Long-term follow-up of atherosclerotic renovascular disease. Beneficial effect of ACE inhibition.

BACKGROUND: Patients with atherosclerotic renovascular disease (ARVD) are almost invariably treated by revascularization. However, the long-term outcomes of this approach on survival and progression to renal failure have not been investigated and have not been compared with that of a purely medical treatment. The aim of this observational study was to investigate factors affecting long-term (over 5 years) outcome, survival and renal function of patients with ARVD treated invasively or medically. METHODS: ARVD was demonstrated angiographically in 195 patients who were consecutively enrolled into a follow-up study. Patient age was 65.6+/-11.2 years, serum creatinine was 1.74+/-1.22 mg/dl and renal artery lumen narrowing was 73.5+/-17.5%. A revascularization was performed in 136 patients, whereas 54 subjects having comparable characteristics were maintained on a medical treatment throughout the study; five patients were lost during follow-up. RESULTS: The main follow-up was 54.4+/-40.4 months. The assessment of cardiovascular survival and renal survival at the end of follow-up revealed 46 cardiovascular deaths, 20 patients with end-stage renal disease (ESRD) and 41 patients with an increase in serum creatinine of over one-third. The multivariate analysis showed that renal revascularization did not affect mortality or renal survival compared with medical treatment. Revascularization produced slightly lower increases in serum creatinine and a better control of blood pressure. A longer survival was associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) (P = 0.002) in both revascularized and medically treated patients. The only significant predictor of ESRD was an abnormal baseline serum creatinine. CONCLUSIONS: On long-term follow-up, ARVD was associated with a poor prognosis due to a high cardiovascular mortality and a high rate of ESRD. In our non-randomized study, revascularization was not a major advantage over medical treatment in terms of mortality or renal survival. The use of ACEIs was associated with improved survival.     

Evidence-based medicine in renal artery stenting

Atherosclerotic renovascular disease is an increasingly recognized cause of severe hypertension and declining kidney function. Patients with atherosclerotic renovascular disease have been demonstrated to have an increased risk of adverse cardiovascular events. Over the course of the last two decades renal artery revascularization for treatment of atherosclerotic renal artery stenosis (RAS) has gained great increase via percutaneous techniques. However the efficacy of contemporary revascularization therapies in the treatment of renal artery stenosis is unproven and controversial. The indication for renal artery stenting is widely questioned due to a not yet proven benefit of renal revascularization compared to best medical therapy. Many authors question the efficacy of percutaneous renal revascularization on clinical outcome parameters, such as preservation of renal function and blood pressure control. None of the so far published randomized controlled trials could prove a beneficial outcome of RAS revascularization compared with medical management. Currently accepted indications for revascularization are significant RAS with progressive or acute deterioration of renal function and/or severe uncontrollable hypertension, renal function decline with the use of agents blocking the renin-angiotensin system and recurrent flash pulmonary edema. The key point for success is the correct selection of the patient. This article summarizes the background and the limitations of the so far published and still ongoing controlled trials.     

Treatment of renovascular disease and of renovascular hypertension

ABSTRACT: Treatment of occlusive lesions of renal arteries, defined as renovascular disease (RVD), is aimed both at preventing ischemic renal disease (IRD) and rescuing renal function through revascularization procedures, such as PTRA, endovascular stenting and surgical revascularization, as well as curing or improving hypertension in the presence of renovascular hypertension (RVH), i.e. hypertension caused by these vascular lesions. Preventive treatment of IRD is still an individual decision making process based on the type of renal lesions, degree of renal stenosis and progressive loss of renal mass as well as on immediate and late technical success of revascularization procedures together with their rate of complications. Rescue of renal function and-or prediction of the outcome of renal function after successful revascularization depends not only on the possibility of clarifying whether the decrease in renal function is a functioning-reversible phenomenon linked to renal hypoperfusion but also on the potential risk that the revascularization procedure may induce irreversible kidney damage. The rationale for treating RVH through revascularization procedures derives from the possibility of establishing a pathogenetic link between the occlusive lesions and hypertension, mainly through renal vein renin measurement and captopril renography and possibly their combination. Finally, medical treatment of hypertension is needed in patients who cannot undergo or refuse revascularization and whose blood pressure is not normalized by these procedures.     

