Correspondence
Revascularization for Renal-Artery Stenosis
N Engl J Med 2010; 362:762-764February 25, 2010
- Article
To the Editor:
The ASTRAL (Angioplasty and Stenting for Renal Artery Lesions) Investigators (Nov. 12 issue)1 found substantial risk but no clinical benefit from revascularization as compared with medical management in patients with atherosclerotic renovascular disease. A total of 806 patients at 57 hospitals were enrolled over the course of 7 years. On average, 2 patients per center per year underwent randomization, which indicates serious selection bias or inexperienced staff at centers with very low intervention rates. This concern is supported by a low rate of technical success (317 of 403 patients [79%] in the revascularization group) and a high rate of serious complication in 23 of 280 patients (8%) as compared with reports in the literature of 98% and 2%, respectively.2 In addition, the study design implies that optimal medical therapy was used to achieve normalized blood pressure in both groups. Thus, not only the blood pressure values but also the number of antihypertensive drugs used to achieve this goal should be taken into account. The issue of selection bias and the significantly lower number of antihypertensive drugs administered in the revascularization group (P=0.03) preclude the definitive conclusion that renal-artery revascularization provides no clinical benefit.
Daniel Staub, M.D.
Heiko Uthoff, M.D.
Kurt A. Jaeger, M.D.
University Hospital Basel, Basel, Switzerland
staubd@uhbs.ch No potential conflict of interest relevant to this letter was reported.
2 References1
The ASTRAL Investigators
Full Text | Web of Science | Medline2
White CJ . Catheter-based therapy for atherosclerotic renal artery stenosis. Circulation 2006;113:1464-1473
CrossRef | Web of Science | Medline
To the Editor:
The results of the ASTRAL investigation should be read and interpreted critically. As with the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, the take-home message should be that for patients with a moderate degree of renal-artery stenosis, medical management is as effective as revascularization over a 5-year follow-up period. Patients seen as requiring anatomical correction were not enrolled; only those deemed suitable for randomization to stenting or medical therapy were included. Thus, the patients most likely to benefit from stenting (those with subocclusive lesions or with very severe disease in one or both kidneys) were not part of this study. These patients should still be treated with renal-artery stenting given no precluding factors. In addition, renal-resistance indexes were not recorded, and the small numbers of high-grade renal stenoses performed did not allow significant findings in that group.
Another concern is the prohibitively high rate of amputation and embolization in this study. This calls into question the appropriateness and safety of the techniques currently used to perform the procedure. In more than 200 consecutive cases in which the technique known as “no touch”1 was used (with a guidewire in the aorta preventing the guide catheter from dislodging aortic plaque), I have not seen amputation, limb ischemia, or any evident embolization.
James R. Wilentz, M.D.
Lenox Hill Heart and Vascular Institute, New York, NY
wilentz@gmail.com No potential conflict of interest relevant to this letter was reported.
1 References1
Feldman RL ,Wargovich TJ ,Bittl JA . No-touch technique for reducing aortic wall trauma during renal artery stenting. Catheter Cardiovasc Interv 1999;46:245-248
CrossRef | Web of Science | Medline
To the Editor:
The results of the ASTRAL study indicate that there is no advantage of revascularization as compared with pharmacotherapy in patients with atherosclerotic renal disease. The primary outcome was the change in renal function, inferred from the reciprocal of the serum level of creatinine. However, serum creatinine is only a rough indicator of the glomerular filtration rate. Furthermore, patients with major indications for revascularization were excluded from the study, whereas patients with either insignificant vascular lesions or advanced renal disease (kidneys 6 cm in length), for whom no benefit from revascularization could be expected, were enrolled. Moreover, intraparenchymal resistance, a relevant predictor of the success of revascularization, was not evaluated.1 Finally, only about 40 to 50% of the patients were treated with drugs that block the pathway of the renin–angiotensin–aldosterone system; the use of such drugs is currently recommended in any patient with atherosclerotic renal-artery stenosis.2 With such methodologic limitations, the ASTRAL study does not offer convincing guidance for clinical practice.
Pasquale Esposito, M.D.
Giovanni Piotti, M.D.
Antonio Dal Canton, M.D.
Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
pasqualeesposito@hotmail.com No potential conflict of interest relevant to this letter was reported.
2 References1
Radermacher J ,Chavan A ,Bleck J , et al. Use of Doppler ultrasonography to predict the outcome of therapy for renal-artery stenosis. N Engl J Med 2001;344:410-417
Full Text | Web of Science | Medline2
Dworkin LD ,Cooper CJ . Renal-artery stenosis. N Engl J Med 2009;361:1972-1978
Full Text | Web of Science | Medline
To the Editor:
A major limitation of the ASTRAL trial was its inclusion of patients whose diagnosis of renal artery stenosis was made on the basis of noninvasive imaging alone. No attempt was made to confirm the severity of stenosis with digital subtraction angiography or to assess its functional significance before randomization. Furthermore, 17% of the patients in the revascularization group did not proceed to revascularization after invasive angiography.
