Remote Ischemic Preconditioning to Prevent Contrast Nephropathy

Overview

Contrast-medium induced nephropathy (CIN) is a frequent and devastating complication of coronary angiography, occurring in 10-50% of cases. As would be expected, the incidence of CIN is much higher in patients with underlying renal dysfunction. Multiple trials have found CIN to be an independent predictor of prolonged hospitalization and both 30 day and 1 year mortality in patients with coronary artery disease. Intravenous contrast dye is felt to cause renal ischemia as the mechanism of injury. Unfortunately, despite the significant morbidity and mortality with CIN, there are few therapeutic interventions to reduce the risk with the exception of hydration and high dose statin therapy. Recently, remote ischemic preconditioning (RIPC), a process of inducing transient arm ischemia by inflating a blood pressure cuff to 200 mmHg for 3 repetitive 5 minute cycles, leads to a systemic cytoprotective response and ultimately reduces ischemic renal injury, myocardial injury, and even cerebral injury following coronary bypass grafting. While there is significant data supporting the role of RIPC in reducing systemic ischemic injury in surgical patients, there is only one small trial studying RIPC in patient's undergoing coronary angiography. The investigators hypothesize that RIPC will reduce the incidence of contrast-induced nephropathy in patients with baseline renal dysfunction undergoing coronary angiography for stable or unstable coronary artery disease.

Contrast-medium induced nephropathy (CIN) is a frequent and devastating complication of coronary angiography, occurring in 10-50% of cases dependent on individual risk factors (JACC 2004; 44:1393). Multiple trials have found CIN to be an independent predictor of prolonged hospitalization and both 30 day and 1 year mortality in patients with coronary artery disease (Clin Res Cardiol 2009;98:765, JACC 2004:44:1780, Ann Int Med 2009;150:170, JACC 2008; 51: 1419). The largest retrospective study of over 16,000 hospitalized patients exposed to iodinated contrast found an in-hospital mortality rate of 34% in subjects developing CIN versus 7% in matched control subjects (JAMA 1996;275:1489). Despite the incidence of CIN and the deleterious outcomes, few therapies exist to prevent CIN other than hydration and withdraw of nephrotoxic medications prior to coronary angiography. Remote ischemic preconditioning (RIPC) is a protective response resulting from transient episodes of ischemia, followed by reperfusion, to vascular beds remote from the organ which will undergo the prolonged ischemic insult. Studies in humans indicate that RIPC decreases cardiac enzyme release, clinical events, and improves mortality in patients undergoing elective coronary bypass surgery (Circulation 2009;119:820; Lancet 2007;370:575, Lancet 2013; 382: 597). In addition to the cardio-protective effects of RIPC, a small, single center randomized trial showed a reduction in the incidence of contrast-medium induced nephropathy of approximately 30% in patients receiving RIPC prior to elective coronary angiography compared to a control population (Circulation 2012; 126:296). RIPC was safely performed in all of these studies by inflating a blood pressure cuff to supra-systolic levels (200mmHg) for 3 five minute episodes separated by 5 minutes of reperfusion. RIPC is a well-tolerated, easily administered mechanism that may reduce the incidence of contrast-mediated nephropathy. However, additional and larger trials are needed to validate the use of RIPC in both elective and urgent coronary angiography in patients at risk for contrast-medicated nephropathy.