Revascularization in atherosclerotic renovascular disease: problems beyond the obstruction

The main goal in the treatment of obstructive atherosclerotic renovascular disease (ARVD) is to preserve or recover renal function. The ARVD kidney continues to deteriorate in 20-40% of cases despite restoration of blood flow. Holden et al. report that renal function stabilized or improved in up to 97% of patients with the use of a distal embolic protection device.     

Evaluation and preparation for surgical treatment of renal artery disease

The diagnosis of renovascular disease and renovascular hypertension is outlined. A comparison and analysis of the advantages of three forms of treatment are made. These include medical management, percutaneous transluminal coronary angioplasty, and surgical intervention. Selection of patients for revascularization to preserve renal function is discussed, and guidelines for determining renal salvageability are presented. Surgical revascularization is the treatment of choice for patients with ostial atherosclerotic renal artery disease, branch renal artery disease, or a renal artery aneurysm.     

Magnetic resonance imaging: advances in the investigation of atheromatous renovascular disease

Prediction of renal functional outcome following revascularization procedures in atheromatous renovascular disease (ARVD) has remained a challenge. In considering the etiology of renal impairment, researchers have shifted their focus now from the influence of degree of renal artery stenosis (RAS) to the importance of intrinsic parenchymal damage caused by hypertension, atheroemboli, downstream cytokine and/or cholesterol crystal release, as well as indicators of tissue viability. Magnetic resonance (MR) imaging techniques and MR-based indices are able to provide a detailed assessment of the morphologic and functional aspects of the ARVD kidney. These indices look beyond "lumenology" and enable a better understanding of the parenchyma's physiology which may provide insight into predictors of outcome. This review summarizes the multipurpose benefits of MR in the assessment of ARVD.     

Predictive Factors and Therapeutic Approach of Renovascular Disease: Four Years’ Follow-Up

Background. There is no consensus about the renal function outcome after revascularization with stenting in atherosclerotic renovascular disease. In the present study, the outcome in BP control and renal function in patients with renovascular disease treated with percutaneous angioplasty and stent placement is compared with the outcome in patients with renovascular disease treated with medical treatment only. Additionally, the impact of oxidative stress and eosinophil count in peripheral blood as predictors of renal function deterioration in renovascular disease irrespective of treatment is investigated. Methods. Eighty-two patients with renovascular disease were enrolled into a follow-up study (47.5±35.4 months). Thirty-six patients (group 1) underwent revascularization and stenting, and 46 patients (group 2) were on medical treatment only. In all patients, serum creatinine concentration, eosinophil count (EO) in peripheral blood, and estimation of oxidative stress with dROMs test were determined before and at the end of the follow-up. Results. In revascularized patients (group 1), hypertension was cured in 11.1% and improved in 66.6%. Renal function improved in 30.5% and worsened in 36.2% of patients. In the medical treatment arm (group 2), hypertension improved in 71.4% of the patients. Renal function remained stable in 69.8% of patients and worsened in 30.2%. Cox regression analysis showed that higher levels of eosinophil count and higher levels of ROS, irrespectively of mode of treatment, were associated with renal function deterioration (i.e., serum creatinine increase more than 20% during follow-up). Conclusions. Revascularization was not superior to medical treatment in renal survival but had a greater positive impact on blood pressure control. Eosinophil count and oxidative stress were the stronger predictive factors for serum creatinine increase.     

