Guys and St Thomas Trust, London, UK
Correspondence and offprint requests to: John E. Scoble, Guys Hospital, St Thomas Street, London SE1 9RT, UK. Email: john.scoble{at}gstt.sthames.nhs.uk
Keywords: renal angioplasty; renal atherosclerotic vascular disease; stent placement
In renal atherosclerotic vascular disease there is often no firm randomized trial data to guide clinical practice. Nephrologists often have to interpret trial data from other vascular territories. Vascular protection devices are now an issue in the carotid and cardiac territories. Should they have a role in renal atherosclerotic disease?
There is considerable literature on renal atheroembolic disease. The early paper of Thurlbeck and Castleman [1] showed that in post-mortem renal histology analysis after aortic aneurysm repair followed by death there was an incidence of renal atheroembolic disease of >70%. It also showed that there was a >20% incidence of atheroembolic disease in individuals with no intervention but severe aortic atherosclerotic disease. Flory [2] showed that this condition is related to cholesterol crystal embolization to the renal vascular bed and suggested that the vessels occluded were between 55 and 900 µm in diameter. There is also some recent experimental evidence by Kimura et al. [3] using acryl bead microspheres to mimic atheroembolic disease in rats. These microspheres were 2030 µm in diameter and the histological features produced were similar to those with atheroembolic disease in humans. The spheres lodge in the small arterioles and glomeruli. They are probably a little smaller than the cholesterol clefts in vivo that may be 20 µm in diameter but have a greater length. Two important points emerged from this report. The first is that the outcomes in terms of proteinuria and renal dysfunction were dependent on the initial dose of microspheres. Only large doses induced proteinuria and only at the largest dose was there a decline in renal function. This is in keeping with the insidiously progressive form of atheroembolic disease rather than the acute catastrophic form. With low doses of microspheres there was no proteinuria or renal dysfunction. The second important point is that the maximum effect of embolization was only seen at 12 weeks. The important issue from these experimental scenarios is whether there is a doseeffect relationship in atheroembolic disease. Will reducing the dose of atheroembolic debris alter the outcome?
Embolization at angioplasty?
There is an interesting report by Rapp et al. [4] in an ex vivo preparation of carotid vessels with interventions and analysis of the effluent that has shed new light on this issue (Figure 1). The authors showed that the passing of an initial guide wire produced emboli but there was a significant increase with angioplasty and even more with stent placement. There has also been Doppler analysis of cerebral blood flow and microemboli generation during carotid angioplasty and carotid endarterectomy [5]. The signals recorded were interpreted to reflect debris in the carotid circulation. Of note signal registration was much greater in patients having angioplasty rather than in those undergoing surgery. Moreover, there was a relationship between Doppler recognition of emboli and neurological sequelae with a lower incidence of neurological events in the surgery rather than in the angioplasty cohort.
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Embolization and type of procedure
It is well described in a number of articles that a proportion of patients will benefit from angioplasty with or without stent placement [7,8]. At the same time all the series have shown patients who have had a decrement in renal function with this procedure. Single stent glomerular filtration rate estimations before and within 3 months of the procedure showed that a number of kidneys suffer a decline in function after angioplasty [8].
There are three types of protection device from a number of manufacturers [9]. One developed for carotid angioplasty and stent placement involves reversal of blood flow through the carotid during the angioplasty procedure and is not applicable to the renal artery. The second type is a soft balloon inflated distal to the angioplasty/stent placement to occlude the lumen. At the end of the procedure debris is aspirated from the occluded vessel after the removal of the stent placement device. The balloon is then deflated and withdrawn. The third type of device is a filter that is deployed distal to the angioplasty site to catch any fragments that may be dislodged [10]. It is not clear whether this device will catch single cholesterol crystals. It is also clear that manoeuvring these devices into the renal artery may in itself lead to cholesterol embolization.
Studies have shown that there is considerable debris from carotid artery stenting. Angelini et al. [11] using the Angioguard device, which is a filter device, found the particle size ranged from 1.1 to 5044 µm in the major axis and 0.7 to 1175 µm in the minor axis. Debris was detected in 84% of filters. Webb et al. [12] with cardiac saphenous vein graft intervention showed that particulate debris were found in 91% of cases. Particle size was 204 x 83 µm. All these studies show that in any intervention there is release of atheroembolic material of the size shown by Flory [2] to be important.
Stent protection
There is compelling evidence from cardiac stent placement that they are effective. A study by Baim et al. [13], with over 800 patients randomized to stent placement with or without a protective device, showed a significant difference in terms of the defined endpoints (Figure 2). The device used in this study was an occlusive balloon device. There was a significant reduction in the primary endpoint from 16.5 to 9.6% when a protection device was used. The endpoint was a composite of death, myocardial infarction, emergency bypass or target vessel revascularization. These represent very short-term events and there does not appear to be a similar scenario to the progressive dysfunction seen with renal atheroembolic disease. However, this is a major validation of the use of protective devices in the coronary circulation.
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Conclusion and perspective
It is now clear from the new data that atheroemboli are the rule in any intervention in atherosclerotic disease [15]. The lack of frequency of this important clinical outcome is by luck rather than an understanding of the underlying pathophysiological processes or appropriate measures to avoid it. Angioplasty and stent placement will automatically release atheroemboli to the renal circulation. It is also clear that the effect of this cannot be overwhelming, as angioplasty/stent placement can be associated with an improvement in renal function. At the same time, the experimental evidence suggests that there is a dose effect of atheroemboli and that the result after angioplasty may depend on the dose of cholesterol crystals released to the renal circulation. It is unlikely that any device will preclude any cholesterol embolization as the experimental data show that even the guide wire placement will produce this. However, it is also possible that the heterogeneous response of the kidney to angioplasty in patients with atherosclerotic disease, compared with the beneficial response to angioplasty in fibromuscular dysplasia, may depend on the amount of cholesterol crystals released by the procedure. At present neither of the two randomized trials underway in Europe have addressed the issue of protection devices. However, it may be possible for smaller trials with single kidney function measurements to be performed to address this issue. If there were changes in outcome similar to the randomized trial in coronary artery disease then it would be difficult not to use protection devices in routine practice.
Conflict of interest statement. None declared.
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