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Primary renal artery stenting: Characteristics and outcomes after 363 procedures
Primary renal artery stenting: Characteristics and outcomes after 363 procedures Robert J. Lederman, MD,a,b Farrell O. Mendelsohn, MD,a Renato Santos, MD,a Harry R. Phillips, MD, FACC,a Richard S. Stack, MD, FACC,a and James J. Crowley, MD, MRCPIa Durham, NC, and Ann Arbor, Mich
Background Stenting improves the acute results of percutaneous balloon angioplasty for atherosclerotic renal artery stenosis. Predictors of benefit and angiographic restenosis are not well understood. We describe the technical and clinical success of renal artery stenting in a large consecutive series of patients with hypertension or renal insufficiency. We identify clinical, procedural, and anatomic factors that might influence outcome, restenosis, and survival.
Methods Primary renal artery stenting was performed in 300 consecutive patients who underwent 363 stent procedures in 358 arteries. Angiograms were analyzed quantitatively. Clinical and angiographic follow-up data are available after a median of 16.0 months.
Results At baseline, 87% of patients had hypertension, and 37% had chronic renal insufficiency. The mean age was 70 years (interquartile range 63.1-74.6) years. The stenosis was unilateral in 49% and bilateral in 48% and involved a solitary functioning kidney in 3.6%. The stenting procedure was successful in all attempts. There were no procedural deaths or emergency renal surgical procedures. Postprocedure azotemia was seen in 45 of 363 (12%) procedures but persisted in only 6 patients (2%), all of whom had baseline renal insufficiency. Systolic and diastolic blood pressures were significantly reduced (systolic blood pressure from 164.0 ± 28.7 to 142.4 ± 19.1 mm Hg, P < .001). At follow-up, 70% of patients had improved blood pressure control regardless of renal function. In patients with baseline renal insufficiency, 19% had improvement in serum creatinine levels at follow-up, 54% had stabilization, and 27% had deterioration. Follow-up mortality was 10% and was predicted by baseline creatinine levels (odds ratio 1.72 for each 1 mg/dL creatinine increment, 95% confidence interval 1.13-2.49) and extent of coronary artery disease (odds ratio 1.66 for each diseased coronary artery, 95% confidence interval 1.03-2.67). Angiographic restenosis was found in 21% of 102 patients overall and was less common (12%) in arteries with a reference caliber >4.5 mm (P < .01 vs caliber <4.5 mm). Neither poststenotic dilation nor severity of angiographic stenosis predicted clinical outcome. Conclusions Primary renal artery stenting can be performed safely with nearly uniform technical success. The majority of patients with hypertension or renal insufficiency derive benefit. Follow-up mortality is 5-fold higher in patients with baseline renal insufficiency. Clinical and angiographic features did not predict blood pressure or renal functional outcome. Restenosis is more common in renal arteries with a reference caliber less than 4.5 mm. (Am Heart J 2001;142:314-23.)
Atherosclerotic renal artery stenosis (RAS) is associated with hypertension and progressive renal dysfunction.1 Untreated, RAS severity tends to progress2-6 and may be associated with loss of functioning renal mass. Renal revascularization is an accepted treatment for From the aDivision of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC, and the bDivision of Cardiology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Mich. Presented in part at the 48th Annual Scientific Sessions of the American College of Cardiology, New Orleans, La, March 1999. Guest Editor for this manuscript was Peter B. Berger, MD, Mayo Clinic, Rochester, Minn. Submitted July 7, 2000; accepted May 1, 2001. Reprint requests: Robert J. Lederman, MD, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Dr, Room B1 D219, Bethesda, MD 20892. E-mail: [email protected] Copyright © 2001 by Mosby, Inc. 0002-8703/2001/$35.00 + 0 4/1/116958 doi:10.1067/mhj.2001.116958
patients with advanced renovascular disease associated with drug-refractory hypertension or recurrent pulmonary edema.7,8 Surgical reconstruction or bypass is effective but limited by procedural morbidity and mortality.9,10 Catheter-based treatment is an attractive alternative that may be tolerated by a greater proportion of affected patients. However, balloon angioplasty has a high incidence of technical failure because aorto-ostial plaques tend to recoil or leave bulky dissections.11,12 Endoluminal stents provide better angiographic and hemodynamic results than does angioplasty alone.13-16 We report a series of patients with uncontrolled hypertension or chronic renal failure along with renal artery stenosis detected for the most part during angiography for coronary artery disease. We hypothesize that renal artery stenting is safe and associated with improved blood pressure control and stabilization of renal function. In a subset of patients we also tested the
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Figure 1
Quantitative renal angiography definitions. MLD, Minimum lumen diameter.
hypothesis that angiographic restenosis is more likely in smaller-caliber renal arteries.
Transstenotic pressure gradients were not routinely measured in our laboratory to avoid catheter-induced atheroembolism.
Methods
Technique of renal artery stenting
Between June 1993 and February 1998, 361 patients underwent 436 percutaneous renal artery interventions at our institution. Sixty-one underwent balloon angioplasty alone for fibromuscular dysplasia (12 patients), atherosclerosis (0 patients), and in-stent restenosis (9 patients). The remaining 300 are described in detail here, having undergone 363 consecutive primary renal artery stent procedures involving 357 arteries. Data were collected prospectively beginning in 1996 for two thirds of the patients and retrospectively for the others.
Renal artery interventions were performed with techniques adapted from coronary stenting, in separate sessions from coronary procedures. Renal ostia typically were engaged via a femoral artery with an 8F Renal Double Curve-1 guiding catheter (Cordis, Miami, Fla). Selective angiography was performed in 2 oblique views. Heparin was administered to achieve an activated clotting time between 250 and 300 seconds. Stenoses were crossed with 0.018-inch steerable guidewires. When the vessel reference caliber exceeded 6.0 mm (the largest 0.018-inch-compatible balloon currently available), a catheter was used to exchange for a high-support 0.035-inch Rosen guidewire. Lesions were predilated and then nonarticulated medium Palmaz stents were hand crimped on the same balloon. The guiding catheter was advanced across the lesion to protect the baremounted stent from dislodgement during delivery. We took care to deploy the stent across a full thickness of aortic wall in ostial lesions, to protrude 1 to 2 mm into the aortic lumen, and to anticipate stent shortening at higher diameters. All stents were postdilated at pressures exceeding 10 atm with noncompliant balloons sized between the reference caliber and the maximal (poststenotic) vessel caliber. Sheaths were removed as soon as the activated clotting time fell below 150 seconds. Patients were treated with aspirin 325 mg daily indefinitely and ticlopidine 250 mg twice daily for 2 to 4 weeks.
Definitions and coding Baseline blood pressures were captured from the lowest measurement before procedural sedation. Inpatient and clinic measurements were used in place of catheterization suite measurements, when available. Antihypertensive medications prescribed by the primary care physician was tabulated for each patient. Multiple concurrent diuretics were coded as a single agent. Multiple agents of a single class (eg, β-adrenergic antagonists, angiotensin-converting enzyme [ACE] inhibitors) generally were coded as one agent unless they have recognized clinical utility in combination (eg, calcium channel antagonists). Hypertension was defined as systolic blood pressure (BP) exceeding 140 mm Hg or diastolic BP exceeding 90 mm Hg in multiple measurements. Malignant hypertension (MHTN) was defined as hypertension associated with life-threatening pulmonary edema, encephalopathy, or rest angina related to hypertension. Chronic renal insufficiency (CRI) was a baseline creatinine level exceeding 1.4 mg/dL. Acute renal injury particularly after exposure to intravascular contrast or ACE inhibitors did not qualify as CRI. A renal artery lesion was considered for stenting if the visually estimated diameter stenosis exceeded 70% in a patient with renal insufficiency or uncontrolled hypertension.
Quantitative angiography Quantitative arteriographic analysis was performed off-line by experienced technicians unfamiliar with the clinical outcomes with use of digital calipers calibrated against contrastfilled catheters. Two segments were measured for reference vessel caliber, both the “most-proximal normal-appearing” segments beyond proximal stenoses and a distal reference point, at which the arterial walls become parallel before the primary bifurcation (Figure 1). Lesion length was measured
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Table I. Baseline demographic characteristics for 300 patients undergoing PTRAS Age (y) 70.0 (63.1-64.6) Female sex 48.0% Duration of coronary artery disease (y) 3.89 (0.67-8.4) Extent of coronary artery disease by angiography Insignificant 18.5% 1-vessel 23.1% 2-vessel 18.5% 3-vessel 39.9% Ejection fraction 53.0% (43.0-62.0) Congestive heart failure symptoms 30.3% Diabetes mellitus 29.1% Tobacco 31.2% Hyperlipidemia 69.6% Bilateral stenosis or stenosis of solitary 41.3% patent artery Indications for PTRAS (not mutually exclusive) Hypertension 87% MHTN 13% CRI 37% Hypertension and CRI 25.3% Data are expressed as percent of total or as median (interquartile range).
between seemingly normal artery segments or extending to the ostium. The degree of poststenotic dilation was reported as the maximum caliber of the artery in this segment, unless the poststenotic segment extended beyond a major bifurcation. Poststenotic dilation was present if the caliber ratio of the poststenotic segment to the most proximal normal reference exceeded 1.2. The aortorenal angle was defined as the entry angle of the renal artery with the infrarenal aorta. Bilateral RAS was considered present if the major contralateral renal artery had an angiographic diameter stenosis >50%. Angiographic restenosis was present if diameter stenosis exceeded 50% of the proximal reference diameter on follow-up angiography.
Follow-up data collection and categorical clinical outcomes Follow-up data were collected from hospital, clinic, and primary physician records and from direct telephone inquiries with patients. Follow-up BP used both oscillometric and manual measurements. Follow-up BP is reported as the average of the 3 most recent BP recordings available after the procedure. Blood pressure improvement was defined as reduction of systolic blood pressure by at least 20 mm Hg. Late renal deterioration was defined as a rise in the serum creatinine level by at least 0.4 mg/dL to more than 1.4 mg/dL at follow-up. Late renal improvement was defined as a fall in serum creatinine by at least 0.4 mg/dL at follow-up. Transient postprocedural azotemia was defined as an acute creatinine increment exceeding 0.4 mg/dL to above 1.4 mg/dL and resolving within 30 days; otherwise it was considered sustained. Restenosis data were gathered from clinically driven angiography performed as part of peripheral and cardiac catheterization procedures.
