Atherosclerotic renal artery stenosis and reconstruction
2006; Elsevier BV; Volume: 70; Issue: 9 Linguagem: Inglês
10.1038/sj.ki.5001836
ISSN1523-1755
Autores Tópico(s)Cerebrovascular and Carotid Artery Diseases
ResumoRenal artery stenosis is common especially in patients with generalized atherosclerosis. It is frequently associated with difficult-to-treat hypertension and with renal failure. There is an ongoing debate about the appropriate screening and treatment of atherosclerotic renal artery stenosis. Advances in imaging and interventional devices offer new opportunities, however, clinicians still have to decide individually in every patient to treat or not to treat stenosis with revascularization. This review evaluates the current literature in order to help the physician to find the right decision in this challenging clinical issue. Renal artery stenosis is common especially in patients with generalized atherosclerosis. It is frequently associated with difficult-to-treat hypertension and with renal failure. There is an ongoing debate about the appropriate screening and treatment of atherosclerotic renal artery stenosis. Advances in imaging and interventional devices offer new opportunities, however, clinicians still have to decide individually in every patient to treat or not to treat stenosis with revascularization. This review evaluates the current literature in order to help the physician to find the right decision in this challenging clinical issue. Atherosclerosis is the main cause of renal artery stenosis. The lesions mostly occur in ostial segments of the renal artery and represent extension of adjacent aortic atherosclerotic plaque.1.Textor S. Ischemic nephropathy: where are we now?.J Am Soc Nephrol. 2004; 15: 1974-1982Crossref PubMed Scopus (141) Google Scholar Renovascular disease may induce renovascular hypertension as well as ischemic nephropathy, an increasingly recognized cause of end-stage renal failure in the US.2.Preston R.A. Epstein M. Ischemic renal disease: an emerging cause of chronic renal failure and end-stage renal disease.J Hypertens. 1997; 15: 1365-1377Crossref PubMed Scopus (157) Google Scholar This article will focus on the management and treatment of patients with atherosclerotic renal artery stenosis (ARAS) rather than on patients with fibromuscular dysplasia, which was recently reviewed in depth.3.Slovut D.P. Olin J.W. Fibromuscular dysplasia.N Engl J Med. 2004; 350: 1862-1871Crossref PubMed Scopus (658) Google Scholar Despite extensive research there is still a controversy concerning the appropriate treatment of patients with ARAS. Physicians have to balance for their patients the chances of improvement regarding blood pressure and renal function versus risks and costs of intervention. Efforts have focused on finding reliable clinical parameters as well as improved diagnostic techniques for predicting the outcome of ARAS,4.Krijnen P. van Jaarsfeld B.C. Steyerberg E.W. et al.A clinical prediction rule for renal artery stenosis.Ann Intern Med. 1998; 129: 705-711Crossref PubMed Scopus (181) Google Scholar, 5.Kennedy D.J. Colyer W.R. Brewster P.S. et al.Renal insufficiency as a predictor of adverse events and mortality after renal artery stent placement.Am J Kid Dis. 2003; 42: 926-935Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar, 6.Vasbinder G.B.C. Nelemans P.J. Kessels A.G.H. et al.Diagnostic tests for renal artery stenosis in patients suspected of having renovascular hypertension: a meta-analysis.Ann Intern Med. 2001; 135: 401-411Crossref PubMed Scopus (340) Google Scholar, 7.Binkert C.A. Debatin J.F. Schneider E. et al.Can MR measurement of renal artery flow and renal volume predict the outcome of percutaneous transluminal renal angioplasty?.Cardiovasc Intervent Radiol. 2001; 24: 233-239Crossref PubMed Scopus (57) Google Scholar, 8.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: 410-417Crossref PubMed Scopus (669) Google Scholar however, ideal solutions have not yet been found. It is of note, that ARAS may occur alone (isolated anatomical renal artery stenosis) or in association with hypertension, renal insufficiency (ischemic nephropathy), or both.9.Safian R.D. Textor S. Renal-artery stenosis.N Engl J Med. 2001; 344: 431-442Crossref PubMed Scopus (900) Google Scholar Hence screening tests for ARAS as well as interventional procedures have to be discussed in the light of the outcome of renovascular hypertension and ischemic nephropathy. Additionally it is worth taking in consideration the high cardiovascular mortality of patients with ARAS and its potential pathophysiological background. At present it is uncertain, whether renovascular reconstruction can improve the high mortality of these patients. Patients with ARAS are mainly older than 60 years and frequently suffer from widespread coexistent vascular disease. Five-year-survival has been found to be as low as 45% in patients with bilateral