Stenting atherosclerotic renal arteries: Time to be less aggressive
ABSTRACTPercutaneous intervention has become very popular for treating atherosclerotic renal artery stenosis, as the use of stents has boosted the rate of technical success and as more cases are being discovered incidentally during angiography of the coronary or other arteries. Yet randomized trials indicate that the procedure does little in terms of controlling blood pressure and may actually harm as many patients as it helps in terms of renal function. Needed are better ways to predict which patients will benefit and better ways to prevent adverse effects such as atheroembolism.
KEY POINTS
- Two large randomized trials of intervention vs medical therapy showed negative results for intervention. A third trial is under way.
- Intervention is not recommended if renal function has remained stable over the past 6 to 12 months and if hypertension can be controlled medically.
- The best evidence supporting intervention is for bilateral stenosis with “flash” pulmonary edema, but the evidence is from retrospective studies.
- Stenosis by itself, even if bilateral, is not an indication for renal artery stenting.
FOUR CLINICAL PRESENTATIONS OF RENAL ARTERY STENOSIS
Renal artery stenosis can present in one of four ways:
Clinically silent stenosis. Because renal artery stenosis is most often found in older patients, who are more likely to have essential hypertension and chronic kidney disease due to other causes, it can be an incidental finding that is completely clinically silent.16,25
Renovascular hypertension is defined as high blood pressure due to up-regulation of neurohormonal activity in response to decreased perfusion from renal artery stenosis. Renal artery stenosis is estimated to be the cause of hypertension in only 0.5% to 4.0% of hypertensive patients, or in 26% of patients with secondary hypertension.3
Ischemic nephropathy is more difficult to define because ischemia alone rarely explains the damage done to the kidneys. Activation of neurohormonal pathways and microvascular injury are thought to contribute to oxidative stress and fibrosis.26 These phenomena may explain why similar degrees of stenosis lead to varying degrees of kidney damage in different patients and why the severity of stenosis does not correlate with the degree of renal dysfunction.27
Furthermore, stenosis may lead to irreversible but stable kidney damage. It is therefore not surprising that, in studies in unselected populations (ie, studies that included patients with all presentations of renal artery stenosis, not just those more likely to benefit), up to two-thirds of renal interventions yielded no clinical benefit.25
As a result, if we define ischemic nephropathy as renal artery stenosis with renal dysfunction not attributable to another cause, we probably will overestimate the prevalence of ischemic nephropathy, leading to overly optimistic expectations about the response to revascularization.
Recurrent “flash” pulmonary edema is a less common presentation, usually occurring in patients with critical bilateral renal artery stenosis or unilateral stenosis in an artery supplying a solitary functioning kidney. Most have severe hypertension (average systolic blood pressure 174–207 mm Hg) and poor renal function.28–30
The association between pulmonary edema and bilateral renal artery stenosis was first noted in 1998 by Pickering et al,31 who in several case series showed that 82% to 92% of patients with recurrent pulmonary edema and renal artery stenosis had bilateral stenosis, compared with 20% to 65% of those with other presentations. Later case series corroborated this finding: 85% to 100% of patients with renal artery stenosis and pulmonary edema had bilateral stenosis.28–30
STENTING IS NOW STANDARD
Stenting has become standard in the endovascular treatment of renal artery stenosis.
Most atherosclerotic renal artery lesions are located in the ostium (ie, where the artery branches off from the aorta), and many are extensions of calcified aortic plaque.26,32 These hard lesions tend to rebound to their original shape more often with balloon angioplasty alone. Stenting provides the additional force needed to permanently disrupt the lesion, leading to a longer-lasting result.
Rates of technical success (dilating the artery during the intervention) are higher with stents than without them (98% vs 46%– 77%).33,34 If the lesion is ostial, this difference is even more impressive (75% vs 29%). In addition, restenosis rates at 6 months are lower with stents (14% vs 26%–48%).34
GOALS: LOWER THE BLOOD PRESSURE, SAVE THE KIDNEY
Because endovascular procedures pose some risk to the patient, it is critical to intervene only in patients most likely to respond clinically. The decision to intervene depends largely on the clinical goal, which should depend on the clinical presentation.
However, if renal artery stenosis is clinically silent, most of the evidence suggests that intervention has no benefit. Furthermore, although retrospective studies have indicated that intervention may improve survival rates,35,36 prospective studies have not. Similarly, studies have not shown that intervention generally improves cardiovascular outcomes, even though renal artery stenosis is associated with cardiovascular risk.
Hypertension plus stenosis is not necessarily renovascular hypertension
Essential hypertension and clinically silent renal artery stenosis often coexist, which is why blood pressure control often does not improve after stenting. Also, essential hypertension often coexists with renovascular hypertension.37 In this situation, stenting may not eliminate the need for antihypertensive drugs, although it may improve blood pressure control and decrease the drug burden.
Before stents came into use, several randomized controlled trials found that blood pressure was no better controlled after angioplasty, 2,3,38 except in cases of bilateral stenosis.2 This may be because stenosis tended to recur after angioplasty without stents.
The 2000 Dutch Renal Artery Stenosis Intervention Cooperative (DRASTIC) study was the first randomized controlled trial to examine the effect of angioplasty on blood pressure control in renal artery stenosis.38 It had significant design flaws. For example, many patients crossed over from the medical management group to the intervention group because their hypertension was resistant to medical therapy. Overall, intervention (balloon angioplasty without stents in 54 of 56 patients, with stents in the other 2) carried no benefit. However, in subgroup analysis, the patients who crossed over because of resistant hypertension (failure of a three-drug regimen) were more likely to benefit from angioplasty. This suggested that risk stratification should take place early on, before proceeding with revascularization.
With stents, Zeller,39 in a prospective nonrandomized study, found that the mean arterial pressure decreased by 10 mm Hg. Randomized trials (see below) have failed to demonstrate such a benefit.