Table II. Lesion characteristics No. of procedures Lesion type De novo stenosis Restenosis after previous angioplasty Restenosis after previous stent Aortorenal graft anastomosis Lesion location Ostial Nonostial Lesion appearance Atherosclerotic Fibromuscular dysplasia
363 94.5% 3.6% 1.4% 0.5% 95.3% 4.7% 97.8% 2.2%
Statistical analysis Clinical outcomes were analyzed on a per-patient basis. Procedural and angiographic outcomes, however, were analyzed on a per-procedure basis. Statistical analyses were performed with SPSS for Windows version 8.0 (SPSS, Chicago, Ill) by one author (R. J. L.). All tests were 2 tailed. Paired-sample t tests describe the influence of the percutaneous renal artery stent procedure (PTRAS) on clinical parameters. The influence of baseline variables on categorical outcomes was tested by independentsample t test or Mann-Whitney U test as appropriate. Independent predictors of mortality were identified by a Cox proportional hazards model, after adjustment for follow-up interval. Creatinine was logarithm-transformed for multivariate modeling, although for the sake of clinical utility odds ratios are reported only for creatinine itself.
Results Patient and vessel characteristics Baseline clinical characteristics are described in Table I. Patients were generally referred for renovascular intervention for poorly controlled hypertension requiring 2 or more medications (87%) or for renal dysfunction (37%). Only 13% had MHTN. Data regarding duration of hypertension were not captured. Lesion characteristics are described in Table II. Table III shows quantitative angiographic analysis performed on 334 (92%) available films. Poststenotic dilation was present in 45% of treated vessels. In spite of a wide variation of aortorenal angle, all lesions were treated through a transfemoral approach. Vital status was obtained for all 300 patients. Detailed clinical follow-up information was available for 267 patients (89%) after a median of 16.0 months (interquartile range 6.4-23.5) after PTRAS.
Acute outcomes and complications The PTRAS procedure was successful in all 363 lesions attempted in all patients. Palmaz medium stents (Cordis) were used in all but 2 procedures. A single 15mm P154 stent was deployed in 68.3% of patients. Two stents were deployed in 7.4% of procedures, typically
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Figure 2
Clinical outcome in subsets of patients with hypertension (HTN), CRI, or both.
to cover a distal stent-margin dissection. The largest postdilatation balloon had a mean nominal size of 6.1 ± 0.9 mm and a mean maximum inflation pressure of 12.0 ± 3.0 mm Hg. Procedural complications occurred in 6 patients. One patient died of myocardial infarction not attributable to the PTRAS procedure. He had inoperable multivessel coronary artery disease (CAD), recurrent myocardial infarction, severe hypertension, and bilateral RAS complicated by pulmonary edema requiring mechanical ventilation. Despite a technically successful PTRAS procedure, he had recurrent myocardial infarction and additional support was withdrawn after 3 days. One patient had intraprocedural thrombosis of the target renal artery. She had multiple medical problems including a baseline creatinine level of 3.7 mg/dL and a history of heparininduced thrombocytopenia with thrombosis. Anticoagulation was performed with a heparinoid but nevertheless a nonocclusive arteriographic filling defect developed after balloon predilatation, which persisted after stent placement. Intra-arterial tissue plasminogen activator infusion resolved the thrombus but renal function continued to deteriorate and the patient required hemodialysis 6 months afterward. In another patient, a partially expanded stent migrated into the aorta during deployment. It was retrieved with a balloon and deployed uneventfully in the right common iliac artery. Adjunctive abciximab was used in 3 patients. One had a nonocclusive guidewire-induced dissection of a first-order renal artery branch, which was normal on follow-up angiography 4 weeks later. Another had a hazy-appearing vessel despite stenting. Another had hypersensitivity to aspirin and received abciximab
Table III. Quantitative vessel characteristics Preprocedure Preprocedure Minimum lumen diameter (mm) Proximal reference (mm) Stenosis severity by proximal reference (%) Distal reference (mm) Stenosis severity by distal reference (%) Poststenotic dilation ratio Poststenotic dilation >20% (%) Lesion length (mm) Aortorenal angle (degrees)
Postprocedure
Mean
SD
Mean
SD
2.06
0.86
6.11
1.12
5.45 62.2
1.38 15.6
5.58 –9.7
5.08 59.3
1.31 5.18 15.1 –18.0
1.23 44.8
0.23
6.71 77
3.68 21
1.3 34.7 1.31 23.8
Quantitative off-line angiographic analysis was performed on 334 available films of 363 procedures. Definitions are listed in the Methods section. Measurement points are depicted in Figure 1.
and ticlopidine during an otherwise uneventful procedure.
BP response Systolic and diastolic BPs were significantly reduced (systolic BP from 164.0 ± 28.7 to 142.4 ± 19.1 mm Hg, P < .001) , regardless of whether PTRAS was indicated for hypertension or CRI (Table IV). Blood pressure control improved in 70% of patients. At follow-up 72 patients (34%) with hypertension used
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Figure 3
Table IV. BP and creatinine before PTRAS and after late follow-up Baseline
Serum creatinine (Cr) changes in all patients and overlapping clinical subsets with hypertension, baseline renal insufficiency, and normal renal function.
fewer antihypertensives, 83 (39%) used the same number, and 57 (27%) used more. All 3 groups of patients had equivalent frequency of blood pressure improvement. Only 2 patients with atherosclerotic RAS had normal blood pressure after withdrawal of all antihypertensive medications at follow-up. Neither clinical, procedural, nor anatomic features (recorded in the tables) at baseline predicted a favorable BP response to PTRAS. In particular, patients with poststenotic renal artery dilation were no more likely to have improved blood pressure after PTRAS than those without. Clinical response was not related to minimum lumen diameter or to percent stenosis severity. Moreover, patients with “global” RAS (involving all patent renal vessels) were no more likely in our series to derive BP benefit than those with unilateral disease.
Renal function Renal parenchymal disease was common in our patient population. CRI was present in 101 (37%) at baseline and in 142 (47%) at follow-up at a “liberal” threshold of 1.4 mg/dL. Late renal deterioration was predicted by baseline renal insufficiency (56.7% vs 23.8%, P < .01), previous MHTN (33.3% vs 11.9%, P = .05), and history of congestive heart failure (CHF) (43.3% vs 25.3%, P = .03). The long-term renal outcome of patients undergoing PTRAS is schematized in Figure 2. From the whole group serum creatinine fell significantly (>0.4 mg/dL) in 7.5%, showed no change in 78.1%, and rose in 14.4% of patients at follow-up. Among patients with renal insufficiency at baseline, 19.1% had a significant drop in creatinine at follow-up, although another 26.6% had a late creatinine rise. Pa-
All patients (n = 265) Systolic BP Diastolic BP Creatinine Antihypertensives PTRAS for hypertension (n = 227) Systolic BP Diastolic BP Creatinine Antihypertensives PTRAS for CRI (n = 94) Systolic BP Diastolic BP Creatinine Antihypertensives
Follow-up
P value
164.0 ± 28.7 142.4 ± 19.1 83.9 ± 13.7 75.7 ± 10.8 1.49 ± 0.79 1.60 ± 0.97 2.5 2.5
<.001 <.001 .052
164.7 ± 27.4 142.8 ± 18.6 84.3 ± 13.7 76.1 ± 10.9 1.37 ± 0.66 1.50 ± 0.94 2.5 2.5
<.001 .079 <.001
163.0 ± 29.1 142.6 ± 19.5 83.0 ± 12.9 74.1 ± 11.2 2.22 ± 0.90 2.34 ± 1.21 2.9 2.8
<.001 .445 <.001
Data sets are not mutually exclusive.
tients having baseline renal insufficiency constituted two thirds of patients who had a late renal deterioration. Only 7.7% of patients with normal baseline renal function had a late creatinine rise. Findings were similar when different categorization criteria were applied (20% creatinine change when serum creatinine exceeded 1.4 mg/dL). Neither clinical, procedural, nor anatomic features otherwise predict renal functional outcome. Transient postprocedural azotemia was found in 39 patients during 45 procedures. Transient azotemia was more common in patients with (22.5%) than without (4.2%) baseline CRI. Azotemia persisted (more than 1 month) in 6 patients, all of whom had baseline renal insufficiency (5.4% of patients with CRI, 2% of all patients). Overall, the majority of patients undergoing PTRAS had either a significant BP improvement or long-term stabilization of renal function (Figure 3). This was true whether they had baseline hypertension, renal insufficiency, or both. Only 3 patients had a late deterioration of renal function without significant BP improvement after PTRAS.
Malignant hypertension MHTN was the primary indication for PTRAS in 39 patients. Presenting symptoms included pulmonary edema in 25 (64%), encephalopathy in 7 (18%), and severe angina resulting from uncontrolled hypertension in 7 (18%). Compared with patients treated for benign hypertension, patients with MHTN had higher initial systolic BP (175 ± 26 vs 161 ± 27 mm Hg, P < .01), used more antihypertensive medications (3.2 ± 1.2 vs 2.3 ± 1.2, P < .01), had more frequent CRI (56% vs 24%, P < .001), and diabetes mellitus (44% vs 27%, P =
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Table V. Univariate predictors of angiographic restenosis Characteristic
No restenosis
Figure 4
P Restenosis value
No. 79 23 Procedural Balloon diameter (mm) 6.14 ± 0.73 5.38 ± 0.94 <.01 Balloon maximum 11.53 ± 3.34 11.72 ± 2.76 .82 pressure (atm) No. of stents placed 1.00 ± 0.31 1.00 ± 0.32 1.00 Total length of stents 17.24 ± 4.41 16.58 ± 4.10 .55 placed Lesion MLD preprocedure (mm) 2.04 ± 0.87 1.89 ± 0.66 .51 Lesion length (mm) 6.75 ± 3.35 7.39 ± 3.18 .47 Proximal reference 5.59 ± 1.22 4.73 ± 1.11 .01 vessel segment (mm) Minimum lumen diameter 6.06 ± 0.95 5.27 ± 0.90 <.01 poststent (mm) Poststenosis dilation 6.79 ± 1.31 5.54 ± 1.27 <.01 caliber (mm) Bilateral or solitary 58 (69.9%) 12 (60.0%) .4 RAS Follow-up angiography information was available for 102 patients.