Left ventricular morphology and function in patients with atherosclerotic renovascular disease

Atherosclerotic renovascular disease (ARVD) is associated with heart disease. There has been no systematic study of cardiac structure and function in patients with this condition. In this study, the epidemiology of cardiac changes and their relationship to renal function, renovascular anatomy, and BP are delineated. With the use of a cross-sectional design, 79 patients with ARVD and 50 control patients without ARVD underwent echocardiography and 24-h ambulatory BP monitoring. Clinical and biochemical data were collected. Results were analyzed according to renal function, residual renal artery patency, and unilateral or bilateral ARVD. Only 4 (5.1%) patients with ARVD had normal cardiac structure and function. Patients with ARVD (age 70.7 +/- 7.5 yr; estimated GFR 36 +/- 19 ml/min) had significantly more cardiovascular comorbidity (77.2 versus 42.0%; P < 0.001), greater prevalence of left ventricular (LV) hypertrophy (78.5 versus 46.0%; P < 0.001) and LV diastolic dysfunction (74.6 versus 40.0%; P < 0.001), and greater LV mass index (183 +/- 74 versus 116 +/- 33 g/m2; P < 0.001) and LV end-diastolic volume index (82 +/- 35 versus 34 +/- 16 ml/m2; P < 0.001) than control subjects. BP was similar for both patient groups. For patients with ARVD, neither renal function nor renal artery patency predicted a difference in echocardiographic or ambulatory BP monitoring parameters. Patients with bilateral ARVD had greater LV mass index and LV dilation than patients with unilateral disease. Patients with ARVD exhibit a high prevalence of cardiac morphologic and functional abnormalities at early stages of renal dysfunction. Such patients must be identified early in their disease course to allow risk factor modification.     

Relationship of renal dysfunction to proximal arterial disease severity in atherosclerotic renovascular disease.

BACKGROUND: Renal impairment is common in patients with atherosclerotic renovascular disease (ARVD), but its pathogenesis is uncertain. This study investigated whether any relationship existed between renal function and the severity of proximal renal arterial lesions in patients with ARVD. METHODS: A cohort of 71 patients had creatinine clearance measured at the time of digital subtraction angiography; eight patients were diabetics and were excluded from further analysis. The severity of proximal renovascular lesions was estimated by standard methodology, and patients were sub-grouped according to residual patency of the proximal renal arteries (e.g. normal=2.0; unilateral occlusion )RAO(=1.0). Renal bipolar lengths at ultrasound were also assessed. RESULTS: Sixty-three non-diabetic patients (mean+/-SD age 67.7+/-5.8 years; 34 males) were suitable for study. No differences in renal function (mean+/-SD creatinine clearance (ml/min)) were seen between patients with unilateral (32. 1+/-18.9, n=36) or bilateral (31.7+/-20.9, n=27) disease, or between sub-groups with RAS <60% (28.3+/-13.9, n=15), unilateral RAS >60% (38.9+/-24.6, n=12), bilateral RAS >60% (36.3+/-20.4, n=6) or unilateral RAO (30.3+/-17.7, n=28), and mean average renal size similarly did not differ between the sub-groups. No correlation existed between residual patency and creatinine clearance (r=0.015); mean+/-SD renal function was almost identical in the four patency sub-groups, and average renal size mirrored this pattern. Mean 24-h urinary protein excretion was similar for the four groups, but patients with minimal ARVD had significantly less comorbid vascular disease. CONCLUSIONS: These findings suggest that the severity of proximal renal artery lesions is often unrelated to the severity of renal dysfunction in patients with ARVD. Associated renal parenchymal damage is the more probable arbiter of renal dysfunction, and this should be considered when revascularization procedures are contemplated.     

The current status of surgical therapy for renal artery disease

The first reports of surgically curable hypertension in the late 1930s led to enthusiasm among clinicians for removing kidneys with arterial stenosis in hypertensive patients. The development of vascular surgical techniques in the 1950s made it possible to achieve successful renal revascularization in many of these cases. However, the cause and effect relationship between a stenotic renal artery lesion and hypertension was poorly understood and many patients treated surgically had no improvement of blood pressure postoperatively. Continued experience in this field during the past two decades has significantly improved our understanding of the natural history and functional significance of renovascular disorders. Patients with renovascular hypertension can now be identified with a high degree of accuracy and successful renal revascularization is possible in most cases. Nevertheless, multiple factors must be weighed in determining whether medical or surgical therapy is more appropriate for a given patient. These include the causal relationship of renovascular disease to hypertension, the adequacy of blood pressure control with medical therapy, the natural history of untreated renovascular disease with particular regard for the risk of sustaining impaired renal function, the medical condition of the patient, the morbidity and results of surgical therapy, and the availability of other therapeutic options such as percutaneous transluminal dilatation.     

