Embolization — A Pathological Mechanism in Renal Artery Stenosis

Renal artery stenosis is a serious disease that is associated with high rates of cardiovascular morbidity and mortality. It has been believed that severe renal artery stenosis contributes to hypertension and renal dysfunction and that these are the primary mechanisms behind the adverse sequelae of renal artery stenosis. In addition, the presence of renal artery stenosis serves as a marker for significant atherosclerosis elsewhere. While this has been the traditional view of renal artery stenosis, there is evidence that embolization may also play an important role. Already, embolization has been recognized as central in acute coronary syndromes and percutaneous coronary intervention, and it is logical to think this would be the case with atherosclerotic renal disease as well.^1–3 In a study of patients undergoing surgical revascularization of renal artery stenosis, 36% of patients were seen to have evidence of prior atheromatous embolization on biopsy.⁴ These patients with evidence of atheroembolization did substantially worse than those without such evidence, including higher rates of mortality. Thus, embolization is common, ongoing and associated with increased risk. Potentially, then, in the patient with renal artery stenosis, merely controlling blood pressure with medical therapy may actually allow embolization to continue from the persistent presence of a nidus for embolization. While heretical at first glance, it may in fact be true that maximal antihypertensive therapy in the absence of revascularization may “mask” the detrimental effects of renal artery stenosis, or at least that component due to embolization. Indeed, in this issue of the Journal of Invasive Cardiology, Dorros et al. have provided evidence supportive of this heretical concept. In 544 patients (quite a large series by peripheral interventional standards), Dorros et al. demonstrated that there was stabilization of renal function after renal stenting, as assessed by the reciprocal of serum creatinine. This elegant work adds to the growing body of retrospective data, which collectively suggest that renal artery stenting stabilizes renal function that would otherwise most probably deteriorate. Furthermore, this study found that patients who had poorly controlled blood pressure as the indication for their procedure actually fared better than those with medically controlled blood pressure at the time of the procedure. Potentially, this represents the consequence of ongoing embolization from a renal artery lesion while attempts are being made medically to control blood pressure. Of course, this hypothesis can only be proven in a randomized trial of patients with renal artery stenosis who are all treated with maximal medical therapy and then randomly assigned to renal artery stenting or not (such a trial, called CORAL, is in the advanced stages of planning). Thus, the paradigm of renal artery stenosis may be somewhat analogous to carotid artery stenosis. Severe stenoses, especially when bilateral, may be hemodynamically significant, but while hemodynamic transient ischemic attacks and strokes may occur, the much more common forms are due to embolization. The Dorros paper may provide the impetus for a complete paradigm shift in our approach to renal artery stenosis. For example, in the future, a severe stenosis may be treated percutaneously, whereas the decision to treat a moderate stenosis percutaneously may depend on whether there is any evidence of embolization, either on clinical grounds (worsening renal function) or based on an imaging study. Of course, this approach remains entirely speculative and further supportive data will be necessary. While spontaneous renal embolization appears to be detrimental, so too must be iatrogenic embolization, as occurs with stenting. Emboli protection devices (EPD) should therefore further improve the results of renal stenting. Already, a number of series of renal stenting with emboli protection have been described, with capture of a large amount of embolic debris.^5,6 The RESIST study is currently randomizing patients undergoing renal stenting to either placebo or the glycoprotein IIb/IIIa inhibitor abciximab and either to receive the Angioguard EPD or not. In my own practice, I currently use EPD in over 50% of renal cases (initially the Percusurge and now the Filterwire). When using distal protection devices, there is a theoretical concern of promoting embolization to the feet with the occlusion balloon systems. While none of the current EPD designs are optimal if there is an early bifurcation or for large-diameter renal arteries, further generations of lower profile devices, with larger diameter filters, will be a major advance. Distal protection devices may not be best suited for situations where there is early branching, but proximal occlusion devices may fill this niche. At the present time, results obtained with renal artery stenting are already excellent.^7–11 Emboli protection devices will likely further enhance the results obtained. Add to this the ongoing work with drug-eluting stents for renal artery stenosis (namely, the GREAT trial randomizing patients to a bare metal stent or a sirolimus-coated stent), which will likely lead to an even lower rate of renal artery stent restenosis, and it is evident that the future of renal artery intervention is bright. Technical refinements in the procedure will likely lower the threshold for recommending renal stenting. Ongoing efforts to enhance detection of renal artery stenosis in patients at risk will further increase the pool of patients who may benefit from renal intervention.¹² Certainly, there are those who are skeptical of renal revascularization, citing dated balloon angioplasty series and poor outcomes, creating a self-fulfilling prophecy in which patients with renal artery stenosis are not treated until too advanced in their disease state to benefit — perhaps, as Dorros et al. surmise, early intervention to prevent ongoing embolization will be the key to treating renal artery stenosis at a stage when patients are most likely to derive benefit.