.03), higher baseline creatinine (2.0 ± 1.1 vs 1.3 ± 0.5 mg/dL, P < .01), more extensive coronary artery disease (2.3 ± 1.1 vs 1.7 ± 1.2 vessels, P = .01), more frequent left ventricular systolic dysfunction (36.1% vs 18.4%, P = .021), and more frequent (71.1% vs 21.3%, P < .01) and severe (New York Heart Association class 3.5 ± 1.3 vs 2.8 ± 1.0, P = .03) CHF symptoms. At follow-up BP control improved to a similar extent in patients with MHTN as in those with benign hypertension, although the magnitude of BP lowering was greater. Although most patients showed long-term stabilization of renal function, there was a trend toward a worse outcome in the MHTN group (20.0% deterioration of creatinine vs 6.3%, P = .06). Mortality after 16 months was higher in patients with MHTN (23% vs 6.3%, P < .01).
Restenosis Follow-up angiography was available in 102 patients (34%) after an average of 303 days. Angiographic restenosis was found in 23 patients (21.3%). When restenosis was clinically suspected (in 26 patients), it was detected in 11 (42%) an average of 343 days after intervention. Incidental angiography detected restenosis less frequently (9 patients, 12%). No baseline clinical markers predicted restenosis. Restenosis tended to be more common among patients who had late renal functional deterioration or lack of BP improvement (61.1% vs 39.2%, P = .09). In contrast, markers of large arteries (reference vessel size, caliber of poststenotic segment, and minimum lumen diameter after stenting) were associated with a
Restenosis incidence after PTRAS according to reference vessel diameter.
significantly lower incidence of angiographic restenosis (Table V). The restenosis rate was 36.0% for vessels with a reference diameter <4.5 mm compared with 15.8% in vessels with reference diameter 4.5 to 6.0 mm (P = .068 compared with smallest vessels) and 6.5% in vessels with reference diameter exceeding 6.0 mm (P < .01 compared with smallest vessels) (Figure 4).
Mortality Vital status was determined for all 300 patients. Thirty (10%) died during the 16-month follow-up period. Mortality was higher in patients with baseline CRI (19.1% vs 4.3%, P < .001); these patients constituted 70% of all deaths. Other univariate predictors of death (Table VI) included serum creatinine, MHTN, CHF, left ventricular dysfunction, number of diseased coronary arteries, and significant stenosis of all remaining renal arteries (“global” RAS). Multivariate regression identified baseline creatinine (odds ratio 1.72 for each 1-mg/dL creatinine increment, 95% confidence interval 1.13-2.49) and extent of coronary artery disease (odds ratio 1.66 for each diseased epicardial coronary artery, 95% confidence interval 1.03-2.67) as independent predictors of mortality.
Discussion This is the largest published single-center series of PTRAS. PTRAS was safe and was performed with high technical success. The majority of patients with RAS and hypertension or renal insufficiency seemed to derive clinical benefit.
Limitations This study is limited by the absence of a control group of patients treated pharmacologically, by concur-
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Table VI. Predictors of death during follow-up
Characteristic Age (y)* Female sex CRI Creatinine† MHTN Systolic BP Diastolic BP Ejection fraction <0.45 No. of CAD vessels CHF Diabetes mellitus Tobacco history Hyperlipidemia “Global” RAS
Alive at follow-up (n = 270)
Dead at follow-up (n = 30)
67.9 ± 9.4 132 (48.9%) 90 (33.3%) 1.4 ± 0.7 30 (11.1%) 162.8 ± 28.8 83.5 ± 13.8 43 (22.9%) 1.7 ± 1.2 69 (26.8%) 75 (27.8%) 185 (68.8%) 181 (67.3%) 106 (39.3%)
70.2 ± 7.2 12 (40.0%) 21 (70.0%) 2.0 ± 1.0 9 (30.0%) 167.5 ± 25.9 83.8 ± 12.3 12 (44.4%) 2.4 ± 1.0 18 (60.0%) 12 (40.0%) 23 (76.7%) 15 (50.0%) 18 (60.0%)
Univariate P value .210 .360 <.001 <.001 .038 .386 .885 .043 .003 .001 .211 .351 .084 .029
Multivariate P value NS NS — .004 NS — — NS .039 NS — — NS NS
OR (95% CI)
1.72 (1.13-2.49)
1.66 (1.03-2.67)
OR, Odds ratio; CI, confidence interval; NS, not significant. *Categorical age > median in Cox regression analysis. †Log-transformed for Cox regression analysis, data are reported for untransformed creatinine.
rent pharmacotherapy that has an impact on both BP and glomerular filtration rate, by retrospective data collection, by heterogeneous follow-up of BP and creatinine data at variable time points and at multiple sites, and by nonsystematic follow-up angiography. In particular, BP recordings were extracted from charts. Manual sphygmomanometry has been shown to exaggerate the blood pressure–lowering effect of renal artery angioplasty compared with automated oscillometric and ambulatory BP measurements.17
Efficacy PTRAS lowered systolic and diastolic BPs in >70% of our patients after a 16-month mean follow-up, to a range shown desirable in large contemporary clinical trials.18-20 BP lowering was equivalent in patients with normal and abnormal renal function. In contrast to other published series of PTRAS for atherosclerotic RAS,14,21-23 only 2 patients in our mostly elderly population were “cured” of hypertension. Undoubtedly the majority of our patients had concurrent essential hypertension or parenchymal renal disease.24 Overall, patients used the same mean number of antihypertensive medications at follow-up, although 27% used more antihypertensive medications than they had previously. This probably reflects the intensified medical therapy and risk factor reduction patients often undertake after identification of significant coronary and peripheral artery disease. In our patients the average serum creatinine level, an estimate of glomerular filtration rate,25 tended to increase during follow-up (1.49 ± 0.79 vs 1.60 ± 0.97 mg/dL, P = .05). This may reflect either the natural history of renal insufficiency or procedural renal injury. A
transient creatinine increase, presumably related to contrast nephrotoxicity or renal atheroembolism, was seen in 13% of our patients and was more common in those with pre-existing renal failure (22.5%) than without (4.2%). Creatinine returned to normal in almost all patients within 30 days. Sustained azotemia was detected in only 2% of patients after the first month. Even after relief of renal artery obstruction, many of our patients had additional renal comorbidity, including irreversible parenchymal injury, diabetic glomerulopathy, subclinical atheroembolism, and essential hypertension. In some patients correction of RAS by stenting might be expected to delay or halt the decline in renal function by improving renal blood flow and blood pressure control. Indeed, there is evidence that percutaneous26,27 and surgical renal revascularization28,29 reduce the rate of renal functional deterioration despite a continued rise in serum creatinine. We do not know the magnitude or tempo of renal functional deterioration had our patients not undergone PTRAS. Ultimately this question can be answered only in a randomized comparison of invasive and medical therapy. Nineteen percent of patients in this series with baseline CRI had significant improvement in glomerular filtration. We were careful not to misclassify patients recovering from acute renal (ie, contrast) injury as having baseline CRI. Finally, we found no clinical, angiographic, or procedural markers that helped predict clinical improvement in BP or renal insufficiency after the procedure. Patients treated for bilateral or global RAS were not more likely to derive improved BP control than patients treated for unilateral RAS, in contrast to other reports.30 This finding is tempered, however, by the high inci-
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dence of “incompletely revascularized” bilateral RAS. Angiographically more severe stenoses were not associated with better clinical outcome than less severe stenoses among patients selected for intervention. Finally, poststenotic dilation, considered a marker of chronic hemodynamically significant flow perturbation, did not predict improved BP response, in contrast to other reports.31
Quantitative renal angiography and the results of stenting There are no uniform standards for quantitative interpretation of renal angiograms. Normal main renal arteries have a fusiform proximal segment and taper distally before the primary branch (Figure 1). Choosing a “normal” renal artery reference segment poses a challenge analogous to that in carotid atherosclerosis, in which plaque involves a bifurcation and a dilated carotid bulb. In the North American Symptomatic Carotid Endarterectomy Trial (NASCET),32 the reference caliber was chosen as the first downstream internal carotid segment to have parallel arterial walls, analogous to our “most distal normal” reference. In renal arteries the distal reference may be more physiologically significant because it represents the narrowest segment of “normal” artery before it bifurcates. In this study quantitative mean stenosis severity was 61.4% with use of a distal reference site compared with 70% when the widest portion of the artery was used. Most studies, however, use the latter strategy. Both measurements suggest a qualitative exaggeration of stenosis severity by the angiographer, a well-recognized phenomenon in coronary angiography.33 The presence of post-stenotic dilation (44% in this study) further complicates quantitative analysis and also may present a technical challenge to optimizing the size of the endoluminal stent. In our laboratory proximal and ostial stenosis are treated with the proximal stent extending 1 to 2 mm into the aortic lumen and the distal stent ending within the “shoulder” segment of the poststenotic or fusiform segment of the main renal artery.
Restenosis Follow-up angiography was performed nonsystematically in 102 (34%) patients, generally as part of coronary or other peripheral artery angiographic procedures. Binary angiographic restenosis was found in 21.3%. In only half of these patients, restenosis had been suspected clinically. These restenosis rates are comparable to those of other reported series.14-16 This is the first report associating renal artery restenosis with progressively smaller reference vessel caliber. We found a high incidence of in-stent renal artery restenosis (36%) in the tercile of patients having small vessels <4.5 mm in diameter compared with larger vessels (12%). Aortorenal atherosclerotic plaques, which are sub-
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stantially bulkier than coronary artery plaques, apparently respond differently to stenting. Angiographic coronary restenosis is only 16% after stenting arteries having a mean 3.0-mm reference caliber.34 However, balloon angioplasty without stenting has an even higher incidence of technical failure and restenosis (50%-80%) in these aorto-ostial lesions.11,12 On the basis of our observation, renal arteries having a reference caliber ≤4.5 mm are less attractive targets for percutaneous therapy and consideration should be given to medical or surgical management. Conversely, renal arteries larger than 4.5 mm have an acceptably low incidence of angiographic restenosis.
