Effectiveness of Remote Ischemic Preconditioning for Prevention of Contrast Induced Acute Kidney Injury in Patients Undergoing Coronary Angiograms.

Description

The use of imaging is increasing in clinical practice, either for diagnosis or intervention. In these imaging processes, contrast medium (CM) is widely used. However, CM administration can induce contrast-induced nephropathy (CI-AKI). CI-AKI is the third most common cause of renal insufficiency, and its incidence varies from 2% to 50% depending on patient risk factors; in addition, studies have shown that CI-AKI occurs in 2% to 25% of patients undergoing coronary intervention. CI-AKI is associated with significant mortality and morbidity in patients undergoing coronary angiography or other diagnostic contrast studies. We assessed the latest promising evidence on the ability of remote ischemic preconditioning (RIPC) to reduce the incidence of CI-AKI in patients undergoing Coronary Angiogram (CA) or diagnostic contrast studies such as CT angiogram, while at the same time being a non-invasive, low cost, easy, and safe method with absence of adverse effects. However, more randomized controlled trials are needed to confirm these preliminary results.

The aim of this study is to minimize the incidence of CI-AKI at the University of Texas Medical Branch (UTMB). If found to be an effective method, RIPC would help minimize the incidence of CI-AKI in all institutions across the globe, who would adopt this intervention.

The primary objective: i) reduce the rise in creatinine to 75, hypotension, CHF, anemia, diabetes, patients with a baseline serum creatinine greater than 1.5 mg /dL and the volume of contrast media used. The presence of underlying renal dysfunction appears to provide particular susceptibility. Although most studies exclude patients with severe renal dysfunction, Rihal et al. report that in patients with a creatinine >3.0 (and GFR < 30) the incidence of CI-AKI was 31%.

Unfortunately, robust strategies to prevent CI-AKI are minimal. Research has examined the use of sodium bicarbonate, adding N-acetylcysteine or holding RAAS (Renin-angiotensin-aldosterone system) blockers but found all these three strategies ineffective. At this time the only validated strategy to prevent CI-AKI is the use of fluid administration to ensure adequate renal perfusion. Pre- and post-procedure intravenous fluid administration is currently considered standard of care. In one study involving 408 patients with intact renal function receiving isotonic saline (NS) (1cc/kg/h before percutaneous angiography and 24 hours after) the incidence of CI-AKI within the following 3 days was 21% in the group without NS and 11% in the NS+ group (p=0.016). Further, CI-AKI was associated with increased risk of death (15.2% vs 2.8%; p<0.0001) and need for renal replacement therapy (13.4% vs 0%; p<0.0001). In another trial involving 216 patients, pre- and post-procedure hydration reduced the incidence of CI-AKI in the hydrated group versus the non-hydrated control group 20.4% versus 35.2%, p25% compared with the baseline value within a period of 48-72 hours after contrast media (CM) administration.

The definition of Remote Ischemic Preconditioning is not as simple. According to a pathophysiologic concept, repeated short duration ischemia in an organ induces a ”resistance” to a later prolonged ischemia. That is, a brief period of ischemia induces endogenous protective mechanisms that increase tissue tolerance to subsequent lethal ischemia. This is a physiological adaptive mechanism of protection of tissues faced to hypoperfusion, which has therapeutic potential when ischemia-reperfusion is induced in a targeted way. In 1982, this mechanism called ischemic preconditioning (IPC) was highlighted for the first time on canine models in myocardial infarction. In experiments, cycles of alternating ischemia and reperfusion were applied to dogs by using a balloon to occlude a coronary artery. This allowed the prevention of necrotic myocardial territories. These results have opened prospects on a possible use of this method of preconditioning for myocardial protection as well as preconditioning for renal protection in humans.

Our remote ischemic preconditioning protocol would comprise four (4) cycles of 5 min of ischemia followed by 5 min of reperfusion for the experimental group. The BP cuff would be placed around the upper non-dominant arm (e.g upper left arm in a right-handed patient) and inflated to a pressure set at 50 mmHg higher than baseline systolic BP to induce transient ischemia followed by subsequent deflation to ensure 5 minutes of reperfusion in the RIPC group. The absence of distal pulse would be confirmed with Doppler evaluation or palpation of the radial and ulnar artery.

In the control group, sham preconditioning would be performed by inflating an upper-arm blood pressure cuff to diastolic pressure levels and then deflating the cuff to 10 mm Hg below diastolic pressure for 5 minutes to maintain nonischemic upper-arm compression for blinding purposes with regard to the patients; this will be followed by complete deflation of cuff for 5 minutes. Again a total of four cycles would be ensured. In individuals presenting with BMI > 30 kg/m2 , a dedicated blood pressure cuff for obese patients will be used. Time from RIPC to the procedure (either CA or diagnostic contrast study) will be within 30 kg/m2 , a dedicated blood pressure cuff for obese patients will be used. Time from RIPC to the procedure (either CA or diagnostic contrast study) will be within <120 min in all studies.

In addition to our above mentioned intervention (RIPC), all patients will receive standard of care for patients with impaired renal function undergoing CA as mentioned below (No.1 and No.2) :-

No.1: Recommended hydration will consist of saline 0.9% solution infusion at a rate of 1 mL/Kg/h for 12 hours prior to contrast medium injection and up to 12 hours thereafter, unless there is evidence of fluid overload thus contraindicating further fluid administration.

No.2: Metformin, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, diuretics, and non-steroidal anti-inflammatory drugs will be discontinued at least 24hours before the angiography.