Catheterization and Cardiovascular Interventions 73:725–730 (2009)
Complete Versus Partial Distal Embolic Protection During Renal Artery Stenting Khalil Kanjwal,1 MD, Steven Haller,1 MA, Michael Steffes,2 MD, Renu Virmani,3 MD, Joseph I. Shapiro,1 MD, Mark W. Burket,1 MD, Christopher J. Cooper,1 MD, and William R. Colyer Jr.,1* MD Objective: The aim of this study was to evaluate whether complete embolic protection is superior to partial embolic protection for preservation of kidney function during renal artery angioplasty and stenting. Background: Renal artery angioplasty and stenting (RAAS) is a common treatment for atherosclerotic renal artery stenosis. However, RAAS may be complicated by peri-procedural loss of kidney function. Methods: In total, 44 patients were randomized to embolic protection devices (EPD) use; 25 complete and 19 partial embolic protection. These patients were further randomized to receive abciximab (n 5 23) or placebo (n 5 20). MDRD glomerular filtration rate (GFR), was used as the primary measure of renal function. Creatinine was measured by a modified Jaffe reaction using the IDMS-traceable assay. The primary endpoint was the percent change in estimated glomerular filtration rate (eGFR) 1 month following stent placement. Results: There was no difference in percent change eGFR at 1 month between complete or partial protection (24 6 25 vs. 13 6 30, P 5 0.45). Abciximab was associated with a net improvement in eGFR when compared with placebo (10.5 6 27 vs. 211 6 20, P 5 0.04). On subgroup analysis, the use of abciximab was associated with significantly improved eGFR in the partial distal embolic protection group (114 6 33 vs. 217 6 13 %, P 5 0.018) but not in the complete distal embolic protection group (12.5 6 26 vs. 211 6 24, P 5 0.42), however, there was no interaction between completeness of protection and abciximab on eGFR (P 5 ns). Capture of embolic material was more likely with complete protection when compared with those receiving partial protection (51% vs. 21%, P < 0.05). Conclusion: Complete protection was superior to partial protection for the capture of athermanous debris during renal artery stenting. However, this was not associated with improved renal function. Importantly, Abciximab conferred a benefit for renal function that was independent of the degree of embolic protection. ' 2009 Wiley-Liss, Inc. Key words: kidney; peripheral vascular disease; platelets; stenosis; stents
INTRODUCTION
Atherosclerotic renovascular disease is an important public health problem affecting up to 5% of 60 million hypertensive patients in the United States [1]. In
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patients with renal insufficiency, the incidence of unsuspected renal artery stenosis (RAS) is as high as 24% [2]. RAS greater than 60% has been reported in 6.8% of patients older than 65 years of age [3] and is associated with increases in cardiovascular, cerebrovas-
University of Toledo, Toledo, Ohio University of Minnesota, Minneapolis, Minnesota 3 CVPath Institute, Gaithersburg, Mary Land
AVE, Abbott Vascular, WL Gore, Volcano Therapeutics Inc., Prescient Medical, CardioMind Inc., Direct Flow, and Atrium Medical Corp.
Conflict of interest: Dr. Cooper has received research grant from the RESIST and CORAL studies. Dr. Colyer has received research support from Astra-Zaneca, Sanofi-Aventis and served on the speakers’ bureau for Boehringer-Ingleheim, Pfizer, and Radi. Dr. Virmani has received research support from Medtronic AVE, Atrium Medical Corp, CardioKinetix, Osiris Therapeutics Inc., Edwards Life Sciences, Nitinol Device and Componenets, Hancock Jaffee Labx Inc., Biotegra, CVRx Inc. Dr. Virmani has also served as a consultant to or on the advisory board for Medtronic
*Correspondence to: William R. Colyer, Jr., MD, Assistant Professor of Medicine, Cardiovascular Division, University of Toledo, 3000 Arlington Ave., MS 1118, Toledo, OH 43614. E-mail:
[email protected]
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' 2009 Wiley-Liss, Inc.
Received 17 November 2008; Revision accepted 29 November 2008 DOI 10.1002/ccd.21932 Published online 5 February 2009 in Wiley InterScience (www. interscience.wiley.com).
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cular, and all cause mortality [4]. The treatment options for RAS include medical management, angioplasty with and without stenting and surgical revascularization. Although angioplasty and stenting has become the preferred method of revascularization for RAS [5–8], the effects of renal angioplasty and stenting on renal function remain controversial. Many studies have demonstrated worsening of renal function following renal angioplasty and stenting [5– 9]. Several etiologies have been proposed for postprocedure renal function deterioration including contrastinduced nephrotoxicity, progression of concomitant nephrosclerosis, hyper-perfusion injury, glomerular injury, and distal atheroembolization [6,10–13]. Distal embolization has been increasingly recognized as a cause of worsening outcomes following intervention in native coronary arteries and saphenous vein grafts [14,15], carotid arteries [16–21], as well as the renal arteries [7,10,13,22]. To circumvent the problem of distal embolization a concept of protected intervention with the use of embolic protection devices (EPD) has been developed. EPD use during saphenous vein graft stenting and carotid stenting has been shown to improve outcome [19–21,23–25]. Some studies have suggested beneficial effects of protection devices on postprocedural renal function following renal stenting [7,8,10]. The mechanism of benefit is thought to be a capture of atheroembolic debris. Importantly, postprocedure renal function is a significant predictor of mortality in these patients. However, depending on the bifurcation pattern of the renal artery, complete protection of the kidney may not be possible if there is an early branch that originates before the site of EPD deployment. The aim of the current study was to determine whether partial distal embolic protection was equivalent to complete distal embolic protection for preservation of renal function. MATERIALS AND METHODS
The current study evaluated patients who were randomized to EPD use in the RESIST trial [26]. The methods of the RESIST trial have been described previously [26]. Briefly, the study (NCT00234585) was conducted by the Clinical Coordinating Center at the University of Toledo with funding provided by the sponsors, with study conduct, analysis, and reporting performed independent of the sponsors. ICH good clinical practice guidelines were followed with patients providing informed consent in an IRB-approved protocol with 100 patients recruited from seven sites. Inclusion required a history of hypertension, renal insufficiency, heart failure, or angina with poorly controlled hypertension and the presence of one or more renal ar-
tery stenoses, 50%, and