Mortality There was a relatively high mortality of 10% after 16 months of follow-up. Baseline creatinine and extent of CAD were independent predictors of mortality reflecting the severity of diffuse atherosclerosis in this population. Previous studies have demonstrated that the presence of significant RAS is an independent predictor of CAD and mortality.35,36
Complications Early experiences with PTRAS reported a worrisome incidence of major complications including renal artery rupture, perforation, thrombosis, renal and systemic atheroembolism, infection, procedural technical failure, major hemorrhage, and death.21,23,26,37-42 A noteworthy feature of our experience is the uniform technical success rate and high procedural safety. In our series there were no renal artery perforations or ruptures requiring emergency surgical renal salvage. The only periprocedural arterial thrombosis occurred in a woman with known heparin-associated thrombocytopenia-thrombosis despite heparinoid anticoagulation. Transient azotemia was common in patients with baseline renal insufficiency, but sustained renal injury was infrequent (2.0% of patients overall). The appreciably lower incidence of complications in recent reports14-16,22 may reflect the translation of meticulous coronary stenting technique to noncoronary territories. This includes scrupulous anticoagulation, use of soft steerable guidewires, careful device sizing using quantitative angiography, low-pressure predilatation before stent deployment, stent deployment with the guiding catheter as delivery sheath, and high-pressure stent postdilatation taking care not to traumatize the distal vessel with the balloon. By comparison, surgical revascularization, although effective, confers a comparatively higher risk of procedural morbidity and mortality.9,10,43-46
Conclusions In experienced hands PTRAS can be performed with a high degree of technical success at low risk to the
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patient. In arteries having a reference caliber greater than 4.5 mm, angiographic restenosis is unusual. PTRAS may therefore be the treatment of choice for selected patients with significant atherosclerotic RAS. Although the majority of patients derived clinical benefit, a randomized comparison is warranted between aggressive pharmacologic and interventional therapy. We thank Mark Urtz and Thomas Hoffman for quantitative arteriographic measurements; Laura Gaulden, Patty Hoffman, and Sara and Jan Wellendorff for telephone follow-up; David Bruckman for review of statistical procedures; Hugh Wells and Laura Waugh for data entry; and Joseph Greenfield and Eric Bates for their invaluable critical review.
References 1. Novick A, Scoble J, Hamilton G. Renal vascular disease. London: WB Saunders; 1996. 2. Wollenweber J, Sheps SG, Davis GD. Clinical course of atherosclerotic renovascular disease. Am J Cardiol 1968;21:60-71. 3. Dean RH, Kieffer RW, Smith BM, et al. Renovascular hypertension: anatomic and renal function changes during drug therapy. Arch Surg 1981;116:1408-15. 4. Crowley J, Santos R, Peter R, et al. Progression of renal artery stenosis in patients undergoing cardiac catheterization. Am Heart J 1998;136:918-8. 5. Caps MT, Perissinotto C, Zierler RE, et al. Prospective study of atherosclerotic disease progression in the renal artery. Circulation 1998;98:2866-72. 6. Caps MT, Zierler RE, Polissar NL, et al. Risk of atrophy in kidneys with atherosclerotic renal artery stenosis. Kidney Int 1998;53:73542. 7. Messina LM, Zelenock GB, Yao KA, et al. Renal revascularization for recurrent pulmonary edema in patients with poorly controlled hypertension and renal insufficiency: a distinct subgroup of patients with arteriosclerotic renal artery occlusive disease. J Vasc Surg 1992;15:73-82. 8. Pickering TG, Herman L, Devereux RB, et al. Recurrent pulmonary oedema in hypertension due to bilateral renal artery stenosis: treatment by angioplasty or surgical revascularisation. Lancet 1988;2:551-2. 9. Stanley JC. The evolution of surgery for renovascular occlusive disease. Cardiovasc Surg 1994;2:195-202. 10. Cambria RP, Brewster DC, L’Italien GJ, et al. The durability of different reconstructive techniques for atherosclerotic renal artery disease. J Vasc Surg 1994;20:76-87. 11. Bonelli FS, McKusick MA, Textor SC, et al. Renal artery angioplasty: technical results and clinical outcome in 320 patients Mayo. Clin Proc 1995;70:1041-52. 12. Sos TA, Pickering TG, Sniderman K, et al. Percutaneous transluminal renal angioplasty in renovascular hypertension due to atheroma or fibromuscular dysplasia. N Engl J Med 1983;309:274-9. 13. Dorros G, Prince C, Mathiak L. Stenting of a renal artery stenosis achieves better relief of the obstructive lesion than balloon angioplasty. Cathet Cardiovasc Diagn 1993;29:191-8. 14. Blum U, Krumme B, Flugel P, et al. Treatment of ostial renal-artery stenoses with vascular endoprostheses after unsuccessful balloon angioplasty. N Engl J Med 1997;336:459-65.
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15. Dorros G, Jaff M, Mathiak L, et al. Four-year follow-up of PalmazSchatz stent revascularization for atherosclerotic renal artery stenosis. Circulation 1998;98:642-7. 16. White CJ, Ramee SR, Collins TJ, et al. Renal artery stent placement: utility in lesions difficult to treat with balloon angioplasty. J Am Coll Cardiol 1997;30:1445-50. 17. Plouin PF, Chatellier G, Darne B, et al. Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis: a randomized trial. Essai Multicentrique Medicaments vs Angioplastie (EMMA) Study Group. Hypertension 1998;31:823-9. 18. Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998; 351:1755-62. 19. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991;265:3255-64. 20. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997;157:2413-46. 21. Boisclair C, Therasse E, Oliva VL, et al. Treatment of renal angioplasty failure by percutaneous renal artery stenting with Palmaz stents: midterm technical and clinical results. AJR Am J Roentgenol 1997;168:245-51. 22. Henry M, Amor M, Henry I, et al. Renal arterial stenting: a 7 year single center experience with a series of 206 stented arteries [abstract]. J Am Coll Cardiol 1998;31(2 Suppl A):453A. 23. Thorpe A, Moss J, Harden P, et al. Renal artery stenting: a 6-year single-center experience with a series of 151 arteries with stents. J Vasc Intervent Radiol 1997;8(2 Suppl):246. 24. Streeten DH, Anderson GH Jr, Wagner S. Effect of age on response of secondary hypertension to specific treatment. Am J Hypertens 1990;3:360-5. 25. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461-70. 26. Harden PN, MacLeod MJ, Rodger RS, et al. Effect of renal-artery stenting on progression of renovascular renal failure Lancet 1997; 349:1133-6. 27. Ahuja R, Poler S, Rocha-Singh K. Palmaz stenting reverses progressive renal dysfunction in patients with global renal ischemia due to atherosclerotic renal artery stenosis [abstract]. J Am Coll Cardiol 1999;33(A Suppl):42A. 28. Dean RH, Tribble RW, Hansen KJ, et al. Evolution of renal insufficiency in ischemic nephropathy. Ann Surg 1991;213:446-56. 29. van Rooden CJ, van Bockel JH, De Backer GG, et al. Long-term outcome of surgical revascularization in ischemic nephropathy: normalization of average decline in renal function. J Vasc Surg 1999;29: 1037-49. 30. Rocha-Singh KJ, Mishkel GJ, Katholi RE, et al. Clinical predictors of improved long-term blood pressure control after successful stenting of hypertensive patients with obstructive renal artery atherosclerosis. Catheter Cardiovasc Interv 1999;47:167-72. 31. Prince MR, Schoenberg SO, Ward JS, et al. Hemodynamically significant atherosclerotic renal artery stenosis: MR angiographic features. Radiology 1997;205:128-36. 32. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis: North American Symptomatic
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33.
34.
35. 36. 37.
38.
39.
Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991; 325:445-53. Beauman GJ, Vogel RA. Accuracy of individual and panel visual interpretations of coronary arteriograms: implications for clinical decisions. J Am Coll Cardiol 1990;16:108-13. Serruys PW, van Hout B, Bonnier H, et al. Randomised comparison of implantation of heparin-coated stents with balloon angioplasty in selected patients with coronary artery disease (Benestent II). Lancet 1998;352:673-81. Valentine RJ, Clagett GP, Miller GL, et al. The coronary risk of unsuspected renal artery stenosis. J Vasc Surg 1993;18:433-40. Conlon PJ, Athirakul K, Kovalik E, et al. Survival in renal vascular disease. J Am Soc Nephrol 1998;9:252-6. Iannone LA, Underwood PL, Nath A, et al. Effect of primary balloon expandable renal artery stents on long-term patency, renal function, and blood pressure in hypertensive and renal insufficient patients with renal artery stenosis. Cathet Cardiovasc Diagn 1996;37:243-50. van de Ven PJ, Beutler JJ, Kaatee R, et al. Transluminal vascular stent for ostial atherosclerotic renal artery stenosis. Lancet 1995; 346:672-4. MacLeod MJ, Connell JM, Harden PN, et al. Transluminal vascular stents for ostial atherosclerotic renal artery stenosis. Lancet 1995; 346:1109-10.
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40. Trost D, Sos T, Jagust M, et al. Palmaz stents to treat ostial renal artery stenoses in persons with hypertension and azotemia: immediate and intermediate results. J Vasc Intervent Radiol 1997;8(2 Suppl):245. 41. Rundback JH, Gray RJ, Rozenblit G, et al. Renal artery stent placement for the management of ischemic nephropathy. J Vasc Interv Radiol 1998;9:413-20. 42. Deitch J, Hansen K, Regan J, et al. Infected renal artery pseudoaneurysm and mycotic aortic aneurysm after percutaneous transluminal renal artery angioplasty and stent placement in a patient with a solitary kidney. J Vasc Surg 1998;28:340-4. 43. Novick AC, Ziegelbaum M, Vidt DG, et al. Trends in surgical revascularization for renal artery disease: ten years’ experience. JAMA 1987;257:498-501. 44. Bergan JJ, Wilson SE, Wolf G, et al. Unexpected, late cardiovascular effects of surgery for peripheral artery disease: Veterans Affairs Cooperative Study 199. Arch Surg 1992;127:1119-23. 45. Hansen KJ, Starr SM, Sands RE, et al. Contemporary surgical management of renovascular disease. J Vasc Surg 1992;16:319-30. 46. Weibull H, Bergqvist D, Bergentz SE, et al. Percutaneous transluminal renal angioplasty versus surgical reconstruction of atherosclerotic renal artery stenosis: a prospective randomized study. J Vasc Surg 1993;18:841-50.
