The Dutch Renal Artery Stenosis Intervention Cooperative (DRASTIC) Study: rationale, design and inclusion data

RATIONALE: Renal artery stenosis may lead to renovascular hypertension, risking multiple organ damage including damage to the contralateral kidney. Progression of stenosis may impair the function of the affected kidney. It is important to identify individuals with this disease among hypertensive patients. The first aim of the Dutch Renal Artery Stenosis Intervention Cooperative (DRASTIC) study is to assess the prevalence of renal artery stenosis in patients with well-defined forms of drug-resistant hypertension, and to determine the predictive value of clinical characteristics and diagnostic tests in these pre-selected patients. With regard to treatment, the effect of renal angioplasty on hypertension is disappointing in atherosclerotic stenosis and technical failure frequently occurs. Therefore, the second aim is to compare the effects of balloon angioplasty and antihypertensive medication on blood pressure in patients with atherosclerotic renal artery stenosis. DESIGN HYPERTENSIVE: patients receiving standard antihypertensive medication in whom diastolic blood pressure remained > or =95 mmHg during three consecutive visits to the outpatient clinic underwent full diagnostic work-up, including renal arteriography. The prevalence of renal artery stenosis in this well-defined patient group was then established, and the predictive value of the various diagnostic tests was assessed. Patients with an atherosclerotic renal artery stenosis of > or =50% were then randomly assigned to balloon angioplasty or to treatment with antihypertensive drugs. After 1 year of intensive follow-up of blood pressure and renal function, re-arteriography was performed. CONCLUSION: In total, 1205 patients have been included in the study, about 500 have received diagnostic work-up, and it is expected that 100 patients will be randomly assigned for renal angioplasty or medical treatment.     

Bovine endometrial retinol-binding protein secretion, messenger ribonucleic acid expression, and cellular localization during the estrous cycle and early pregnancy

OBJECTIVES: We assessed the safety and efficacy of stent placement in patients with poorly controlled hypertension and renal artery stenoses, which are difficult to treat with balloon angioplasty alone. BACKGROUND: Preliminary experience with stent placement suggests improved results over balloon angioplasty alone in patients with atherosclerotic renal artery stenosis. METHODS: Balloon-expandable stents were placed in 100 consecutive patients (133 renal arteries) with hypertension and renal artery stenosis. Sixty-seven of the patients had unilateral renal artery stenosis treated and 33 had bilateral renal artery stenoses treated with stents placed in both renal arteries. RESULTS: Angiographic success, as determined by quantitative angiography, was obtained in 132 (99%) of 133 lesions. Early clinical success was achieved in 76% of the patients. Six months after stent placement, the systolic blood pressure was reduced from 173 +/- 25 to 147 +/- 23 mm Hg (p < 0.001); the diastolic pressure from 88 +/- 17 to 76 +/- 12 mm Hg (p < 0.001); and the mean number of antihypertensive medications per patient from 2.6 +/- 1 to 2.0 +/- 0.9 (p < 0.001). Angiographic follow-up at a mean of 8.7 +/- 5.0 months in 67 patients revealed restenosis (>50% diameter narrowing) in 15 (19%) of 80 stented vessels. CONCLUSIONS: Renal artery stenting is an effective treatment for renovascular hypertension, with a low angiographic restenosis rate. Stent placement appears to be a very attractive therapy in patients with lesions difficult to treat with balloon angioplasty such as renal aorto-ostial lesions and restenotic lesions, as well as after a suboptimal balloon angioplasty result.     

Treatment of renal artery stenosis with intra-arterial stents

In some patients with hypertension or renal insufficiency, renal artery stenosis can play a causative part. If fibromuscular dysplasia is the pathology of the stenosis, treatment of the stenosis by transluminal percutaneous renal angioplasty (TPRA) results in improvement of the concomitant hypertension in 80-90% of the patients. In case of atherosclerotic lesions 50% of the patients benefit by such treatment. In renal insufficiency TPRA of atherosclerotic lesions results in improvement of renal function in only one third of the patients. As restenosis and elastic recoil are seen as the prime determinants of this lack of success in atherosclerosis, intravascular stents were developed with the aim to accomplish a permanent dilation of the arterial lumen. In recent studies stent placement resulted in cure of high blood pressure in 0-16% of the patients and in improvement in 35-70%. The percentage of improvement must be viewed with caution because of the open design of these studies. Improvement of renal function was reported in 7-36% of the patients and worsening in 8-18%. Based on these outcomes stent placement in stenosed renal arteries should not be regarded as a routine clinical treatment.     