ARAS,10.Babool K. Evans C. Moore R.H. Incidence of end-stage renal disease in medically treated patients with severe bilateral atherosclerotic renovascular disease.Am J Kidney Dis. 1998; 31: 971-977Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar decreasing to only 18% in those requiring dialysis therapy.11.Mailloux L.U. Napolitano B. Belluci A.G. et al.Renal vascular disease causing end-stage renal disease, incidence, clinical correlates, and outcomes: a 20-year clinical experience.Am J Kidney Dis. 1994; 24: 622-629Abstract Full Text PDF PubMed Scopus (374) Google Scholar In clinical practice it is essential to select patients with a high likelihood of ARAS for the further screening. A clinical score, developed by Krijnen et al.,4.Krijnen P. van Jaarsfeld B.C. Steyerberg E.W. et al.A clinical prediction rule for renal artery stenosis.Ann Intern Med. 1998; 129: 705-711Crossref PubMed Scopus (181) Google Scholar may help in patient selection. However, it is of note, that this score was evaluated in a pre-selected population with a high probability of ARAS, because only those patients with refractory hypertension or an increase of creatinine after therapy with angiotensin-converting enzyme inhibitors were included into the study.4.Krijnen P. van Jaarsfeld B.C. Steyerberg E.W. et al.A clinical prediction rule for renal artery stenosis.Ann Intern Med. 1998; 129: 705-711Crossref PubMed Scopus (181) Google Scholar This bias may have influenced the prevalence of ARAS, evaluated with this score. Nevertheless, it seems useful to rely on several clinical parameters, which increase the likelihood for patients to have ARAS (Table 1). It is of note, that smoking as well as a low body mass index less than 25 kg/m2 are predisposing factors for ARAS.4.Krijnen P. van Jaarsfeld B.C. Steyerberg E.W. et al.A clinical prediction rule for renal artery stenosis.Ann Intern Med. 1998; 129: 705-711Crossref PubMed Scopus (181) Google ScholarTable 1Clinical findings compatible with atherosclerotic renal artery stenosisHypertension Abrupt onset of hypertension at or after the age of 50 years Accelerated or malignant hypertension Refractory hypertension (not responsive to therapy with ≥3 drugs)Renal abnormalities Unexplained azotemia Azotemia induced by treatment with an ACE inhibitor Sonographic length of the kidney <8 cmOther findings Unexplained congestive heart failure or acute pulmonary edema Abdominal bruit, flank bruit, or both Systemic atherosclerotic vascular disease Severe retinopathy Current or former smoker Low body mass index (<25 kg/m2)ACE, angiotensin-converting enzyme. Open table in a new tab ACE, angiotensin-converting enzyme. Meanwhile several non-invasive tests, such as captopril test, color duplex sonography, captopril scintigraphy, computed tomography angiography, and magnetic resonance (MR) angiography are available, most with excellent accuracy. Intra-arterial angiography including the measurement of the pressure gradient is still the gold standard for the diagnosis of ARAS, however, the diagnostic accuracy of even this invasive procedure is also operator dependent.12.Van Jaarsfeld B.C. Pietermann H. van Dijk L.C. et al.Inter-observer variability in the angiographic assessment of renal artery stenosis.J Hypertens. 1999; 17: 1731-1736Crossref PubMed Scopus (66) Google Scholar,13.Paul J.F. Cherrak I. Jaulent M.C. et al.Inter-observer variability in the interpretation of renal digital subtraction angiography.Am J Roentgenol. 1999; 173: 1285-1288Crossref PubMed Scopus (28) Google Scholar Usually renal arteriography is only indicated, if angioplasty or stenting is intended. Recently in a meta-analysis Vasbinder et al.6.Vasbinder G.B.C. Nelemans P.J. Kessels A.G.H. et al.Diagnostic tests for renal artery stenosis in patients suspected of having renovascular hypertension: a meta-analysis.Ann Intern Med. 2001; 135: 401-411Crossref PubMed Scopus (340) Google Scholar compared color duplex sonography with other non-invasive tests by analyzing the area under the receiver operator curve of these screening tests. They found computed tomography angiography and MR angiography with higher diagnostic accuracy than color duplex sonography for the diagnosis of ARAS. Captopril scintigraphy and captopril test were less accurate than color duplex sonography in this meta-analysis. However, diagnostic accuray may be only one of several arguments, which lead the clinician to his favorite screening method. Other criteria may be local availability of the test and personal experience with it, as well as aspects of cost benefit. There are some clear advantages for using color duplex sonography as the first screening test of ARAS. Sonography is an economic test, giving information about the hemodynamic significance of stenosis and avoiding nephrotoxic contrast media. In addition it is useful for the follow-up after renal artery stenting.14.Krumme B. Blum U. Schwertfeger E. et al.Diagnosis of renovascular disease by intra- and extrarenal Doppler scanning.Kidney International. 