Treatment of Atherosclerotic Renal Artery Stenosis
Alberto Morganti,
Chiara Bencini,
Cecilia Del Vecchio and
Maria Strata
Cattedra di Medicina Interna and Centro Ipertensione Arteriosa, Ospedale San Paolo and Centro Fisiologia Clinica e Ipertensione, Ospedale Maggiore, University of Milan, Italy.
Correspondence to Prof. Alberto Morganti, Centro Fisiologia Clinica e Ipertensione, Ospedale Maggiore, Milano, Via F. Sforza, 35, 20122 Milano Italy. Phone: 0039-02-55033506; Fax: 0039-02-5457666;
ABSTRACT. The increasing prevalence of atherosclerotic renalartery stenosis (ARAS) has prompted in recent years a more aggressivetreatment of this condition for reducing BP and for preservingthe jeopardized renal function. Percutaneous transluminal renalangioplasty (PTRA), alone or in conjunction with stent implantation,may be useful for both these goals. However, despite the methodologicalimprovements that make this procedure much safer than surgery,caution must be applied before PTRA is extended to all patientswith ARAS. Indeed, PTRA is associated with a 23% rate of major/minorcomplications and with a 20% rate of restenosis, even in arteriesimplanted with stent. Moreover the cure rate of hypertensionachievable with PTRA is, at best, around 10%, with a 40% rateof improvements. Even for rescuing the ischemic kidney, PTRA/stentimplantation are not always effective; only 35% of patientswith ARAS have some improvement in renal function. These dataindicate that there is an urgent need of rigorous criteria forselecting among the many patients with ARAS those who may actuallybenefit from the dilation procedure. E-mail: alberto.morganti@unimi.it
Atherosclerotic renal stenosis (ARAS) is a rather frequent conditionoften but not necessarily associated with hypertension, which,because of its progressive nature, is becoming one of the leadingcauses of end-stage renal disease (ESRD). Indeed it has beenreported that ARAS progress in 51% of the cases within 5 yrand renal atrophy develops in 21% of patients in whom ARAS isinitially greater than 60% of the caliber of the vessel (1,2).According to the United States Renal Data System database, ARASaccount for up to 12 to 14% of all new patients entering a dialysisprogram each year (3). The overall annual cost for patientswith ESRD is calculated around 12 billion dollars; therefore,it is apparent that the economic burden due of this diseaseand its consequences are huge, as are the potential savingsachievable by preventing the progression of the stenosis.
The exact prevalence of ARAS in the general population is unknownbecause many cases of ARAS remain undetected. However angiographicstudies carried out in patients with coronary artery diseaseindicate a 30% prevalence of ARAS, the narrowing being greaterthan 50% in half of the cases with 4% of bilateral lesions (4).In elderly patients or in those with atherosclerotic peripheralvascular disease or malignant hypertension, the prevalence ofARAS may be even higher, approaching 50% (5), and it is likelyto increase in the future in relation to the aging of the populationand to the increasing frequency of diabetes mellitus. In thisrespect, in a recent national multicenter survey carried outin Italy, we found that among 459 hypertensive patients referredto 19 hypertension centers for the clinical suspicion of renovascularhypertension, 176 (38%) had an angiographically proven ARAS;moreover, in 76% of the cases, the ARAS was greater than 70%;in 65 patients (37%), it was bilateral (6).
These epidemiologic data underline the need for an aggressivediagnostic approach and treatment of ARAS for treatment of hypertensionand for prevention of the ischemic nephropathy. Both those goalscan be achieved, to some extent, with percutaneous transluminalrenal angioplasty (PTRA). Herein, we will briefly summarizethe most recent results obtained with this procedure in relationto its technical success and to its effects on BP and on renalfunction.
PTRA: Rate of Technical Success, Restenosis, and Complications
Despite the improvement of the devices used for PTRA, whichhas greatly increased the rate of technical success, it mustbe appreciated that a small but sizable portion of these proceduresfails. In a meta-analysis carried out in the early 1990s, Ramseyand coworkers (7) found that the overall rate of residual stenosis>50% was 12%. In another more recent review encompassinga total of 1417 angioplasties carried out in 20 experiencedcenters, the overall rate of technical failures was 30% and45% in ostial ARAS (8). In our experience gathered since 1985,20 (11%) of 197 procedures failed; moreover, another 15 procedureswere attempted but not completed because of the difficultiesin reaching the stenotic artery and/or in positioning the dilationcatheter across the ARAS (9). The introduction of stents hasgreatly increased the rate of favorable outcomes of PTRA, particularlywith respect to the most critical ARAS, the ostial and paraostial;as a result of stent use, the rate of technical success is nowclose to 100% (8). However, the improvement achieved with stentsfor preventing the restenosis has been much less dramatic dueto the persistent problem of neointimal proliferation. In Rees’review (8), the rate of restenosis observed in 563 ARAS treatedwith stent implantation was 23%, i.e., only slightly lower thanthat observed with PTRA alone. In another study, Plouin et al.(10) examined 92 patients angiographically 8 mo after a technicallysuccessful PTRA and a rate of restenosis of 19%, whereas Klowet al. (11) in a similar study found that the rate of patentrenal arteries was only 60%. In our own series, including PTRAwith and without stent implantation, the rate of restenosisobserved angiographically or with echo-Doppler during an averageof 6 mo of follow-up was 11% (9). It is likely that the relativediscrepancies between these studies are due to the extent towhich the ARAS have been initially dilated, which is known topredict the risk of restenosis (12), as well as to the differentmedical treatment used to prevent it. Finally, it is needlessto say that PTRA, although much less invasive than surgery,has its own drawbacks. In 512 PTRA with and without stent implantation,Moss (13) has found a 22.9% complication rate, some of whichare clinically relevant, such as renal hematoma and permanentreduction of renal function. In another series of 1118 PTRA,2% of patients required a reparative renal surgery, 2.2% hada renal infarct, and 1.1% had cholesterol embolization (14).In our experience, the rate of complications was 23%, with a4% rate of serious complications; that is, three cases of embolization,three renal infarcts, and one case of severe renal artery dissection(9).