A case of renal artery stenosis after transplantation: can losartan be more accurate than captopril renography?

Hypertension is a common complication observed after renal transplantation. If the hypertension is of renovascular origin, transluminal angioplasty or surgery of the renal artery stenosis can lead help cure the hypertension. The blood pressure of a 31-year-old man who underwent renal transplantation 2 years earlier gradually increased. Arteriography showed stenosis (>80%) in the two branches of the renal artery. To help confirm the presence of renovascular hypertension, captopril renography was performed but showed no significant changes compared with baseline renography. Renography was performed again after losartan administration and showed impaired renal function. In this case, losartan renography was more useful than captopril in suggesting renovascular hypertension.     

Renal artery angioplasty for renovascular hypertension and preservation of renal function: long-term angiographic and clinical follow-up

OBJECTIVE: Percutaneous transluminal angioplasty of stenoses of the renal artery can be used to treat hypertension and renal insufficiency. Although many studies have been published on the short-term results of this procedure, few long-term studies are available. SUBJECTS AND METHODS: One hundred ninety-five patients (123 men and 72 women 19-79 years old; mean age, 56 years) with stenosis of the renal artery and hypertension underwent renal percutaneous transluminal angioplasty at our institution. The stenosis was unilateral in 66% of patients, bilateral in 26%, and in a solitary functioning kidney in 8%. Renal insufficiency was present in 31% of patients. After renal percutaneous transluminal angioplasty, long-term clinical and angiographic follow-up was evaluated by life-table analysis. RESULTS: In patients with fibromuscular disease, blood pressure returned to normal in 57%, improved in 21%, and was unchanged in 21%. In patients with atherosclerotic stenosis, blood pressure returned to normal in 12%, improved in 51%, and was unchanged in 37%. After percutaneous transluminal angioplasty, renal function improved in 48% of patients with renal insufficiency due to bilateral stenosis or stenosis in the single functioning kidney, whereas none of the patients with unilateral stenosis of renal artery and renal insufficiency had any notable improvement. Long-term follow-up showed a high rate (82%) of patency of revascularized arteries and a low rate (21%) of hypertension recurrence at 5 years. CONCLUSION: Renal percutaneous transluminal angioplasty is useful for treating hypertension and for reestablishing renal function. Its effects on blood pressure and renal function are long-lasting in the large majority of patients.     

Captopril renal scintigraphy in renovascular hypertension

Renovascular disease is a common cause of secondary hypertension. Renal artery stenosis is present in up to one third of patients with clinical markers suggestive of renovascular hypertension, such as hypertension refractory to medical management, severe hypertension in a young patient and worsening of renal function after the use of an angiotensin-converting enzyme inhibitor. Early discovery of renal artery stenosis may allow amelioration or cure of the hypertension and halt progressive loss of renal function. Although renal arteriography remains the gold-standard aid to diagnosis and to planning surgical intervention, it is an invasive procedure that may cause deterioration of renal function. In the presence of renal artery stenosis, glomerular filtration is maintained by angiotensin. Administration of captopril in renal scintigraphy removes this compensatory mechanism and causes a temporary impairment of renal function in the affected kidney. Nuclear tracers can visualize this impairment, thus allowing assessment of the physiologic significance of a renal artery stenosis. The test can be done as a outpatient procedure.     