1996; 50: 1288-1292Abstract Full Text PDF PubMed Scopus (150) Google Scholar,15.Blum U. Krumme B. Flügel P. et al.Treatment of ostial renal-artery stenoses with vascular endoprostheses after unsuccessful ballon angioplasty.N Engl J Med. 1997; 336: 459-465Crossref PubMed Scopus (521) Google Scholar If direct visualization of the renal arteries (Figure 1) is combined with intrarenal scanning of the kidney, both accessible within 30 min of examination time, color duplex sonography has a sensitivity and specificity of 90%, respectively, which is appropiate for a single screening test for ARAS.16.Krumme B. Renal Doppler sonography – update in clinical nephrology.Nephron Clin Pract. 2006; 103: c24-c28Crossref PubMed Scopus (83) Google Scholar Currently, it is at issue whether or not color duplex sonography is useful to predict the outcome of revascularization of ARAS.17.White C.J. Catheter-based therapy for atherosclerotic renal artery stenosis.Circulation. 2006; 113: 1464-1473Crossref PubMed Scopus (105) Google Scholar,18.Krumme B, Hollenbeck M. Doppler sonography in renal artery stenosis – does it predict the success of intervention? Nephrol Dial Transplant (in press).Google Scholar A single study showed a high predictive value of resistive index, obtained in the segmental renal arteries with color duplex sonography,8.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: 410-417Crossref PubMed Scopus (669) Google Scholar however, subsequent studies could not confirm these results.19.Zeller T. Muller C. Frank U. et al.Stent angioplasty of severe atherosclerotic ostial renal artery stenosis in patients with diabetes mellitus and nephrosclerosis.Catheter Cardiovasc Intervent. 2003; 58: 510-515Crossref PubMed Scopus (107) Google Scholar, 20.Soulez G. Therasse E. Qanadli S.D. et al.Prediction of clinical response after renal angioplasty: respective value of renal Doppler sonography and scintigraphy.Am J Roentgenol. 2003; 181: 1029-1035Crossref PubMed Scopus (41) Google Scholar, 21.Garcia-Criado A. Gilabert R. Nicolau C. et al.Value of Doppler sonography for predicting clinical outcome after renal artery revascularization in atherosclerotic renal artery stenosis.J Ultrasound Med. 2005; 24: 1641-1647PubMed Google Scholar High operator dependency of color duplex sonography is often felt to argue against this diagnostic tool in the screening for ARAS. This argument, however, is referring to data of the older literature, when high-end sonographic machines with better penetration of the Doppler beam and faster hardware were not available.22.Chonchol M. Linas S. Diagnosis and management of ischemic nephropathy.Clin J Am Soc Nephrol. 2006; 1: 172-181Crossref PubMed Scopus (31) Google Scholar,23.Spieß K.P. Fobbe F El-Bedewi M. et al.Color-coded duplex sonography for noninvasive diagnosis and grading of renal artery stenosis.Am J Hypertens. 1995; 8: 1222-1231Crossref PubMed Scopus (38) Google Scholar Thus in recent years the success rate of sonographic visualization of the renal arteries has improved owing to further technical improvements as well as owing to broader operator experience. Additionally it is of note, that other renal imaging techniques, such as computed tomography angiography, and MR angiography, also show substantial operator dependency including the gold standard, as mentioned above.12.Van Jaarsfeld B.C. Pietermann H. van Dijk L.C. et al.Inter-observer variability in the angiographic assessment of renal artery stenosis.J Hypertens. 1999; 17: 1731-1736Crossref PubMed Scopus (66) Google Scholar,13.Paul J.F. Cherrak I. Jaulent M.C. et al.Inter-observer variability in the interpretation of renal digital subtraction angiography.Am J Roentgenol. 1999; 173: 1285-1288Crossref PubMed Scopus (28) Google Scholar Recently Vasbinder et al.24.Vasbinder G.B.C. Nelemans P.J. Kessels A.G.H. et al.Accuracy of computed tomographic angiography and magnetic resonance angiography for diagnosing renal artery stenosis.Ann Intern Med. 2004; 141: 674-682Crossref PubMed Scopus (303) Google Scholar prospectively assessed the diagnostic validity of computed tomography angiography and MR angiography with two panels of three observers in 356 hypertensive patients who underwent digital subtraction angiography for detection of renal artery stenosis. Moderate interobserver agreement was found, with K values ranging from 0.59 to 0.64 for computed tomography angiography and 0.40 to 0.51 for MR angiography. Owing to the lack of clear evidence in the literature for diagnostic superiority of one technique, the physician, who has to screen patients for ARAS, will choose this technique, he is either performing himself (e.g., color duplex sonography) or that is easily available, reliable, and valid in his personal experience. Many nephrologists tend to be conservative towards reconstruction of ARAS as some disappointing results were published in three randomized prospective studies, which compared medical treatment with angioplasty in patients with ARAS.25.van Jaarsfeld B. Krijnen P. Pieterman H. et al.The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis.N Engl J Med. 2001; 342: 1007-1014Crossref Scopus (811) Google Scholar, 26.Plouin P.F. Chatellier G. Darne B. et al.Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis: a randomized trial.Hypertension. 1998; 31: 823-829Crossref PubMed Scopus (565) Google Scholar, 27.Webster J. Marshall F. Abdalla M. et al.Randomised comparison of percutaneous angioplasty vs continued medical therapy for hypertensive patients with atheromatous renal artery stenosis.J Hum Hypertens. 1998; 12: 329-335Crossref PubMed Scopus (491) Google Scholar In all three studies there is no evidence that angioplasty improves the outcome of blood pressure in comparison to medical treatment. However, if the clinician prefers medical treatment, the natural history of ARAS has to be considered. It is of note that the progression of ARAS depends on the grading of stenosis at the time of the initial diagnosis. Caps et al.28.Caps M.T. Perissinotto C. Zierler R.E. et al.Prospective study of atherosclerotic disease progression in the renal artery.Circulation. 1998; 98: 2866-2872Crossref PubMed Scopus (359) Google Scholar monitored patients with ARAS by color duplex sonography during a 3-year follow-up. Progressive narrowing was reported in 18, 28, and 49% for renal arteries that initially were classified as normal, 70 years) with an increased risk of cardiovascular and cholesterol-embolic complications during surgical repair of the renal artery. Nevertheless even younger patients with complex renovascular diseases, for example, renal artery aneurysm or failed endovascular procedures, still have a benefit from renal artery surgery. As the introduction of stents patients with ostial ARAS, frequently showing the problem of elastic recoil after angioplasty, should be treated by primary stent placement.15.Blum U. Krumme B. Flügel P. et al.Treatment of ostial renal-artery stenoses with vascular endoprostheses after unsuccessful ballon angioplasty.N Engl J Med. 1997; 336: 459-465Crossref PubMed Scopus (521) Google Scholar However, it is of note that a prospective randomized study comparing renal artery stenting with angioplasty alone at 6 months follow-up did not show any difference of blood pressure outcome between both groups, although the primary patency rate was significantly improved in the patients with stents (75 versus 29%, respectively).36.Van de Ven P.F.G. Kaatee R. Beutler J.J. et al.Arterial stenting and balloon angioplasty in ostial atherosclerotic renovascular disease: a randomised trial.Lancet. 1999; 353: 282-286Abstract Full Text Full Text PDF PubMed Scopus (569) Google Scholar Three single randomized trials did not find any beneficial effect of angioplasty concerning the outcome of blood pressure in comparison to medical treatment.25.van Jaarsfeld B. Krijnen P. Pieterman H. et al.The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis.N Engl J Med. 2001; 342: 1007-1014Crossref Scopus (811) Google Scholar, 26.Plouin P.F. Chatellier G. Darne B. et al.Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis: a randomized trial.Hypertension. 1998; 31: 823-829Crossref PubMed Scopus (565) Google Scholar, 27.Webster J. Marshall F. Abdalla M. et al.Randomised comparison of percutaneous angioplasty vs continued medical therapy for hypertensive patients with atheromatous renal artery stenosis.J Hum Hypertens. 1998; 12: 329-335Crossref PubMed Scopus (491) Google Scholar However, two meta-analyses of these studies, each involving a total of 210 patients, both found a significantly better reduction of blood pressure with angioplasty, rather than with medical treatment.34.Nordmann A.J. Woo K. Parkes R. et al.Ballon angioplasty or medical therapy for hypertensive patients with atherosclerotic renal artery stenosis? A meta-analysis of randomized controlled trials.Am J Med. 2003; 114: 44-50Abstract Full Text Full Text PDF PubMed Scopus (177) Google Scholar,37.Ives N.J. Wheatley K. Stowe R.L. et al.Continuing uncertainty about the value of percutaneous revascularization in atherosclerotic renovascular disease: a meta-analysis of randomized trials.Nephrol Dial Transplant. 