Background Stenting improves the acute results of percutaneous balloon angioplasty for atherosclerotic renal artery stenosis. Predictors of benefit and angiographic restenosis are not well understood. We describe the technical and clinical success of renal artery stenting in a large consecutive series of patients with hypertension or renal insufficiency. We identify clinical, procedural, and anatomic factors that might influence outcome, restenosis, and survival.
Methods Primary renal artery stenting was performed in 300 consecutive patients who underwent 363 stent procedures in 358 arteries. Angiograms were analyzed quantitatively. Clinical and angiographic follow-up data are available after a median of 16.0 months.
Results At baseline, 87% of patients had hypertension, and 37% had chronic renal insufficiency. The mean age was 70 years (interquartile range 63.1-74.6) years. The stenosis was unilateral in 49% and bilateral in 48% and involved a solitary functioning kidney in 3.6%. The stenting procedure was successful in all attempts. There were no procedural deaths or emergency renal surgical procedures. Postprocedure azotemia was seen in 45 of 363 (12%) procedures but persisted in only 6 patients (2%), all of whom had baseline renal insufficiency. Systolic and diastolic blood pressures were significantly reduced (systolic blood pressure from 164.0 ± 28.7 to 142.4 ± 19.1 mm Hg, P < .001). At follow-up, 70% of patients had improved blood pressure control regardless of renal function. In patients with baseline renal insufficiency, 19% had improvement in serum creatinine levels at follow-up, 54% had stabilization, and 27% had deterioration. Follow-up mortality was 10% and was predicted by baseline creatinine levels (odds ratio 1.72 for each 1 mg/dL creatinine increment, 95% confidence interval 1.13-2.49) and extent of coronary artery disease (odds ratio 1.66 for each diseased coronary artery, 95% confidence interval 1.03-2.67). Angiographic restenosis was found in 21% of 102 patients overall and was less common (12%) in arteries with a reference caliber >4.5 mm (P < .01 vs caliber <4.5 mm). Neither poststenotic dilation nor severity of angiographic stenosis predicted clinical outcome. Conclusions Primary renal artery stenting can be performed safely with nearly uniform technical success. The majority of patients with hypertension or renal insufficiency derive benefit. Follow-up mortality is 5-fold higher in patients with baseline renal insufficiency. Clinical and angiographic features did not predict blood pressure or renal functional outcome. Restenosis is more common in renal arteries with a reference caliber less than 4.5 mm. (Am Heart J 2001;142:314-23.)
Atherosclerotic renal artery stenosis (RAS) is associated with hypertension and progressive renal dysfunction.1 Untreated, RAS severity tends to progress2-6 and may be associated with loss of functioning renal mass. Renal revascularization is an accepted treatment for From the aDivision of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC, and the bDivision of Cardiology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Mich. Presented in part at the 48th Annual Scientific Sessions of the American College of Cardiology, New Orleans, La, March 1999. Guest Editor for this manuscript was Peter B. Berger, MD, Mayo Clinic, Rochester, Minn. Submitted July 7, 2000; accepted May 1, 2001. Reprint requests: Robert J. Lederman, MD, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Dr, Room B1 D219, Bethesda, MD 20892. E-mail: [email protected] Copyright © 2001 by Mosby, Inc. 0002-8703/2001/$35.00 + 0 4/1/116958 doi:10.1067/mhj.2001.116958
patients with advanced renovascular disease associated with drug-refractory hypertension or recurrent pulmonary edema.7,8 Surgical reconstruction or bypass is effective but limited by procedural morbidity and mortality.9,10 Catheter-based treatment is an attractive alternative that may be tolerated by a greater proportion of affected patients. However, balloon angioplasty has a high incidence of technical failure because aorto-ostial plaques tend to recoil or leave bulky dissections.11,12 Endoluminal stents provide better angiographic and hemodynamic results than does angioplasty alone.13-16 We report a series of patients with uncontrolled hypertension or chronic renal failure along with renal artery stenosis detected for the most part during angiography for coronary artery disease. We hypothesize that renal artery stenting is safe and associated with improved blood pressure control and stabilization of renal function. In a subset of patients we also tested the
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Figure 1
Quantitative renal angiography definitions. MLD, Minimum lumen diameter.
hypothesis that angiographic restenosis is more likely in smaller-caliber renal arteries.
Transstenotic pressure gradients were not routinely measured in our laboratory to avoid catheter-induced atheroembolism.
Methods
Technique of renal artery stenting
Between June 1993 and February 1998, 361 patients underwent 436 percutaneous renal artery interventions at our institution. Sixty-one underwent balloon angioplasty alone for fibromuscular dysplasia (12 patients), atherosclerosis (0 patients), and in-stent restenosis (9 patients). The remaining 300 are described in detail here, having undergone 363 consecutive primary renal artery stent procedures involving 357 arteries. Data were collected prospectively beginning in 1996 for two thirds of the patients and retrospectively for the others.
Renal artery interventions were performed with techniques adapted from coronary stenting, in separate sessions from coronary procedures. Renal ostia typically were engaged via a femoral artery with an 8F Renal Double Curve-1 guiding catheter (Cordis, Miami, Fla). Selective angiography was performed in 2 oblique views. Heparin was administered to achieve an activated clotting time between 250 and 300 seconds. Stenoses were crossed with 0.018-inch steerable guidewires. When the vessel reference caliber exceeded 6.0 mm (the largest 0.018-inch-compatible balloon currently available), a catheter was used to exchange for a high-support 0.035-inch Rosen guidewire. Lesions were predilated and then nonarticulated medium Palmaz stents were hand crimped on the same balloon. The guiding catheter was advanced across the lesion to protect the baremounted stent from dislodgement during delivery. We took care to deploy the stent across a full thickness of aortic wall in ostial lesions, to protrude 1 to 2 mm into the aortic lumen, and to anticipate stent shortening at higher diameters. All stents were postdilated at pressures exceeding 10 atm with noncompliant balloons sized between the reference caliber and the maximal (poststenotic) vessel caliber. Sheaths were removed as soon as the activated clotting time fell below 150 seconds. Patients were treated with aspirin 325 mg daily indefinitely and ticlopidine 250 mg twice daily for 2 to 4 weeks.
Definitions and coding Baseline blood pressures were captured from the lowest measurement before procedural sedation. Inpatient and clinic measurements were used in place of catheterization suite measurements, when available. Antihypertensive medications prescribed by the primary care physician was tabulated for each patient. Multiple concurrent diuretics were coded as a single agent. Multiple agents of a single class (eg, β-adrenergic antagonists, angiotensin-converting enzyme [ACE] inhibitors) generally were coded as one agent unless they have recognized clinical utility in combination (eg, calcium channel antagonists). Hypertension was defined as systolic blood pressure (BP) exceeding 140 mm Hg or diastolic BP exceeding 90 mm Hg in multiple measurements. Malignant hypertension (MHTN) was defined as hypertension associated with life-threatening pulmonary edema, encephalopathy, or rest angina related to hypertension. Chronic renal insufficiency (CRI) was a baseline creatinine level exceeding 1.4 mg/dL. Acute renal injury particularly after exposure to intravascular contrast or ACE inhibitors did not qualify as CRI. A renal artery lesion was considered for stenting if the visually estimated diameter stenosis exceeded 70% in a patient with renal insufficiency or uncontrolled hypertension.
Quantitative angiography Quantitative arteriographic analysis was performed off-line by experienced technicians unfamiliar with the clinical outcomes with use of digital calipers calibrated against contrastfilled catheters. Two segments were measured for reference vessel caliber, both the “most-proximal normal-appearing” segments beyond proximal stenoses and a distal reference point, at which the arterial walls become parallel before the primary bifurcation (Figure 1). Lesion length was measured
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Table I. Baseline demographic characteristics for 300 patients undergoing PTRAS Age (y) 70.0 (63.1-64.6) Female sex 48.0% Duration of coronary artery disease (y) 3.89 (0.67-8.4) Extent of coronary artery disease by angiography Insignificant 18.5% 1-vessel 23.1% 2-vessel 18.5% 3-vessel 39.9% Ejection fraction 53.0% (43.0-62.0) Congestive heart failure symptoms 30.3% Diabetes mellitus 29.1% Tobacco 31.2% Hyperlipidemia 69.6% Bilateral stenosis or stenosis of solitary 41.3% patent artery Indications for PTRAS (not mutually exclusive) Hypertension 87% MHTN 13% CRI 37% Hypertension and CRI 25.3% Data are expressed as percent of total or as median (interquartile range).
between seemingly normal artery segments or extending to the ostium. The degree of poststenotic dilation was reported as the maximum caliber of the artery in this segment, unless the poststenotic segment extended beyond a major bifurcation. Poststenotic dilation was present if the caliber ratio of the poststenotic segment to the most proximal normal reference exceeded 1.2. The aortorenal angle was defined as the entry angle of the renal artery with the infrarenal aorta. Bilateral RAS was considered present if the major contralateral renal artery had an angiographic diameter stenosis >50%. Angiographic restenosis was present if diameter stenosis exceeded 50% of the proximal reference diameter on follow-up angiography.
Follow-up data collection and categorical clinical outcomes Follow-up data were collected from hospital, clinic, and primary physician records and from direct telephone inquiries with patients. Follow-up BP used both oscillometric and manual measurements. Follow-up BP is reported as the average of the 3 most recent BP recordings available after the procedure. Blood pressure improvement was defined as reduction of systolic blood pressure by at least 20 mm Hg. Late renal deterioration was defined as a rise in the serum creatinine level by at least 0.4 mg/dL to more than 1.4 mg/dL at follow-up. Late renal improvement was defined as a fall in serum creatinine by at least 0.4 mg/dL at follow-up. Transient postprocedural azotemia was defined as an acute creatinine increment exceeding 0.4 mg/dL to above 1.4 mg/dL and resolving within 30 days; otherwise it was considered sustained. Restenosis data were gathered from clinically driven angiography performed as part of peripheral and cardiac catheterization procedures.