Detection of main renal artery stenosis using phase-contrast cine MR angiography

OBJECTIVE: The purpose of our study was to assess the ability of phase-contrast cine MR angiography to detect the presence of main renal artery stenosis. SUBJECTS AND METHODS: We prospectively evaluated 75 hypertensive patients form main renal artery stenosis using phase-contrast cine MR angiography. Each main renal artery was evaluated as normal or abnormal. Thirty-seven of the 75 patients underwent conventional arteriography or intraarterial digital subtraction arteriography; these results were compared with the MR angiographic interpretations. Only those patients who had confirmatory arteriography were included in the statistical analysis. RESULTS: Thirty-six main renal arteries interpreted as normal by MR angiography were found to be without a focal stenosis on invasive arteriography. MR angiography suggested 32 main renal artery stenoses; invasive arteriography showed 29 of these as stenoses. Three main renal arteries that were interpreted as having focal stenoses by MR angiography were shown to be not stenotic by invasive arteriography. Three other patients had diffusely narrowed main renal arteries bilaterally without a focal stenosis on MR angiography; bilateral proximal renal artery stenoses were seen at arteriography in two of these patients, and diffusely narrowed main renal arteries were seen in the third patient. Thus, the sensitivity of phase-contrast cine MR angiography for detecting a focal stenosis or abnormal main renal artery was 100% (95% confidence interval, 88-100%) and the specificity was 93% (95% confidence interval, 80-99%). The kappa coefficient was 0.85 with a standard error of 0.08. CONCLUSION: Phase-contrast cine MR angiography had a high degree of accuracy and a high negative predictive value in detecting the presence of main renal artery stenoses and may be a good screening technique for renovascular hypertension.     

Detecting and treating arteriosclerotic renovascular hypertension

Renovascular hypertension is the most prevalent form of surgically remediable hypertension. With appropriate selection of operative candidates, a high rate of cure or improvement may be anticipated. Favorable results justify revascularization in hypertensive patients with focal arteriosclerotic renal artery disease. The absence of advanced arteriosclerosis provides the most valid basis for predicting long-term survival following revascularization. Patients with clinically demonstrable diffuse arteriosclerotic disease are preferably treated medically; we consider them candidates for surgery only if drug therapy cannot control blood pressure. Renal revascularization does not appear to alter the inexorable progression of concomitant generalized arteriosclerosis. Revascularization rather than nephrectomy is the primary surgical therapy for renal artery stenosis in properly selected patients.     

A clinical prediction rule for renal artery stenosis

BACKGROUND: Renal artery stenosis is a rare cause of hypertension. The gold standard for diagnosing renal artery stenosis, renal angiography, is invasive and costly. OBJECTIVE: To develop a prediction rule for renal artery stenosis from clinical characteristics that can be used to select patients for renal angiography. DESIGN: Logistic regression analysis of data from a prospective cohort of patients suspected of having renal artery stenosis. A prediction rule was derived from the regression model for use in clinical practice. SETTING: 26 hypertension clinics in The Netherlands. PATIENTS: 477 hypertensive patients who underwent renal angiography because they had drug-resistant hypertension or an increase in serum creatinine concentration during therapy with angiotensin-converting enzyme inhibitors. RESULTS: Age, sex, atherosclerotic vascular disease, recent onset of hypertension, smoking history, body mass index, presence of an abdominal bruit, serum creatinine concentration, and serum cholesterol level were selected as predictors. The regression model was reliable (goodness-of-fit test, P > 0.2) and discriminated well between patients with stenosis and those with essential hypertension (area under the receiver-operating characteristic curve, 0.84). The diagnostic accuracy of the regression model was similar to that of renal scintigraphy, which had a sensitivity of 72% and a specificity of 90%. CONCLUSIONS: In the diagnostic workup of patients suspected of having renal artery stenosis, the clinical prediction rule can be considered as an alternative to renal scintigraphy. It can help to select patients for renal angiography in an efficient manner by reducing the number of angiographic procedures without the risk for missing many renal artery stenoses.     

Effects of intraaortic balloon pumping on septal arterial blood flow velocity waveform during severe left main coronary artery stenosis

