Ischemic Preconditioning for Prevention of Contrast Medium–Induced Nephropathy

Abstract

Background-Contrast medium-induced acute kidney injury is associated with substantial morbidity and mortality. The underlying mechanism has been attributed in part to ischemic kidney injury. The aim of this randomized, double-blind, sham-controlled trial was to assess the impact of remote ischemic preconditioning on contrast medium-induced acute kidney injury. Methods and Results-Patients with impaired renal function (serum creatinine Ͼ1.4 mg/dL or estimated glomerular filtration rate Ͻ60 mL ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 ) undergoing elective coronary angiography were randomized in a 1:1 ratio to standard care with (nϭ50) or without ischemic preconditioning (nϭ50; intermittent arm ischemia through 4 cycles of 5-minute inflation and 5-minute deflation of a blood pressure cuff). Overall, both study groups were at high risk of developing contrast medium-induced acute kidney injury according to the Mehran risk score. The primary end point was the incidence of contrast medium-induced kidney injury, defined as an increase in serum creatinine Ն25% or Ն0.5 mg/dL above baseline at 48 hours after contrast medium exposure. Contrast medium-induced acute kidney injury occurred in 26 patients (26%), 20 (40%) in the control group and 6 (12%) in the remote ischemic preconditioning group (odds ratio, 0.21; 95% confidence interval, 0.07-0.57; Pϭ0.002). No major adverse events were related to remote ischemic preconditioning. Conclusions-Remote ischemic preconditioning before contrast medium use prevents contrast medium-induced acute kidney injury in high-risk patients. Our findings merit a larger trial to establish the effect of remote ischemic preconditioning on clinical outcomes. Clinical Trial Registration-URL: http://www.germanctr.de. Unique identifier: U1111-1118-8098. (Circulation. 2012;126:296-303.)

Remote Ischemic Preconditioning and Renoprotection

“…2 rIPC has primarily been applied to the myocardium as a target organ, but subsequent studies showed that brief ischemia induced in nontarget tissue, most commonly in the limb or arm, confers protection at a remote site such as the brain, lung, kidney, intestine, or skeletal muscle. [3][4][5] rIPC causes a similar degree of tissue protection, as does IPC. 6 Kidneys are one of the major organs of interest for clinical application of rIPC.…”

“…In this regard, we and others recently demonstrated that rIPC may offer a novel noninvasive and virtually cost-free treatment strategy to decrease acute renal impairment incidence in patients undergoing cardiac catheterization. 5,9 This article evaluates the current evidence for rIPC as a potential renoprotective strategy and discusses its possible clinical applications.…”

“…Indeed, our group recently addressed the effects of rIPC in a high-risk patient populations in the RenPro trial. 5 This study included 100 adults (mean age 73.2 years) with impaired renal function (serum creatinine.124 mmol/L and/or eGFR,60 ml/min per 1.73 m 2 ; mean Mehran score 13) who underwent elective coronary angiography. Enrolled patients were randomly assigned to either control group (N550) or to rIPC before cardiac intervention (N550).…”

Atherosclerotic renal artery stenosis is associated with elevated cell cycle arrest markers related to reduced renal blood flow and postcontrast hypoxia

“…Remote ischemic preconditioning induces the release of IGFBP-7 and TIMP-2 that predicts the protective effect of this intervention from subsequent kidney injury induced by cardiac surgery. Patients with higher levels of IGFBP7 and TIMP-2 before cardiac surgery had a reduced rate of AKI compared with patients with lower IGFBP7 and TIMP-2 concentrations [11,33]. Our results demonstrate that renal vein levels for these markers of G1 cell cycle arrest in the kidney are elevated in patients with chronic renal ischemia and that higher levels were associated with reduced acute changes in tissue hypoxia after contrast imaging and stenting.…”

“…Repetitive periods of myocardial ischemia cause no harm to cardiac tissue [32]. More recently, 'remote' ischemic preconditioning using repetitive, transient tourniquet occlusion to arm blood flow has been shown to prevent contrast-induced AKI in high-risk patients and reduces the development of AKI after cardiac surgery [33,34]. Importantly, remote ischemic preconditioning was most effective in patients that developed increased levels of IGFBP-7 and TIMP-2 during the conditioning procedure in that study [11].…”