Diagnostic criteria for renovascular disease: where are we now?

Renovascular disease, especially atherosclerotic renal artery stenosis (ARAS) in older subjects, is commonly encountered in clinical practice. This is at least in part due to the major advances in non-invasive imaging techniques that allow greater diagnostic sensitivity and accuracy than ever before. Despite increased awareness of ARAS, renal revascularization is less commonly performed, likely as a result of several prospective, randomized, clinical trials which fail to demonstrate major benefits of renal revascularization beyond medical therapy alone. Primary care physicians are less likely to investigate renovascular disease and nephrologists likely see more patients after a period of unsuccessful medical therapy with more advanced ARAS. The goal of this review is to revisit current diagnostic and therapeutic paradigms in order to characterize more clearly which patients will likely benefit from further evaluation and intensive treatment of renal artery stenosis.     

Renal artery stenosis and chronic ischemic nephropathy: epidemiology and diagnosis

Atherosclerotic renal artery stenosis (RAS) is the most common primary disease of the renal arteries and results in renovascular hypertension and ischemic nephropathy. Ischemic nephropathy from atherosclerotic RAS is increasingly recognized as a cause of chronic kidney disease (CKD) and in severe cases can lead to end-stage renal disease. The exact prevalence of atherosclerotic RAS is unknown because the disease is often asymptomatic and few are screened unless they have significant traditional cardiac risk factors or symptoms. A high prevalence of atherosclerotic RAS is seen in patients with advanced age, congestive heart failure, and extrarenal atherosclerosis. The primary reason for diagnosing ischemic nephropathy from renovascular disease is that the loss of kidney function is potentially reversible through treatment of the occlusion with surgical revascularization or percutaneous transluminal renal angioplasty. However, the benefits of revascularization have to be considered in the context of other comorbid disease and remain controversial. There are several tests available for the screening and diagnosis of atherosclerotic RAS; however, the diagnostic test of choice should be based on patient factors and institutional expertise because the best test is the one performed most often at the individual medical facility.     

Leitlinie zur chirurgischen Therapie bei Erkrankungen der Nierenarterien

Background

These guidelines are the current publication of the German guidelines for surgical revascularization of renal artery disease, focusing on atherosclerotic renal artery stenosis. These guidelines update a previous version: Allenberg JR (1998) Guidelines for renovascular disease. In: German College of Vascular Surgery (DGG) Guidelines for diagnostic and therapy in vascular surgery. Deutscher Ärzteverlag, Köln

Purpose

The aim was to evaluate the effect of surgical revascularization on clinical outcomes in adults with atherosclerotic renal artery stenosis in comparison to endovascular therapy or best medical treatment.

Data Sources

The appropriate criteria were reviewed by a literature search (MEDLINE database) and updated in order to evaluate the results of previous studies and obtain new and highly significant scientific evidence on the surgical therapy of renovascular diseases.

Data interpretation

Using the evidence-based criteria there were only two randomized trials with an evidence level type Ib, one comparing surgical revascularization with best medical treatment and another comparing surgical revascularization with percutaneous transluminal angioplasty (PTA). In both studies there were no significant differences in the outcome. However, the statistical power of these trials with a total of 110 randomized patients was poor. Many trials with evidence level II and III have been carried out. Available evidence is not sufficient to predict which intervention would result in better outcomes. There have been no randomized prospective trials comparing the three therapeutic options, surgical revascularization, PTA/stent and best medical treatment.