Table II. Lesion characteristics No. of procedures Lesion type De novo stenosis Restenosis after previous angioplasty Restenosis after previous stent Aortorenal graft anastomosis Lesion location Ostial Nonostial Lesion appearance Atherosclerotic Fibromuscular dysplasia
363 94.5% 3.6% 1.4% 0.5% 95.3% 4.7% 97.8% 2.2%
Statistical analysis Clinical outcomes were analyzed on a per-patient basis. Procedural and angiographic outcomes, however, were analyzed on a per-procedure basis. Statistical analyses were performed with SPSS for Windows version 8.0 (SPSS, Chicago, Ill) by one author (R. J. L.). All tests were 2 tailed. Paired-sample t tests describe the influence of the percutaneous renal artery stent procedure (PTRAS) on clinical parameters. The influence of baseline variables on categorical outcomes was tested by independentsample t test or Mann-Whitney U test as appropriate. Independent predictors of mortality were identified by a Cox proportional hazards model, after adjustment for follow-up interval. Creatinine was logarithm-transformed for multivariate modeling, although for the sake of clinical utility odds ratios are reported only for creatinine itself.
Results Patient and vessel characteristics Baseline clinical characteristics are described in Table I. Patients were generally referred for renovascular intervention for poorly controlled hypertension requiring 2 or more medications (87%) or for renal dysfunction (37%). Only 13% had MHTN. Data regarding duration of hypertension were not captured. Lesion characteristics are described in Table II. Table III shows quantitative angiographic analysis performed on 334 (92%) available films. Poststenotic dilation was present in 45% of treated vessels. In spite of a wide variation of aortorenal angle, all lesions were treated through a transfemoral approach. Vital status was obtained for all 300 patients. Detailed clinical follow-up information was available for 267 patients (89%) after a median of 16.0 months (interquartile range 6.4-23.5) after PTRAS.
Acute outcomes and complications The PTRAS procedure was successful in all 363 lesions attempted in all patients. Palmaz medium stents (Cordis) were used in all but 2 procedures. A single 15mm P154 stent was deployed in 68.3% of patients. Two stents were deployed in 7.4% of procedures, typically
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Figure 2
Clinical outcome in subsets of patients with hypertension (HTN), CRI, or both.
to cover a distal stent-margin dissection. The largest postdilatation balloon had a mean nominal size of 6.1 ± 0.9 mm and a mean maximum inflation pressure of 12.0 ± 3.0 mm Hg. Procedural complications occurred in 6 patients. One patient died of myocardial infarction not attributable to the PTRAS procedure. He had inoperable multivessel coronary artery disease (CAD), recurrent myocardial infarction, severe hypertension, and bilateral RAS complicated by pulmonary edema requiring mechanical ventilation. Despite a technically successful PTRAS procedure, he had recurrent myocardial infarction and additional support was withdrawn after 3 days. One patient had intraprocedural thrombosis of the target renal artery. She had multiple medical problems including a baseline creatinine level of 3.7 mg/dL and a history of heparininduced thrombocytopenia with thrombosis. Anticoagulation was performed with a heparinoid but nevertheless a nonocclusive arteriographic filling defect developed after balloon predilatation, which persisted after stent placement. Intra-arterial tissue plasminogen activator infusion resolved the thrombus but renal function continued to deteriorate and the patient required hemodialysis 6 months afterward. In another patient, a partially expanded stent migrated into the aorta during deployment. It was retrieved with a balloon and deployed uneventfully in the right common iliac artery. Adjunctive abciximab was used in 3 patients. One had a nonocclusive guidewire-induced dissection of a first-order renal artery branch, which was normal on follow-up angiography 4 weeks later. Another had a hazy-appearing vessel despite stenting. Another had hypersensitivity to aspirin and received abciximab
Table III. Quantitative vessel characteristics Preprocedure Preprocedure Minimum lumen diameter (mm) Proximal reference (mm) Stenosis severity by proximal reference (%) Distal reference (mm) Stenosis severity by distal reference (%) Poststenotic dilation ratio Poststenotic dilation >20% (%) Lesion length (mm) Aortorenal angle (degrees)
Postprocedure
Mean
SD
Mean
SD
2.06
0.86
6.11
1.12
5.45 62.2
1.38 15.6
5.58 –9.7
5.08 59.3
1.31 5.18 15.1 –18.0
1.23 44.8
0.23
6.71 77
3.68 21
1.3 34.7 1.31 23.8
Quantitative off-line angiographic analysis was performed on 334 available films of 363 procedures. Definitions are listed in the Methods section. Measurement points are depicted in Figure 1.
and ticlopidine during an otherwise uneventful procedure.
BP response Systolic and diastolic BPs were significantly reduced (systolic BP from 164.0 ± 28.7 to 142.4 ± 19.1 mm Hg, P < .001) , regardless of whether PTRAS was indicated for hypertension or CRI (Table IV). Blood pressure control improved in 70% of patients. At follow-up 72 patients (34%) with hypertension used
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Figure 3
Table IV. BP and creatinine before PTRAS and after late follow-up Baseline
Serum creatinine (Cr) changes in all patients and overlapping clinical subsets with hypertension, baseline renal insufficiency, and normal renal function.
fewer antihypertensives, 83 (39%) used the same number, and 57 (27%) used more. All 3 groups of patients had equivalent frequency of blood pressure improvement. Only 2 patients with atherosclerotic RAS had normal blood pressure after withdrawal of all antihypertensive medications at follow-up. Neither clinical, procedural, nor anatomic features (recorded in the tables) at baseline predicted a favorable BP response to PTRAS. In particular, patients with poststenotic renal artery dilation were no more likely to have improved blood pressure after PTRAS than those without. Clinical response was not related to minimum lumen diameter or to percent stenosis severity. Moreover, patients with “global” RAS (involving all patent renal vessels) were no more likely in our series to derive BP benefit than those with unilateral disease.
Renal function Renal parenchymal disease was common in our patient population. CRI was present in 101 (37%) at baseline and in 142 (47%) at follow-up at a “liberal” threshold of 1.4 mg/dL. Late renal deterioration was predicted by baseline renal insufficiency (56.7% vs 23.8%, P < .01), previous MHTN (33.3% vs 11.9%, P = .05), and history of congestive heart failure (CHF) (43.3% vs 25.3%, P = .03). The long-term renal outcome of patients undergoing PTRAS is schematized in Figure 2. From the whole group serum creatinine fell significantly (>0.4 mg/dL) in 7.5%, showed no change in 78.1%, and rose in 14.4% of patients at follow-up. Among patients with renal insufficiency at baseline, 19.1% had a significant drop in creatinine at follow-up, although another 26.6% had a late creatinine rise. Pa-
All patients (n = 265) Systolic BP Diastolic BP Creatinine Antihypertensives PTRAS for hypertension (n = 227) Systolic BP Diastolic BP Creatinine Antihypertensives PTRAS for CRI (n = 94) Systolic BP Diastolic BP Creatinine Antihypertensives
Follow-up
P value
164.0 ± 28.7 142.4 ± 19.1 83.9 ± 13.7 75.7 ± 10.8 1.49 ± 0.79 1.60 ± 0.97 2.5 2.5
<.001 <.001 .052
164.7 ± 27.4 142.8 ± 18.6 84.3 ± 13.7 76.1 ± 10.9 1.37 ± 0.66 1.50 ± 0.94 2.5 2.5
<.001 .079 <.001
163.0 ± 29.1 142.6 ± 19.5 83.0 ± 12.9 74.1 ± 11.2 2.22 ± 0.90 2.34 ± 1.21 2.9 2.8
<.001 .445 <.001
Data sets are not mutually exclusive.
tients having baseline renal insufficiency constituted two thirds of patients who had a late renal deterioration. Only 7.7% of patients with normal baseline renal function had a late creatinine rise. Findings were similar when different categorization criteria were applied (20% creatinine change when serum creatinine exceeded 1.4 mg/dL). Neither clinical, procedural, nor anatomic features otherwise predict renal functional outcome. Transient postprocedural azotemia was found in 39 patients during 45 procedures. Transient azotemia was more common in patients with (22.5%) than without (4.2%) baseline CRI. Azotemia persisted (more than 1 month) in 6 patients, all of whom had baseline renal insufficiency (5.4% of patients with CRI, 2% of all patients). Overall, the majority of patients undergoing PTRAS had either a significant BP improvement or long-term stabilization of renal function (Figure 3). This was true whether they had baseline hypertension, renal insufficiency, or both. Only 3 patients had a late deterioration of renal function without significant BP improvement after PTRAS.
Malignant hypertension MHTN was the primary indication for PTRAS in 39 patients. Presenting symptoms included pulmonary edema in 25 (64%), encephalopathy in 7 (18%), and severe angina resulting from uncontrolled hypertension in 7 (18%). Compared with patients treated for benign hypertension, patients with MHTN had higher initial systolic BP (175 ± 26 vs 161 ± 27 mm Hg, P < .01), used more antihypertensive medications (3.2 ± 1.2 vs 2.3 ± 1.2, P < .01), had more frequent CRI (56% vs 24%, P < .001), and diabetes mellitus (44% vs 27%, P =
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Table V. Univariate predictors of angiographic restenosis Characteristic
No restenosis
Figure 4
P Restenosis value
No. 79 23 Procedural Balloon diameter (mm) 6.14 ± 0.73 5.38 ± 0.94 <.01 Balloon maximum 11.53 ± 3.34 11.72 ± 2.76 .82 pressure (atm) No. of stents placed 1.00 ± 0.31 1.00 ± 0.32 1.00 Total length of stents 17.24 ± 4.41 16.58 ± 4.10 .55 placed Lesion MLD preprocedure (mm) 2.04 ± 0.87 1.89 ± 0.66 .51 Lesion length (mm) 6.75 ± 3.35 7.39 ± 3.18 .47 Proximal reference 5.59 ± 1.22 4.73 ± 1.11 .01 vessel segment (mm) Minimum lumen diameter 6.06 ± 0.95 5.27 ± 0.90 <.01 poststent (mm) Poststenosis dilation 6.79 ± 1.31 5.54 ± 1.27 <.01 caliber (mm) Bilateral or solitary 58 (69.9%) 12 (60.0%) .4 RAS Follow-up angiography information was available for 102 patients.