OBJECTIVES: We sought to evaluate the effect of intraaortic balloon pumping on the phasic blood velocity waveform into myocardium with severe coronary artery stenosis. BACKGROUND: In the presence of severe coronary artery stenosis, it is not clear whether intraaortic balloon pumping augments intramyocardial inflow during diastole or changes systolic retrograde blood flow from the myocardium to the extramural coronary arteries. METHODS: Using anesthetized open chest dogs (n=7), we introduced severe stenosis in the left main coronary artery to reduce the poststenotic pressure to approximately 60 mm Hg (>90% diameter stenosis). Septal arterial blood flow velocities were measured with a 20-MHz, 80-channel ultrasound pulsed Doppler velocimeter. Left anterior descending arterial flow, aortic pressure and poststenotic distal coronary pressure were measured simultaneously. The diastolic anterograde flow integral and systolic retrograde flow integral were compared in the presence and absence of intraaortic balloon pumping. RESULTS: Although intraaortic balloon pumping augmented diastolic aortic pressure, this pressure increase was not effectively transmitted through stenosis. Septal arterial diastolic flow velocity was not augmented, and left anterior descending arterial flow was unchanged during intraaortic balloon pumping. CONCLUSIONS: In the presence of severe coronary artery stenosis, intraaortic balloon pumping failed to increase diastolic inflow in the myocardium and did not enhance systolic retrograde flow from the myocardium to the extramural coronary artery. Thus, the major effect of intraaortic balloon pumping on the ischemic heart with severe coronary artery stenosis may be achieved by reducing oxygen demand by systolic unloading.     

Management of the patient with renovascular hypertension

Renal artery stenosis, either fibromuscular or atheromatous, is probably the most common cause of secondary hypertension in man. Both of these diseases are active, ongoing processes that may be ameliorated but not cured by medical or surgical treatment. The clinical history and examination of the patient with hypertension may help differentiate renovascular hypertension from essential hypertension. The presence of a systolic-diastolic or continuous bruit is often an indicator of severe renal artery stenosis. Systemic hypertension is the physiologic consequence of significant renal artery stenosis. Knowledge of the basic concepts of the renin-angiotensin-aldosterone system, as has evolved from experimental models of renovascular hypertension, forms the basis for understanding the process of evaluation and treatment of such patients. The treatment of choice for the patient with severe hypertension and a functionally significant renovascular lesion is surgical--both in terms of successful treatment of hypertension and improved long-term prognosis. Diligent periodic reevaluation of these patients as well as those with less severe hypertension who are receiving medical treatment enables the physician to select the proper management that offers optimal control of patient blood pressure and avoids target-organ damage to the kidneys, central nervous system, or cardiovascular system.     

Duplex sonography of renal arteries as a diagnostic tool in hypertensive children

Computed duplex sonography was used to examine the renal arteries in 36 hypertensive children and adolescents (ages 4-17 years) with arterial hypertension of either renal or non-renal origin. Time-averaged flow velocities, maximum blood flow velocities as well as absolute renal blood flow and renal blood flow per gram kidney weight were measured. Normal flow velocities and normal to elevated renal blood flow volume was found in patients with acute glomerulonephritis and those with signs of chronic glomerulonephritis onset. Patients having advanced stages of chronic glomerulonephritis, on the other hand, were characterized by lower levels of all parameters. Unilateral renal artery stenosis was diagnosed correctly in four patients, although one intra-renal artery stenosis escaped imaging. Scarred kidneys exhibited low-normal or reduced flow velocities and renal blood flow volumes corresponded roughly to kidney size and preservation of normal kidney structure. Hypertension in some patients with normal kidneys showed a tendency to cause higher renal blood flow without consistent acceleration of blood flow velocities. We conclude that duplex sonography is a suitable primary diagnostic tool in measuring blood flow velocities and absolute renal blood flow volume in hypertensive children, thus facilitating the choice of the next diagnostic step.     

Reconstruction of renal artery aneurysms. Vessel morphology and clinical results

OBJECTIVE: To analyse retrospectively from case notes and follow-up examinations the effectiveness of vascular surgery for renal artery aneurysm (RAA). PATIENTS AND METHODS: Operations for uni- or bilateral RAA were performed, between January 1978 and December 1996, on 61 patients (39 women, 22 men; mean age 47.4 years), 81% with arterial hypertension. Extracorporeal reconstruction with renal autotransplantation was performed in 4 of the patients. Clinical examination and duplex sonography or angiography were performed a mean of 58.4 months postoperatively. RESULTS: Postoperative morbidity rate related to the surgery was 13%; there were no early postoperative death. At the time of follow-up 80% of the reconstructed renal arteries were patent. 26% of hypertensive were cured of the hypertension, while the blood pressure was significantly reduced in 40%. CONCLUSIONS: Vascular reconstruction of RAA can be effective so that primary nephrectomy is no longer indicated. Reconstruction in situ can usually be successfully performed, reducing operative time and reducing surgical trauma. The operation is indicated in any RAA of greater than 2 cm diameter, in all patients with hypertension and renal artery stenosis, and also for smaller aneurysms in patients in good general health and in women of child-bearing age.     