Comparison of studies addressing the effects of PTRA on BP ishampered by the different criteria of selection of patients,as well as by the differences in the definition of improvementin BP, in the duration and modalities of follow-up, and in medicaltreatment. Despite these limitations, it is generally agreedthat the reduction in BP achievable with PTRA in patients withARAS is quite scarce. In Ramsey’s review (7), which reportsthe experience of ten centers with 691 patients treated withPTRA, only 19% were cured; 51% were improved, and 30% had unchangedBP. In other reviews, the effects on BP are even less encouraging;for instance, in a report by Klow et al. (11), only 8% of severalhundreds of hypertensive patients were actually cured by PTRA.In 66 patients of ours followed for at least 6 mo and in whomthe patency of the dilated artery was confirmed mostly by echo-Dopplervelocimetry, the rate of cure was only 3%, with a 38% rate ofimprovements (9). The introduction of stents has also not improvedthe outcome of PTRA on BP. Indeed, Dorros et al. (15) followedfor 4 yr 163 patients successfully treated with stent implantationand found that only one was cured and that 42% had some improvement.These negative results are not surprising if one considers thatthe great majority of patients with ARAS have been exposed tothe deleterious effects of high BP for a number of years, resultingin extensive renal and vascular damage, which prevents the returnof BP to normal levels, even after the dilatation of the stenoticartery. This conclusion obviously is not to say that PTRA isalways worthless for treating hypertension but rather to stressthe need for a careful selection of the few patients who maybenefit most from the dilatation procedures. For those patientsnot fulfilling the diagnostic criteria of real renovascularhypertension, and for those in whom even PTRA is consideredtoo risky, it should be kept in mind that the medical treatmentpermits the same degree of BP control achievable with the dilationprocedures. Indeed the three major studies that compared theeffects of PTRA and of medical treatment in patients with ARASfound that the BP reductions obtained with the two approacheswere similar, the only advantage for patients treated with PTRAbeing a diminution of the drug regimen (10,16,17).
In theory, there are several reasons to believe that PTRA shouldbe used more extensively for preserving renal function thanfor reducing BP. First, in view of the progressive nature ofARAS, the dilation should be performed before the ischemic damageof the kidney has occurred; in this respect, it has been shownthat the renal outcome of PTRA is better when the renal functionis still normal. Moreover the overall cardiovascular risk ofpatients undergoing PTRA with a baseline level of serum creatininegreater than 1.5 mg/dl is five times higher than that of patientsin whom creatinine is below that value (15). The second reasonfor using PTRA more liberally is that, so far, there are nodrugs that can positively halt the progression of ARAS. However,there is no evidence either supporting the assumption that dilationof ARAS will positively improve the renal function. In a largemeta-analysis by Middleton (18), it was found that only 25%to 53% of patients undergoing PTRA had some improvement of renalfunction. In another review of 215 patients with ARAS and mildrenal insufficiency treated with stent implantation, only 35%had some improvement in renal function as estimated by the changesin serum creatinine or creatinine clearance, whereas another35% of these patients were only stabilized by the procedure(8). A similar percentage of improvements was observed by Dorroset al. (15) during 4 yr of follow-up, whereas Watson et al.(19) found that the decline in renal function was delayed in25 of 33 stent-implanted patients. It appears that, even forpreserving renal function, patients who may actually benefitfrom dilation should be rigorously selected to the same extentas those chosen for a possible antihypertensive effect.
Unfortunately, there is no consensus on which could be a validmarker of a favorable renal outcome of PTRA (20). We have recentlyaddressed this issue by using the radioisotopic technique, whichallows an accurate evaluation of the split function of the twokidneys to eliminate the limitations inherent to creatinineand creatinine clearance. Using this methodology, we have examinedthe short- and long-term effects of PTRA/stent implantationin 21 kidneys with ARAS and found an overall improvement ofGFR in the dilated kidney of 8 ml/min (21). This increase wasbiphasic; half of it occurred with 1 wk after the procedure,and the remaining during the following 6 mo. These observations,which have also been made by other investigators (22), are ofinterest because they suggest that the preservation of the renalfunction depends not only on the restoration of renal bloodflow but also on the wearing off of other ischemia-induced mechanismsof renal damage that may require a long period of time to fullyregress (23). We also found a direct correlation between theshort- and long-term effects of PTRA on GFR of the dilated kidneyand baseline values of peripheral plasma renin activity andangiotensin II (AngII), as if the degree of activation of therenin system were a predictor of the functional recovery ofthe kidney. From a mechanistic point of view, this finding fitswell with the notion that AngII is essential for the maintenanceof GFR; indeed, if renin is released in proportion to the reductionin renal blood flow (24), it is entirely plausible that theischemic kidneys exposed to the highest concentration of AngIIare also those more suitable to increase the GFR when the renalblood flow is restored by a successful PTRA.
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Abstract
Introduction