.03), higher baseline creatinine (2.0 ± 1.1 vs 1.3 ± 0.5 mg/dL, P < .01), more extensive coronary artery disease (2.3 ± 1.1 vs 1.7 ± 1.2 vessels, P = .01), more frequent left ventricular systolic dysfunction (36.1% vs 18.4%, P = .021), and more frequent (71.1% vs 21.3%, P < .01) and severe (New York Heart Association class 3.5 ± 1.3 vs 2.8 ± 1.0, P = .03) CHF symptoms. At follow-up BP control improved to a similar extent in patients with MHTN as in those with benign hypertension, although the magnitude of BP lowering was greater. Although most patients showed long-term stabilization of renal function, there was a trend toward a worse outcome in the MHTN group (20.0% deterioration of creatinine vs 6.3%, P = .06). Mortality after 16 months was higher in patients with MHTN (23% vs 6.3%, P < .01).
Restenosis Follow-up angiography was available in 102 patients (34%) after an average of 303 days. Angiographic restenosis was found in 23 patients (21.3%). When restenosis was clinically suspected (in 26 patients), it was detected in 11 (42%) an average of 343 days after intervention. Incidental angiography detected restenosis less frequently (9 patients, 12%). No baseline clinical markers predicted restenosis. Restenosis tended to be more common among patients who had late renal functional deterioration or lack of BP improvement (61.1% vs 39.2%, P = .09). In contrast, markers of large arteries (reference vessel size, caliber of poststenotic segment, and minimum lumen diameter after stenting) were associated with a
Restenosis incidence after PTRAS according to reference vessel diameter.
significantly lower incidence of angiographic restenosis (Table V). The restenosis rate was 36.0% for vessels with a reference diameter <4.5 mm compared with 15.8% in vessels with reference diameter 4.5 to 6.0 mm (P = .068 compared with smallest vessels) and 6.5% in vessels with reference diameter exceeding 6.0 mm (P < .01 compared with smallest vessels) (Figure 4).
Mortality Vital status was determined for all 300 patients. Thirty (10%) died during the 16-month follow-up period. Mortality was higher in patients with baseline CRI (19.1% vs 4.3%, P < .001); these patients constituted 70% of all deaths. Other univariate predictors of death (Table VI) included serum creatinine, MHTN, CHF, left ventricular dysfunction, number of diseased coronary arteries, and significant stenosis of all remaining renal arteries (“global” RAS). Multivariate regression identified baseline creatinine (odds ratio 1.72 for each 1-mg/dL creatinine increment, 95% confidence interval 1.13-2.49) and extent of coronary artery disease (odds ratio 1.66 for each diseased epicardial coronary artery, 95% confidence interval 1.03-2.67) as independent predictors of mortality.
Discussion This is the largest published single-center series of PTRAS. PTRAS was safe and was performed with high technical success. The majority of patients with RAS and hypertension or renal insufficiency seemed to derive clinical benefit.
Limitations This study is limited by the absence of a control group of patients treated pharmacologically, by concur-
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Table VI. Predictors of death during follow-up
Characteristic Age (y)* Female sex CRI Creatinine† MHTN Systolic BP Diastolic BP Ejection fraction <0.45 No. of CAD vessels CHF Diabetes mellitus Tobacco history Hyperlipidemia “Global” RAS
Alive at follow-up (n = 270)
Dead at follow-up (n = 30)
67.9 ± 9.4 132 (48.9%) 90 (33.3%) 1.4 ± 0.7 30 (11.1%) 162.8 ± 28.8 83.5 ± 13.8 43 (22.9%) 1.7 ± 1.2 69 (26.8%) 75 (27.8%) 185 (68.8%) 181 (67.3%) 106 (39.3%)
70.2 ± 7.2 12 (40.0%) 21 (70.0%) 2.0 ± 1.0 9 (30.0%) 167.5 ± 25.9 83.8 ± 12.3 12 (44.4%) 2.4 ± 1.0 18 (60.0%) 12 (40.0%) 23 (76.7%) 15 (50.0%) 18 (60.0%)
Univariate P value .210 .360 <.001 <.001 .038 .386 .885 .043 .003 .001 .211 .351 .084 .029
Multivariate P value NS NS — .004 NS — — NS .039 NS — — NS NS
OR (95% CI)
1.72 (1.13-2.49)
1.66 (1.03-2.67)
OR, Odds ratio; CI, confidence interval; NS, not significant. *Categorical age > median in Cox regression analysis. †Log-transformed for Cox regression analysis, data are reported for untransformed creatinine.
rent pharmacotherapy that has an impact on both BP and glomerular filtration rate, by retrospective data collection, by heterogeneous follow-up of BP and creatinine data at variable time points and at multiple sites, and by nonsystematic follow-up angiography. In particular, BP recordings were extracted from charts. Manual sphygmomanometry has been shown to exaggerate the blood pressure–lowering effect of renal artery angioplasty compared with automated oscillometric and ambulatory BP measurements.17
Efficacy PTRAS lowered systolic and diastolic BPs in >70% of our patients after a 16-month mean follow-up, to a range shown desirable in large contemporary clinical trials.18-20 BP lowering was equivalent in patients with normal and abnormal renal function. In contrast to other published series of PTRAS for atherosclerotic RAS,14,21-23 only 2 patients in our mostly elderly population were “cured” of hypertension. Undoubtedly the majority of our patients had concurrent essential hypertension or parenchymal renal disease.24 Overall, patients used the same mean number of antihypertensive medications at follow-up, although 27% used more antihypertensive medications than they had previously. This probably reflects the intensified medical therapy and risk factor reduction patients often undertake after identification of significant coronary and peripheral artery disease. In our patients the average serum creatinine level, an estimate of glomerular filtration rate,25 tended to increase during follow-up (1.49 ± 0.79 vs 1.60 ± 0.97 mg/dL, P = .05). This may reflect either the natural history of renal insufficiency or procedural renal injury. A
transient creatinine increase, presumably related to contrast nephrotoxicity or renal atheroembolism, was seen in 13% of our patients and was more common in those with pre-existing renal failure (22.5%) than without (4.2%). Creatinine returned to normal in almost all patients within 30 days. Sustained azotemia was detected in only 2% of patients after the first month. Even after relief of renal artery obstruction, many of our patients had additional renal comorbidity, including irreversible parenchymal injury, diabetic glomerulopathy, subclinical atheroembolism, and essential hypertension. In some patients correction of RAS by stenting might be expected to delay or halt the decline in renal function by improving renal blood flow and blood pressure control. Indeed, there is evidence that percutaneous26,27 and surgical renal revascularization28,29 reduce the rate of renal functional deterioration despite a continued rise in serum creatinine. We do not know the magnitude or tempo of renal functional deterioration had our patients not undergone PTRAS. Ultimately this question can be answered only in a randomized comparison of invasive and medical therapy. Nineteen percent of patients in this series with baseline CRI had significant improvement in glomerular filtration. We were careful not to misclassify patients recovering from acute renal (ie, contrast) injury as having baseline CRI. Finally, we found no clinical, angiographic, or procedural markers that helped predict clinical improvement in BP or renal insufficiency after the procedure. Patients treated for bilateral or global RAS were not more likely to derive improved BP control than patients treated for unilateral RAS, in contrast to other reports.30 This finding is tempered, however, by the high inci-
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dence of “incompletely revascularized” bilateral RAS. Angiographically more severe stenoses were not associated with better clinical outcome than less severe stenoses among patients selected for intervention. Finally, poststenotic dilation, considered a marker of chronic hemodynamically significant flow perturbation, did not predict improved BP response, in contrast to other reports.31
Quantitative renal angiography and the results of stenting There are no uniform standards for quantitative interpretation of renal angiograms. Normal main renal arteries have a fusiform proximal segment and taper distally before the primary branch (Figure 1). Choosing a “normal” renal artery reference segment poses a challenge analogous to that in carotid atherosclerosis, in which plaque involves a bifurcation and a dilated carotid bulb. In the North American Symptomatic Carotid Endarterectomy Trial (NASCET),32 the reference caliber was chosen as the first downstream internal carotid segment to have parallel arterial walls, analogous to our “most distal normal” reference. In renal arteries the distal reference may be more physiologically significant because it represents the narrowest segment of “normal” artery before it bifurcates. In this study quantitative mean stenosis severity was 61.4% with use of a distal reference site compared with 70% when the widest portion of the artery was used. Most studies, however, use the latter strategy. Both measurements suggest a qualitative exaggeration of stenosis severity by the angiographer, a well-recognized phenomenon in coronary angiography.33 The presence of post-stenotic dilation (44% in this study) further complicates quantitative analysis and also may present a technical challenge to optimizing the size of the endoluminal stent. In our laboratory proximal and ostial stenosis are treated with the proximal stent extending 1 to 2 mm into the aortic lumen and the distal stent ending within the “shoulder” segment of the poststenotic or fusiform segment of the main renal artery.
Restenosis Follow-up angiography was performed nonsystematically in 102 (34%) patients, generally as part of coronary or other peripheral artery angiographic procedures. Binary angiographic restenosis was found in 21.3%. In only half of these patients, restenosis had been suspected clinically. These restenosis rates are comparable to those of other reported series.14-16 This is the first report associating renal artery restenosis with progressively smaller reference vessel caliber. We found a high incidence of in-stent renal artery restenosis (36%) in the tercile of patients having small vessels <4.5 mm in diameter compared with larger vessels (12%). Aortorenal atherosclerotic plaques, which are sub-
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stantially bulkier than coronary artery plaques, apparently respond differently to stenting. Angiographic coronary restenosis is only 16% after stenting arteries having a mean 3.0-mm reference caliber.34 However, balloon angioplasty without stenting has an even higher incidence of technical failure and restenosis (50%-80%) in these aorto-ostial lesions.11,12 On the basis of our observation, renal arteries having a reference caliber ≤4.5 mm are less attractive targets for percutaneous therapy and consideration should be given to medical or surgical management. Conversely, renal arteries larger than 4.5 mm have an acceptably low incidence of angiographic restenosis.