Effects of leukotrienes on bronchial secretions

To evaluate the reliability of Doppler-ultrasonography in identifying children with renal artery stenosis among those with hypertension, we compared Doppler ultrasonography results in 29 hypertensive children (mean age: 8.3 +/- 4.7 years) with angiography. Doppler-ultrasonography and arteriography were performed within a period less than two months. First, we established normal values in 40 normotensive children (mean age: 8.4 +/- 4.5 years). The diagnosis of renal artery stenosis was settled when maximal systolic velocities where > or = to 1.70 m.s-1. Peak systolic velocities values of Doppler-ultrasonography were significantly higher in patients with proven angiographic renal artery stenosis (3.56 +/- 0.70 m.s-1) than in hypertensive patients with normal renal arteries at angiography (1.02 +/- 0.29 m.s-1, p < 0.0001), and than in normotensive healthy children (1.05 +/- 0.33 m.s-1, p < 0.0001). We observed 3 false negative and 2 false positive diagnoses with Doppler-ultrasonography. Of the 3 false negatives, one had a stenosis on a right and posterior segmental artery and the other had bilateral and multiply intra-renal artery stenosis with few hemodynamic significance. The 2 false positives were due to a sinuous main renal artery and to a technical mistake, respectively. In another patient, Doppler-ultrasonography revealed a tight main renal artery stenosis, not detected by arteriography. Renal artery stenosis was subsequently confirmed by a second arteriography. Our results showed a sensitivity of 88%, a specificity of 93%, a positive predictive value of 92% and a negative predictive value of 89%, demonstrating the reliability of Doppler-ultrasonography for the diagnosis of renal artery stenosis in hypertensive children. With the use of a rigorous methodology and the increasing experience of the operators, diagnostic errors of renal artery stenosis are currently avoidable. Nevertheless, it is not excluded that intra-renal artery stenosis with few hemodynamic significance might be missed by Doppler-ultrasonography.     

Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis: a randomized trial. Essai Multicentrique Medicaments vs Angioplastie (EMMA) Study Group

Data for the effects on blood pressure of renal artery balloon angioplasty are mostly from uncontrolled studies. The aim of this study was to document the efficacy and safety of angioplasty for lowering blood pressure in patients with atherosclerotic renal artery stenosis. Patients were randomly assigned antihypertensive drug treatment (control group, n = 26) or angioplasty (n = 23). Twenty-four-hour ambulatory blood pressure, the primary end point, was measured at baseline and at termination. Termination took place 6 months after randomization or earlier in patients who developed refractory hypertension. In those allocated angioplasty, antihypertensive treatment was discontinued after the procedure but was subsequently resumed if hypertension persisted. Secondary end points were the treatment score and the incidence of complications. Two patients in the control group and 6 in the angioplasty group suffered procedural complications (relative risk, 3.4; 95% confidence interval, 0.8 to 15.1). Early termination was required for refractory hypertension in 7 patients in the control group. Antihypertensive treatment was resumed in 17 patients in the angioplasty group. Mean ambulatory blood pressure at termination did not differ between control (141+/-15/84+/-11 mm Hg) and angioplasty (140+/-15/81+/-9 mm Hg) groups. Angioplasty reduced by 60% the probability of having a treatment score of 2 or more at termination (relative risk, 0.4; 95% confidence interval, 0.2 to 0.7). There was 1 case of dissection with segmental renal infarction and 3 of restenosis in the angioplasty group. No patient suffered renal artery thrombosis. In unilateral atherosclerotic renal artery stenosis, angioplasty is a drug-sparing procedure that involves some morbidity. Previous uncontrolled and unblinded assessments of angioplasty overestimated its potential for lowering blood pressure.     

