomatic carotid artery disease.

Serum creatinine (SCr) was measured the day before the procedure, and at 24 hours, 48 hours, and 1 week after administration of contrast media. AKI was defined as an increase of ≥ 0.3 mg/dL in SCr at 48 hours or the need for dialysis. 

Severity of AKI was defined according to the Acute Kidney Injury Network criteria as: 

• stage 1: SCr increase ≥ 0.3 mg/dL, or ≥ 1.5 to 1.9 × from baseline
• stage 2: SCr increase ≥ 2.0 to 2.9 × from baseline
• stage 3: SCr increase ≥ 3.0 × from baseline or the need for dialysis

Technical success of CAS was 100%. Hemodynamic depression, which occurred in 41% and was persistent in 12%, stemmed from hypotension in the majority of patients (88.5%). Compared with those who did not develop hemodynamic depression, those who did tended to have smaller vessel size and to have lesions involving the bulb. They also less often had previous endarterectomy but more often were treated with nitinol and open-cell stents.

AKI Predicts Short-Term Adverse Events

Overall, AKI occurred in 26 patients (21%), and was classified as stage 1 in most (81%) and stage 2 in the remainder. Compared with patients who did not develop AKI, those who did were more often men, active smokers, anemic, and had higher Mehran risk scores. AKI patients had a higher frequency of balloon predilation, larger mean stent diameter, and more often received nitinol stents.

Baseline characteristics between the AKI and no-AKI groups were similar, including kidney function and contrast volume. Mehran risk score was higher for AKI patients (10 vs 8; P = .032), as was hemodynamic depression (65.5% vs 35%; P = .005). The threshold of hemodynamic depression duration for predicting AKI development was 2.5 minutes (sensitivity 54%, specificity 82%). Vasopressor use was 50% in patients with AKI and 22% in those without (P = .007).

Multivariable analysis confirmed that hemodynamic depression, Mehran risk score, and male sex independently predicted AKI. Development of AKI and hemodynamic depression foretold higher risk of major adverse events at 30 days (table 1).

In-hospital and 30-day major adverse events were noted in 9.5% of patients, occurring more frequently in those with AKI (19.5% vs. 7%; P = .058).The difference in risk was driven by higher mortality in patients with AKI (11.5% vs 2%; P = .026), and major bleeding only occurred in 1 AKI patient (P = .21).

Hemodynamic Depression Plays ‘Independent Role’

According to the study authors, the observed AKI rate of 21% was higher than expected. Additionally, the results reinforce “the independent role of hemodynamic depression in the pathophysiology of AKI in this clinical setting,” they say.

Hemodynamic depression, they note, has been linked to a greater risk of major periprocedural adverse clinical events, including death and stroke. In fact, in the CAS arm of the CREST trial, patients who had stroke were more likely than those who did not to suffer hemodynamic depression requiring treatment, Dr. Briguori and colleagues observe. Intraoperative hemodynamic depression “has the potential to cause an ischemia-reperfusion injury, which, in turn, may substantially contribute to postoperative AKI,” they add.

Longer time at low blood pressure has been shown to increase the risk of 30-day mortality after surgery, the researchers note, adding that the autoregulation pathway may be impaired in patients with CKD. “As such, optimizing perioperative hemodynamics may mitigate or prevent this complication,” they observe.

While some researchers have proposed that CKD may only be a marker for more advanced disease and more comorbidities in CAS patients, the current results indicate that “the unfavorable prognosis following CAS is mostly limited to CKD patients experiencing postprocedural AKI,” Dr. Briguori and colleagues suggest.  

Novel Techniques, Treatments May Reduce Risk

In an editorial accompanying the study, Peter A. McCullough, MD, MPH, Allan Young, DO, and William P. Shutze, MD, of Baylor University Medical Center (Dallas, TX), say the finding of intraprocedural hypotension as a major determinant of AKI during CAS “is novel and suggests transient well-documented decreases in systolic blood pressure (< 90 mm Hg) or bradycardia (< 60 beats/min) have an additive impact on [contrast-induced] AKI in addition to the relatively modest contrast volumes used in this series.”

They propose that measures to reduce bradycardia and hypotension should include:

• Pretreatment with atropine and cessation of antihypertensives and phosphodiesterase inhibitors on the day of the procedure
• Preparation and ready access of IV dopamine 
• Ready availability of isoproterenol for bradycardia that occurs despite anticholinergic premedication
• Gentle volume administration with care not to overhydrate if hypotension occurs

Dr. McCullough and colleagues also say newer vascular interventional techniques or novel vasopressor support may lessen the frequency of bradycardia and hypotension, thereby reducing the risk of contrast-induced AKI in patients with renal disease.

“Additionally, because [contrast-induced] AKI during carotid artery stenting appears to be amplified by hemodynamic instability, it could conceivably be ameliorated by remote ischemic preconditioning using transient arm ischemia with a blood pressure cuff, as recently reported in several trials,” they conclude.

Sources: 
1. Donahue M, Visconti G, Focaccio A, et al. Acute kidney injury in patients with chronic kidney disease undergoing internal carotid artery stent implantation. J Am Coll Cardiol Intv. 2015; 2015;8:1506-1514. 
2. McCullough PA, Young A, Shutze WP. Acute kidney injury after carotid artery stenting [editorial]. J Am Coll Cardiol Intv. 2015;8:1515-1517.

Disclosures:  

• Drs. Briguori and McCullough report no relevant conflicts of interest.

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