Mortality There was a relatively high mortality of 10% after 16 months of follow-up. Baseline creatinine and extent of CAD were independent predictors of mortality reflecting the severity of diffuse atherosclerosis in this population. Previous studies have demonstrated that the presence of significant RAS is an independent predictor of CAD and mortality.35,36
Complications Early experiences with PTRAS reported a worrisome incidence of major complications including renal artery rupture, perforation, thrombosis, renal and systemic atheroembolism, infection, procedural technical failure, major hemorrhage, and death.21,23,26,37-42 A noteworthy feature of our experience is the uniform technical success rate and high procedural safety. In our series there were no renal artery perforations or ruptures requiring emergency surgical renal salvage. The only periprocedural arterial thrombosis occurred in a woman with known heparin-associated thrombocytopenia-thrombosis despite heparinoid anticoagulation. Transient azotemia was common in patients with baseline renal insufficiency, but sustained renal injury was infrequent (2.0% of patients overall). The appreciably lower incidence of complications in recent reports14-16,22 may reflect the translation of meticulous coronary stenting technique to noncoronary territories. This includes scrupulous anticoagulation, use of soft steerable guidewires, careful device sizing using quantitative angiography, low-pressure predilatation before stent deployment, stent deployment with the guiding catheter as delivery sheath, and high-pressure stent postdilatation taking care not to traumatize the distal vessel with the balloon. By comparison, surgical revascularization, although effective, confers a comparatively higher risk of procedural morbidity and mortality.9,10,43-46
Conclusions In experienced hands PTRAS can be performed with a high degree of technical success at low risk to the
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patient. In arteries having a reference caliber greater than 4.5 mm, angiographic restenosis is unusual. PTRAS may therefore be the treatment of choice for selected patients with significant atherosclerotic RAS. Although the majority of patients derived clinical benefit, a randomized comparison is warranted between aggressive pharmacologic and interventional therapy. We thank Mark Urtz and Thomas Hoffman for quantitative arteriographic measurements; Laura Gaulden, Patty Hoffman, and Sara and Jan Wellendorff for telephone follow-up; David Bruckman for review of statistical procedures; Hugh Wells and Laura Waugh for data entry; and Joseph Greenfield and Eric Bates for their invaluable critical review.
References 1. Novick A, Scoble J, Hamilton G. Renal vascular disease. London: WB Saunders; 1996. 2. Wollenweber J, Sheps SG, Davis GD. Clinical course of atherosclerotic renovascular disease. Am J Cardiol 1968;21:60-71. 3. Dean RH, Kieffer RW, Smith BM, et al. Renovascular hypertension: anatomic and renal function changes during drug therapy. Arch Surg 1981;116:1408-15. 4. Crowley J, Santos R, Peter R, et al. Progression of renal artery stenosis in patients undergoing cardiac catheterization. Am Heart J 1998;136:918-8. 5. Caps MT, Perissinotto C, Zierler RE, et al. Prospective study of atherosclerotic disease progression in the renal artery. Circulation 1998;98:2866-72. 6. Caps MT, Zierler RE, Polissar NL, et al. Risk of atrophy in kidneys with atherosclerotic renal artery stenosis. Kidney Int 1998;53:73542. 7. Messina LM, Zelenock GB, Yao KA, et al. Renal revascularization for recurrent pulmonary edema in patients with poorly controlled hypertension and renal insufficiency: a distinct subgroup of patients with arteriosclerotic renal artery occlusive disease. J Vasc Surg 1992;15:73-82. 8. Pickering TG, Herman L, Devereux RB, et al. Recurrent pulmonary oedema in hypertension due to bilateral renal artery stenosis: treatment by angioplasty or surgical revascularisation. Lancet 1988;2:551-2. 9. Stanley JC. The evolution of surgery for renovascular occlusive disease. Cardiovasc Surg 1994;2:195-202. 10. Cambria RP, Brewster DC, L’Italien GJ, et al. The durability of different reconstructive techniques for atherosclerotic renal artery disease. J Vasc Surg 1994;20:76-87. 11. Bonelli FS, McKusick MA, Textor SC, et al. Renal artery angioplasty: technical results and clinical outcome in 320 patients Mayo. Clin Proc 1995;70:1041-52. 12. Sos TA, Pickering TG, Sniderman K, et al. Percutaneous transluminal renal angioplasty in renovascular hypertension due to atheroma or fibromuscular dysplasia. N Engl J Med 1983;309:274-9. 13. Dorros G, Prince C, Mathiak L. Stenting of a renal artery stenosis achieves better relief of the obstructive lesion than balloon angioplasty. Cathet Cardiovasc Diagn 1993;29:191-8. 14. Blum U, Krumme B, Flugel P, et al. Treatment of ostial renal-artery stenoses with vascular endoprostheses after unsuccessful balloon angioplasty. N Engl J Med 1997;336:459-65.
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15. Dorros G, Jaff M, Mathiak L, et al. Four-year follow-up of PalmazSchatz stent revascularization for atherosclerotic renal artery stenosis. Circulation 1998;98:642-7. 16. White CJ, Ramee SR, Collins TJ, et al. Renal artery stent placement: utility in lesions difficult to treat with balloon angioplasty. J Am Coll Cardiol 1997;30:1445-50. 17. Plouin PF, Chatellier G, Darne B, et al. Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis: a randomized trial. Essai Multicentrique Medicaments vs Angioplastie (EMMA) Study Group. Hypertension 1998;31:823-9. 18. Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998; 351:1755-62. 19. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991;265:3255-64. 20. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997;157:2413-46. 21. Boisclair C, Therasse E, Oliva VL, et al. Treatment of renal angioplasty failure by percutaneous renal artery stenting with Palmaz stents: midterm technical and clinical results. AJR Am J Roentgenol 1997;168:245-51. 22. Henry M, Amor M, Henry I, et al. Renal arterial stenting: a 7 year single center experience with a series of 206 stented arteries [abstract]. J Am Coll Cardiol 1998;31(2 Suppl A):453A. 23. Thorpe A, Moss J, Harden P, et al. Renal artery stenting: a 6-year single-center experience with a series of 151 arteries with stents. J Vasc Intervent Radiol 1997;8(2 Suppl):246. 24. Streeten DH, Anderson GH Jr, Wagner S. Effect of age on response of secondary hypertension to specific treatment. Am J Hypertens 1990;3:360-5. 25. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461-70. 26. Harden PN, MacLeod MJ, Rodger RS, et al. Effect of renal-artery stenting on progression of renovascular renal failure Lancet 1997; 349:1133-6. 27. Ahuja R, Poler S, Rocha-Singh K. Palmaz stenting reverses progressive renal dysfunction in patients with global renal ischemia due to atherosclerotic renal artery stenosis [abstract]. J Am Coll Cardiol 1999;33(A Suppl):42A. 28. Dean RH, Tribble RW, Hansen KJ, et al. Evolution of renal insufficiency in ischemic nephropathy. Ann Surg 1991;213:446-56. 29. van Rooden CJ, van Bockel JH, De Backer GG, et al. Long-term outcome of surgical revascularization in ischemic nephropathy: normalization of average decline in renal function. J Vasc Surg 1999;29: 1037-49. 30. Rocha-Singh KJ, Mishkel GJ, Katholi RE, et al. Clinical predictors of improved long-term blood pressure control after successful stenting of hypertensive patients with obstructive renal artery atherosclerosis. Catheter Cardiovasc Interv 1999;47:167-72. 31. Prince MR, Schoenberg SO, Ward JS, et al. Hemodynamically significant atherosclerotic renal artery stenosis: MR angiographic features. Radiology 1997;205:128-36. 32. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis: North American Symptomatic
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33.
34.
35. 36. 37.
38.
39.
Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991; 325:445-53. Beauman GJ, Vogel RA. Accuracy of individual and panel visual interpretations of coronary arteriograms: implications for clinical decisions. J Am Coll Cardiol 1990;16:108-13. Serruys PW, van Hout B, Bonnier H, et al. Randomised comparison of implantation of heparin-coated stents with balloon angioplasty in selected patients with coronary artery disease (Benestent II). Lancet 1998;352:673-81. Valentine RJ, Clagett GP, Miller GL, et al. The coronary risk of unsuspected renal artery stenosis. J Vasc Surg 1993;18:433-40. Conlon PJ, Athirakul K, Kovalik E, et al. Survival in renal vascular disease. J Am Soc Nephrol 1998;9:252-6. Iannone LA, Underwood PL, Nath A, et al. Effect of primary balloon expandable renal artery stents on long-term patency, renal function, and blood pressure in hypertensive and renal insufficient patients with renal artery stenosis. Cathet Cardiovasc Diagn 1996;37:243-50. van de Ven PJ, Beutler JJ, Kaatee R, et al. Transluminal vascular stent for ostial atherosclerotic renal artery stenosis. Lancet 1995; 346:672-4. MacLeod MJ, Connell JM, Harden PN, et al. Transluminal vascular stents for ostial atherosclerotic renal artery stenosis. Lancet 1995; 346:1109-10.
Lederman et al 323
40. Trost D, Sos T, Jagust M, et al. Palmaz stents to treat ostial renal artery stenoses in persons with hypertension and azotemia: immediate and intermediate results. J Vasc Intervent Radiol 1997;8(2 Suppl):245. 41. Rundback JH, Gray RJ, Rozenblit G, et al. Renal artery stent placement for the management of ischemic nephropathy. J Vasc Interv Radiol 1998;9:413-20. 42. Deitch J, Hansen K, Regan J, et al. Infected renal artery pseudoaneurysm and mycotic aortic aneurysm after percutaneous transluminal renal artery angioplasty and stent placement in a patient with a solitary kidney. J Vasc Surg 1998;28:340-4. 43. Novick AC, Ziegelbaum M, Vidt DG, et al. Trends in surgical revascularization for renal artery disease: ten years’ experience. JAMA 1987;257:498-501. 44. Bergan JJ, Wilson SE, Wolf G, et al. Unexpected, late cardiovascular effects of surgery for peripheral artery disease: Veterans Affairs Cooperative Study 199. Arch Surg 1992;127:1119-23. 45. Hansen KJ, Starr SM, Sands RE, et al. Contemporary surgical management of renovascular disease. J Vasc Surg 1992;16:319-30. 46. Weibull H, Bergqvist D, Bergentz SE, et al. Percutaneous transluminal renal angioplasty versus surgical reconstruction of atherosclerotic renal artery stenosis: a prospective randomized study. J Vasc Surg 1993;18:841-50.