Acute arterial hypertension caused by dissecting aneurysm of the renal artery

BACKGROUND: Aneurysm of the renal artery is an uncommon discovery at arteriography performed as part of a hypertension work-up. CASE REPORTS: We observed acute hypertension following dissection of a renal artery aneurysm which led to circulating channel stenosis. After surgical correction of the lesion, arterial pressures returned to normal. DISCUSSION: Most cases of renal artery aneurysm do not cause hypertension. In such cases, the high blood pressure is idiopathic or related to fibrodysplastic stenosis of the renal artery often associated with aneurysm formation. In rare cases with obstructive complications alone an aneurysm may lead to acute hypertension either after dissection as in our case or after thrombus formation. Surgery is generally required.     

Pulsus alternans in diastolic left ventricular dysfunction--a case report

Pulsus alternans is usually found in patients with reduced systolic ventricular function. We describe a patient with recurrent pulmonary edema, hypertension, bilateral renal artery stenosis, but with normal systolic function. Pulsus alternans was demonstrated in both pulmonary artery, right ventricle, and left ventricle pressures. After successful renal artery revascularization, the pulsus alternans disappeared. This case illustrates that pulsus alternans can be present with diastolic dysfunction of the left ventricle in the absence of systolic dysfunction.     

Renovascular hypertension: anatomic and renal function changes during drug therapy

Serial renal function studies were performed on 41 patients wtih renovascular hypertension (RVH) secondary to atherosclerotic renal artery disease who had been randomly selected for nonoperative management. In 19 patients, serum creatinine levels increased between 25% and 120%. The glomerular filtration rates dropped between 25% and 50% in 12 patients. Fourteen patients (37%) lost more than 10% of renal length. In four patients (12%), a significant stenosis progressed to total occlusion. Seventeen patients (41%) had deterioration of renal function or loss of renal size that led to operation. One patient required removal of a previously reconstructible kidney. Of the 17 patients with deterioration, 15 had acceptable blood pressure (BP) control during the period of nonoperative observation. Progressive deterioration of renal function in nonoperatively treated patients with atherosclerotic renal artery stenosis and RVH is common, and occurs even in the presence of BP control with drugs.     

Persistent increase in dopamine release following activation of metabotropic glutamate receptors in the rat nucleus accumbens

We report two cases of severe hypertension and unilateral renal dysplasia. No renal artery stenosis and no other urogenital malformations were found. In both cases we found substantially enhanced secretion of renin from the dysplastic kidney. After nephrectomy both patients obtained a distinctive and permanent reduction or normalization of blood pressure. In the two cases reported, regional renin release induced by ischemia is a very likely etiological factor.     

The molecular biology of chitin digestion

A beneficial effect in blood pressure control is presumed for patients on an intensive preoperative antihypertensive regimen who undergo empiric renal revascularization. Nonetheless, a noticeable decline in surgical cure rates for hypertension has been recently observed in patients with generalized atherosclerosis. The outcome of patients on multiple preoperative antihypertensive agents who underwent combined aortic and renal artery reconstruction was reviewed. The study population comprised 43 patients who underwent concomitant renal artery and aortic reconstruction for atherosclerotic disease between 1983 and 1995 and who were taking two or more antihypertensive medications and had a serum creatinine of less than or equal to 1.7 mg/dL. Operative management included an aortic reconstruction with either unilateral (n = 22) or bilateral (n = 19) aortorenal bypass or renal endarterectomy (n = 2). Operative mortality was 4.7% (2 of 43). The estimated 5-yr probability of survival was 83% (95% C.I. 0.70, 0.99). Late follow-up data on blood pressure control were available for review in 32 patients at a median follow-up of 37 months. Hypertension was cured in 1 (3%) and improved in an additional 15 (47%) patients. The numbers of antihypertensive medications taken preoperatively (mean = 2.7) declined at late follow-up (mean = 1.6). Notably, the largest reduction was observed with beta blockers (p = 0.006), central sympatholytics (p = 0.041), and angiotensin converting enzyme (ACE) inhibitors (p = 0.052). The number of preoperative antihypertensive medications was not significantly related to survival or to blood pressure improvement. However, uncontrolled preoperative hypertension despite antihypertensive therapy was associated with a favorable blood pressure response to operation (p < 0.001). Patients on an intensive antihypertensive regimen can safely undergo concomitant renal artery and aortic reconstruction for the empiric management of hypertension. Poorly controlled preoperative hypertension in the presence of multiple antihypertensive agents is a favorable marker for improved postoperative blood pressure control.