Data suggest that a pressure gradient from the distal renal artery to the aorta of less than 0.90 results in exponential renin release and may be considered the threshold for a functionally significant stenosis.1 In patients with coronary-artery disease, the use of a pressure wire to guide revascularization improves clinical outcomes.2 In the ASTRAL trial, patients had mild hypertension but did not have development of progressive renal dysfunction, which suggests that the majority did not have functionally significant renal-artery disease. We believe there remains a role for revascularization in patients with renal-artery stenosis but that an invasive assessment of functional significance is essential before patients are included in randomized, controlled trials of renal-artery intervention.
2 ReferencesNicholas L. Mills, M.B., Ch.B., Ph.D.
Neeraj Dhaun, M.B., Ch.B.
Neal G. Uren, M.D.
Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
nick.mills@ed. ac. uk 1
De Bruyne B ,Manoharan G ,Pijls NH , et al. Assessment of renal artery stenosis severity by pressure gradient measurements. J Am Coll Cardiol 2006;48:1851-1855
CrossRef | Web of Science | Medline2
Tonino PAL ,De Bruyne B ,Pijls NHJ , et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213-224
Full Text | Web of Science | Medline
Author/Editor Response
We agree that the results of the ASTRAL trial need to be considered carefully in light of its design and enrolled patient population. However, we disagree that there was important selection bias. All patients enrolled in the trial had anatomically significant atherosclerotic renal-artery stenosis and would have been considered for revascularization in normal clinical practice. Lack of reliable evidence regarding the effectiveness of revascularization in this type of patient meant that clinicians were uncertain as to whether they should intervene; consequently, they considered the randomization of these patients into the ASTRAL study to be appropriate. Revascularization outside the trial was considered appropriate for some patients with renal-artery stenosis because of their clinical presentation (e.g., acute kidney injury, acute heart failure) and the consequent uncertainty of the treating physician as to how best to proceed. However, such patients were a minority, with only approximately 25% of patients considered suitable for revascularization outside the trial. The center recruitment rates cited by Staub et al. are misleading: 70% of patients were recruited from just 15 centers (an average of more than five patients per year).
Although the skills of the physicians performing revascularization were not formally assessed, their expertise was reflected in a technical success rate of 95% (not 78%, as cited by Staub et al.). Complication rates often appear higher in trials because of more rigorous recording keeping. Nevertheless, the rate of serious complications in the ASTRAL trial was just 6.4%, similar to or less than that in other methodologically robust studies.1
We also disagree with the methodologic criticisms, which cannot plausibly explain the negative findings of our study. First, the primary end point was the reciprocal of the serum creatinine level, the best available estimate of the glomerular filtration rate (a more precise measure of renal function) before the introduction of the Modification of Diet in Renal Disease (MDRD) formula.2 Second, the use of pressure wires to assess gradients across renal-artery stenosis is not routine in the United Kingdom, and there are no validated data relating gradients to outcomes after revascularization. Similarly, measurement of the intrarenal resistive index is not routine practice in the United Kingdom, and there is no consensus regarding its usefulness and general applicability.3 Third, the slight differences in the number of antihypertensive drugs administered to the two treatment groups and the underutilization of renin–angiotensin blocking agents are insufficient to explain the absence of significant differences between treatments for any trial end point.
In summary, the ASTRAL trial provides reliable evidence that in patients with asymptomatic but significant anatomical renal-artery stenosis (i.e., typical patients presenting with chronic kidney disease and hypertension and considered for revascularization in normal clinical practice), revascularization offers no worthwhile clinical benefit and has some risk. However, we accept that revascularization might benefit a minority of patients with renal-artery stenosis who have specific clinical presentations or anatomical abnormalities.
Philip Kalra, F.R.C.P., M.D.
Salford Royal Hospital, Salford, United KingdomJonathan Moss, F.R.C.R., F.R.C.S.
Gartnavel Hospital, Glasgow, United KingdomNatalie J. Ives, M.Sc.
University of Birmingham, Birmingham, United Kingdom
n.j. ives@bham. ac. uk Since publication of their article, the authors report no further potential conflict of interest.
3 References1
Leertouwer TC ,Gussenhoven EJ ,Bosch JL , et al. Stent placement for renal arterial stenosis: where do we stand? A meta-analysis. Radiology 2000;216:78-85
Web of Science | Medline2
Levey AS ,Bosch JP ,Lewis JB ,Greene T ,Rogers N ,Roth D . A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 1999;130:461-470
Web of Science | Medline3
Krumme B ,Hollenbeck M . Doppler sonography in renal artery stenosis -- does the Resistive Index predict the success of intervention? Nephrol Dial Transplant 2007;22:692-696
CrossRef | Web of Science | Medline