2003; 18: 298-304Crossref PubMed Scopus (128) Google Scholar It can be hypothesized that the number of patients in each randomized trial was to low to show any difference of both treatments. For the daily practice, perhaps, we can learn something from important details of the DRASTIC study. From 50 patients originally assigned for drug therapy 22 patients underwent angioplasty after 3 months, because diastolic blood pressure was 95 mm Hg or higher despite treatment with three or more antihypertensive drugs.25.van Jaarsfeld B. Krijnen P. Pieterman H. et al.The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis.N Engl J Med. 2001; 342: 1007-1014Crossref Scopus (811) Google Scholar At this time, before angioplasty was performed in the 22 patients, systolic and diastolic blood pressure as well as the number of antihypertensives were statistically different from those of the 28 patients, who exclusively received medical treatment. After 12 months the final intention-to-treat-analysis of the entire group of 50 patients showed no difference of blood pressure, which may have been influenced by the changes of treatment. These data clearly demonstrate that even those patients with intractable hypertension may have a high likelihood of benefit from reconstruction of the renal artery. Significant ARAS potentially increases the risk of renal atrophy as well as progressive loss of renal function. In none of the three prospective randomized studies there was any consistent change in renal function between the angioplasty and medical-therapy groups.25.van Jaarsfeld B. Krijnen P. Pieterman H. et al.The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis.N Engl J Med. 2001; 342: 1007-1014Crossref Scopus (811) Google Scholar, 26.Plouin P.F. Chatellier G. Darne B. et al.Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis: a randomized trial.Hypertension. 1998; 31: 823-829Crossref PubMed Scopus (565) Google Scholar, 27.Webster J. Marshall F. Abdalla M. et al.Randomised comparison of percutaneous angioplasty vs continued medical therapy for hypertensive patients with atheromatous renal artery stenosis.J Hum Hypertens. 1998; 12: 329-335Crossref PubMed Scopus (491) Google Scholar However, evaluation of renal function was not the primary end point and probably the follow-up of the mentioned studies (6–12 months) was too short to detect any difference. Additionally it is noteworthy that patients with severe renal dysfunction were excluded in all three studies. The slope of decline of the glomerular filtration rate in the recent history of patients with ARAS seems to be more important rather than the level of renal function at the time of admission. Beutler et al.38.Beutler J.J. van Ampting J.M.A. van de Ven P.J.G. et al.Long-term effects of arterial stenting on kidney function for patients with ostial atherosclerotic renal artery stenosis and renal insufficiency.J Am Soc Nephrol. 2001; 12: 1475-1481PubMed Google Scholar prospectively studied the long-term effects of stenting on kidney function in patients with renal insufficiency and ostial ARAS. During a 1-year follow-up in 26 of 56 patients with previous stable renal dysfunction renal artery stenting did not improve serum creatinine levels. However, in the remaining 30 patients with previously deteriorating renal function serum creatinine significantly improved after stenting und remained stable during follow-up monitoring. In another group of patients with global renovascular obstruction (bilateral stenosis or ARAS in the presence of a solitary or single functioning kidney) the previously negative slope of reciprocal serum creatinine became positive in 18 of 33 patients and less negative in additional seven patients.39.Watson P.S. Hadjipetrou P. Cox S.V. et al.Effect of renal artery stenting on renal function and size in patients with atherosclerotic renovascular disease.Circulation. 2000; 102: 1671-1677Crossref PubMed Scopus (259) Google Scholar In conclusion the change of serum creatinine, especially in the recent patient's history, is rather more important for the physician than the absolute level of kidney function. Atherosclerotic renovascular disease, commonly seen in clinical practice, is in part a progressive disorder associated with increased cardiovascular morbidity and mortality. Physicians have to distinguish patients with a high likelihood of treatment benefit from those with incidental ARAS. Answers on the following issues may help the clinician to find the right decision for his individual patient with ARAS: Is there any hypertension that is in fact refractory to antihypertensive treatment? What is the slope of renal function in the recent patient's history? Does the regular non-invasive monitoring show progression of renal artery disease? Further prospective randomized studies, such as the recently started ‘cardiovascular outcomes with renal atherosclerotic lesions (CORAL) study’ with expected completion in the year 2010,40.Cooper C.J. Murphy T.P. Matsumoto A. et al.Stent revascularization for the prevention of cardiovascular and renal events among patients with renal artery stenosis and systolic hypertension: rationale and design of the CORAL trail.Am Heart J. 2006; 152: 59-66Abstract Full Text Full Text PDF PubMed Scopus (266) Google Scholar have to show, whether revascularization of the renal artery may improve the high cardiovascular mortality of patients with ARAS.
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