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.
Stenting may not improve renal function
Coincidental renal artery stenosis in a patient with unrelated chronic kidney disease is very hard to differentiate from true ischemic nephropathy. Furthermore, most patients with ischemic nephropathy do not benefit from revascularization, making it challenging to identify those few whose renal function may respond.
Given that patients with chronic kidney disease tend to have a higher risk of cardiovascular disease, it is not surprising that 15% of them may have renal artery stenosis,4 most often incidental.
Chábová40 examined the outcomes of 68 patients who had chronic kidney disease and a renal artery lesion larger than 70% who did not undergo angioplasty. In only 10 (15%) of the patients did the glomerular filtration rate (GFR) decline by more than 50% of its baseline value during the study period of 3 years. Given the retrospective nature of the study, it cannot be determined (and is rather unlikely) that ischemic nephropathy was the cause of the decline in kidney function in all 10 patients.
In a prospective cohort study in 304 patients with chronic kidney disease and renal artery stenosis who underwent surgical revascularization, Textor4 reported that the serum creatinine level showed a meaningful improvement afterward in 28%, worsened in 19.7%, and remained unchanged in 160 52.6%. (A “meaningful” change was defined as > 1.0 mg/dL.) Findings were similar in a cohort that underwent stenting.33
Davies et al41 found that 20% of patients who underwent renal stenting had a persistent increase in serum creatinine of 0.5 mg/dL or more. These patients were nearly three times more likely (19% vs 7%) to eventually require dialysis, and they had a lower 5-year survival rate (41% vs 71%).
Zeller et al39 found that renal function improved slightly in 52% of patients who received stents. The mean decrease in serum creatinine in this group was 0.22 mg/dL. However, the other 48% had a mean increase in serum creatinine of 1.1 mg/dL.
From these data we can conclude that, in an unselected population with renal artery stenosis, stenting provides no benefit to renal function, and that the risk of a worsening of renal function after intervention is roughly equal to the likelihood of achieving any benefit.
Other predictors of improvement in renal function have been proposed, but the evidence supporting them has not been consistent. For example, although Radermacher et al42 reported that a renal resistive index (which reflects arterial stiffness downstream of the stenosis) lower than 0.8 predicted a response in renal function, this finding has not been reliably reproduced.43,44 Similarly, while several studies suggest that patients with milder renal dysfunction have a higher likelihood of a renal response,45,46 other studies suggest either that the opposite is true39 or that baseline renal function alone has no impact on outcome.47
In addition, once significant renal atrophy occurs, revascularization may not help much, since irreversible sclerosis has developed. Thus, the goal is to identify kidneys being harmed by renal artery stenosis during the ischemic phase, when the tissue is still viable.
Unfortunately, we still lack a good renal stress test—eg, analogous to the cardiac stress test—to diagnose reversible ischemia in the kidney. The captopril renal scan has that capability but is not accurate in patients with bilateral stenosis or a GFR less than 50 mL/min, severely limiting its applicability.26 Newer technologies such as blood-oxygen-level-dependent (BOLD) magnetic resonance imaging are being investigated for such a role.48
Cohort studies in patients with declining renal function
In several case series, patients whose renal function had been declining before intervention had impressive rates of better renal function afterward.33,39,47,49–54 In a prospective cohort study by Muray et al,47 a rise in serum creatinine of more than 0.1 mg/mL/month before intervention seemed to predict an improvement in renal function afterward.
One would expect that, for renal function to respond to intervention, severe bilateral stenosis or unilateral stenosis to a solitary functioning kidney would need to be present. However, this was an inconsistent finding in these case series.33,39,47,52,53 The Angioplasty and Stent for Renal Artery Lesions (ASTRAL) trial,6,7 discussed later, sheds a bit more light on this.
Stenting usually improves flash pulmonary edema
Acute pulmonary edema in the setting of bilateral renal artery stenosis seems to be a unique case in which improvement in clinical status can be expected in most patients after intervention. Blood pressure improves in 94% to 100% of patients,28,31 renal function either improves or stabilizes in 77% to 91%,28–31 and pulmonary edema resolves without recurrence in 77% to 100%.28–30
NEW RANDOMIZED TRIALS: STAR, ASTRAL, AND CORAL
Despite the lack of evidence supporting revascularization of renal artery stenosis, many interventionalists practice under the assumption that the radiographic finding of renal artery stenosis alone is an indication for renal revascularization. Only three randomized controlled trials in the modern era attempt to examine this hypothesis: STAR, ASTRAL, and CORAL.
STAR: No clear benefit
The Stent Placement and Blood Pressure and Lipid-lowering for the Prevention of Progression of Renal Dysfunction Caused by Atherosclerotic Ostial Stenosis of the Renal Artery (STAR) trial5 was a European multicenter trial that enrolled 140 patients with ostial renal artery stenosis greater than 50%, blood pressure controlled to less than 140/90 mm Hg, and creatinine clearance 15 to 80 mL/min.
Patients were randomized to undergo stenting or medical therapy alone. High blood pressure was treated according to a protocol in which angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers were relegated to second-line use. All patients received a statin, regardless of lipid levels.
At 2 years, the primary end point (a decline in creatinine clearance of 20% or greater) had been reached in 10 (16%) of the 64 patients in the stent group and 16 (22%) of the 76 patients in the medication group; the difference was not statistically significant (hazard ratio 0.73, 95% confidence interval 0.33–1.61). No difference was seen in the secondary end points of the degree of blood pressure control or the rates of cardiovascular morbidity and death.5
