Percutaneous intervention for renal artery stenosis was born in controversy and remains a debatable treatment strategy for the 2–4 million Americans affected. However, this important intervention remains the best option for many. This article presents a summary of early examinations and may serve to place the current deliberations into context.
The first peripheral balloon intervention was performed on July 12, 1977, and the first renal artery intervention was performed by Dr. Mahler in the late 1970s.1 Dr. Gruentzig hoped to be the first to perform renal angioplasty but, instead, became the first to publish information about the technique.2 Since that time, renal artery interventions have grown in number to represent an important cost to American medicine, with billings to Medicare increasing by 242% from 1996 to 2001. During the same time frame, renal artery stenting increased 364% and renal artery bypass procedures decreased by 45%.
Contributing factors and prognosis. Renal artery stenosis affects 1–5% of patients with hypertension. The prevalence of significant renal artery stenosis (> 50%) increases with:
3. Coronary disease
4. Abdominal aortic aneurysm
5. Aortic disease
6. Infrapopliteal occlusive disease
7. Renal insufficiency
Some suggest that renal artery stenosis will progress in those with stenosis > 50% and will produce renal artery occlusion in a small percentage of patients (approximately 3%). When one looks at survival probability between renal artery stenosis and no renal artery stenosis, there is a significant reduction of survival at 4 years if stenosis is present. The literature suggests that patients with chronic obstructive pulmonary disease and congestive heart failure in addition to renal artery stenosis have dismal long-term prognoses. A recent single-center study indicated baseline azotemia as the strongest independent predictor of all-cause mortality, with 70% of patients with a creatinine level > 2.5 succumbing within 5 years.3
Several investigators have questioned the value of renal artery angioplasty compared with medical therapy. In fact, as the 30- year anniversary of angioplasty approaches, a number of trials have questioned the value of renal artery intervention.4,5 However, each of the listed concerns resulted from investigations with methodological flaws including limited statistical power, and none of the questionable investigations included use of bailout stenting. Therefore, it could be said that the reported trials really did not reflect the real world. Despite acknowledgement of the reported studies’ weaknesses, some primary care physicians and nephrologists promote a multipronged, aggressive medical management that includes diabetes control, antiplatelet therapy, treatment of hypercholesterolemia, effective antismoking intervention and treatment of chronic renal disease as obviating the need for percutaneous interventions. Indeed, at this stage, renal intervention does not fulfill the American College of Cardiology/American Heart Association criteria for Class I indications described as evidence for and/or general agreement that a given procedure or treatment is beneficial, useful and effective.
PTA trials. A recent Cochrane Database review indicated that only 3 randomized, controlled trials dealing with renal artery revascularization have been reported since 1990.6,7 Of the trials reviewed, the intervention demonstrating most consistent improvement was balloon angioplasty. Lederman and colleagues described experience with renal artery stenting at a single site, reporting few complications or injuries and considerable success. More recent results from the ASPIRE II trial (2005) reported results of a nonrandomized enrollment of 208 patients with either de novo or restenotic renal arteries who received a stent after unsuccessful percutaneous transluminal renal angioplasty. Inclusion criteria for the ASPIRE II trial included failed angioplasty as determined by ≥ 50% residual stenosis, ≥ 10 mmHg mean gradient, ≥ 20 mmHg peak gradient, baseline creatinine £ 3.0 mg/dl and ≥ 2 hypertension medications. Patients with total occlusions and/or nonatherosclerotic obstructions were excluded. Twenty-three sites participated in this trial, which had a primary endpoint of stenosis at 9 months for failed angioplasty compatible with objective performance criteria 3 40% stenosis (percentage). Primary endpoint results are listed in Table 1, with major adverse events shown in Table 2.
Data from the ASPIRE II trial indicate that the reported restenosis rate of 17% was comparable to other reports in the literature. In addition, improvements in blood pressure/ hypertension medication response showed 45% of patients were cured or improved at both 9- and 24-month intervals, with stable serum creatinine levels seen at 24 months postprocedure.
Another investigation examined the impact of a drugeluting stent (DES) on revascularization.10 This study, called the GREAT trial, compared sirolimus-eluting stents (SES) to bare-metal stents (BMS) in atherosclerotic renal artery stenosis. Data from 11 centers showed that usage of SES decreased the numbers of revascularization for patients with > 50% stenosis from 7.7% to 3.8%, suggesting that DES may have some benefit outside coronary intervention. However, more recent data from these same investigators indicate that renal function worsened in all patients (4.6% of the BMS patients and 6.9% in the SES group), with overall major adverse event rates of 23.7% (BMS group) and 26.8% (SES group) at 2 years. These data suggest that all causes for renal insufficiency need to be examined when evaluating stenting outcomes and include contrast nephropathy, progression of underlying disease, reperfusion injury and atheroembolization.11
Several trials have attempted to address concerns by incorporating different types of embolic protection devices such as the GuardWire™ (Medtronic, Inc., Minneapolis, Minnesota) and the FilterWire™ (Boston Scientific Corp., Natrick, Massachusetts). Results from several small, singlecenter investigations suggest that in most cases, material can be removed and improvement seen in renal function roughly 40% of the time, with no acute deterioration. A recent National Institutes of Health (NIH)-funded investigation will further study the effect of renal intervention on hypertension, renal function and reduction in cardiovascularrelated events. This study, titled the CORAL trial, will compare optimal medical therapy (OMT) alone to OMT plus stent revascularization. All patients will receive ARB (candesartan), as well as medications according to the guidelines related to LDL, HTN and HbA1c control. Patients randomized to receive stents will be treated with the Genesis stent (Cordis Corp., Miami Lakes, Florida) and placement will be conducted using the AngioGuard™ (Cordis) distal protection system. The trial enrollment goal is 1,080 patients and endpoints include death (related to either cardiovascular or renal disease), stroke, myocardial infarction, hospitalization for congestive heart failure, progressive renal insufficiency or need for renal replacement therapy. Figure 1 displays a schematic of this investigation. The CORAL trial represents an important step in the evaluation of renal artery stenting, since patients will not be randomized to placebo; in fact, the control group will receive optimal medical therapy, thus providing Class I evidence related to renal artery stenting.
Conclusions and next steps. Results of early investigations and intentions for ongoing trials suggest that embolic protection is an important consideration for renal interventions, and not a strategy reserved only for carotid or saphenous vein graft intervention. There is no strategy for early bifurcation or in very large vessels, which perhaps cannot be sufficiently protected with the various symptoms and systems. We propose using the Protechtor Device (Chanhassen, Minnesota), which may be one approach.
Renal artery angiography and stenting requires careful patient evaluation and standardized and consistent physician preparation in order to avoid the appearance of “drive-by” intervention. The patient should have indications for renal arteriography to include failure of medical therapies, specifically, 3-drug therapy, continued hypertension or progression of renal insufficiency or noninvasive testing suggesting significant renal artery stenosis. Such careful study in comparison to medical therapy will allow renal and other percutaneous transluminal angioplasty-type procedures to withstand the scrutiny of scientific and regulatory bodies. It is clear that interventional devices now require randomized trials, and no longer just noninferiority trials, but superiority trials as well.
By returning to basics, including careful training, certification and documentation for renal artery intervention, it may be possible to restore confidence in interventional techniques. After 30 years of performing renal angioplasty, we now know the technique may improve hypertension, but we are being challenged by governmental agencies as well as other practitioners to document its value compared to medical therapy. Embolic protection may be important, perhaps more than we realize; however, industry and thoughtleaders need to explore better products to treat renal artery stenosis.
1. Mahler F, Krneta A, Haertel M. Treatment of renovascular hypertension by transluminal renal artery dilatation. Ann Internal Med 1979;90:56–57.
2. Gruentzig A, Kuhl Mann U, Vetter W, et al. Treatment of renovascular hypertension with percutaneous transluminal dilation of a renal-artery stenosis. Lancet 1978;1:801–802.
3. Bates MC, Campbell JE, Stone PA, et al. Factors affecting long-term survival following renal artery stenting. Catheter Cardiovasc Interv 2007;69:1037–1043.
4. Van Jaarsveld BC, Deinum J. Evaluation and treatment of renal artery stenosis: Impact on blood pressure and renal function. Curr Opin Nephrol Hypertens 2001;10:399–404.
5. Webster J, Marshall F, Abdalla M, et al. Randomised comparison of percutaneous angioplasty vs. continued medical therapy for hypertensive patients with atheromatous renal artery stenosis. Scottish and Newcastle Renal Artery Stenosis Collaborative Group. J Hum Hypertens 1998;12:329–335.
6. Plouin PF, Chatellier G, Darne B, Raynaud A. Blood pressure outcome of angioplastry in atherosclerotic renal artery stenosis: A randomized trial. Essai Multicentrique Medicaments vs Angioplastie (EMMA) Study Group. Hypertension 1998;31:9823–9829.
7. Nordmann A, Logan AG. Balloon angioplasty versus medical therapy for hypertensive patients with renal artery obstruction. Cochrane Database Systematic Review 2003;3:CD002944.
8. Lederman RJ, Mendelsohn FO, Santos R, et al. Primary renal artery stenting: Characteristics and outcomes after 363 procedures. Am Heart J 2001;142:314–323.
9. Rocha-Singh K, Jaff MR, Rosenfield K, for the ASPIRE-2 Trial Investigators. Evaluation of the safety and effectiveness of renal artery stenting after unsuccessful balloon angioplasty: The ASPIRE-2 study. J Am Coll Cardiol 2005;46:776–783.
10. Sapoval M, Zahringer M, Pattynama P, et al. Low-profile stent system for treatment of atherosclerotic renal artery stenosis: The GREAT trial. J Vasc Interv Radiol 2005;16:1195–1202.
11. Zahringer M, Sapoval M. Pattynama PM, et al. Sirolimus-eluting versus bare-metal low-profile stent for renal artery treatment (GREAT Trial): Angiographic follow-up after 6 months and clinical outcome up to 2 years. J Endovasc Ther 2007;14:460–468.