Conclusion

An advantage for a specific type of therapy has not yet been demonstrated. The decision for any kind of treatment approach depends on the individual renal artery lesion, the therapeutic options, skills and the necessary interdisciplinary infrastructure of the treating medical unit.     

Heart and renal failure in renovascular hypertension caused by giant cell arteritis--case report

We report a case of a male teenager with severe heart and acute renal failure as the dominant clinical manifestations of renovascular hypertension (RVH) caused by atypical giant cell arteritis (GCA). Unrecognized RVH and treatment of the consequent heart failure by angiotensin-converting enzyme inhibitors (ACEI) probably contributed to progression of renovascular disease to bilateral renal artery occlusion. Recurrent "flash" pulmonary edemas could not be prevented until surgical revascularization of the only functioning right kidney was achieved by an aortorenal bypass. Prompt post-operative normalization of heart function and arterial hypertension occurred despite the histopathological finding of the resected renal artery compatible with GCA and 4-year duration of significant renovascular disease. At the last check-up, the patient was asymptomatic, with normal arterial pressure on the prescribed treatment: carvedilol, hydrochlorothiazide, prednisolone 20 mg daily and aspirin. Subsequent follow-up is necessary to observe the evolution of GCA as an exceptionally rare cause of RVH.     

Continuing uncertainty about the value of percutaneous revascularization in atherosclerotic renovascular disease: a meta-analysis of randomized trials.

BACKGROUND:To study the effect of revascularization on blood pressure (BP) and serum creatinine (SCr) in patients with atherosclerotic renovascular disease (ARVD). METHODS:Three randomized studies comparing balloon angioplasty (plus medication if necessary) with medical therapy alone in patients with ARVD were identified. In one study, patients were stratified and analysed according to whether they had unilateral or bilateral disease. Therefore, four sets of results were available for inclusion in a meta-analysis comparing BP and SCr at 6 months and changes from baseline. RESULTS:The three trials recruited 210 patients. There was no clear benefit for angioplasty when comparing BP at 6 months. Relative to the medical therapy group, the mean (95% CI) systolic/diastolic BP was 2.9 mmHg (-9.1, 3.4)/0.35 mmHg (-3.6, 2.9) lower in the angioplasty group (P=0.4/0.8). There was, however, some suggestion of benefit for angioplasty when changes in BP were compared. There was a greater reduction in the systolic/diastolic BP in the angioplasty group, with a difference of 6.3 mmHg (-11.7, -0.8)/3.3 mmHg (-6.2, -0.4) in the mean change (P=0.02/0.03). There was some suggestion of benefit for angioplasty in terms of changes in SCr, although this was not significant (P=0.06). CONCLUSIONS:The reported trials have been too small to determine reliably the role of angioplasty in ARVD. Although the combined results of three previous trials exclude the possibility of a large improvement in renal function or hypertension after angioplasty, a moderate but clinically worthwhile benefit cannot be ruled out. Further large-scale randomized evidence is needed.     

Revascularization to preserve renal function in patients with atherosclerotic renovascular disease

There are a significant number of patients with advanced atherosclerotic renovascular disease whose blood pressure is well controlled with medical therapy but in whom such vascular disease poses a grave risk to overall renal function. This article reviews current concepts regarding screening, evaluation, and selection of patients with this disease for revascularization to preserve renal function. The underlying rationale for this approach is an increasing awareness that, in selected patients, atherosclerotic renovascular disease represents a surgically correctable cause of progressive renal failure.     

Atherosclerotic renovascular disease: medical therapy versus medical therapy plus renal artery stenting in preventing renal failure progression: the rationale and study design of a prospective, multicenter and randomized trial (NITER)

BACKGROUND: Many studies suggest a major prevalence of atherosclerotic renovascular disease (ARVD), caused by mono or bilateral renal artery stenosis (RAS). Unfortunately, there is no definite therapy to cure this disease to date; therefore, ARVD is burdened by important clinical complications with high social and economic costs. The last few years have seen important advancements in both medical therapy and in interventional radiology (for example, percutaneous transluminal renal artery stenting (PTRS)). All of them could affect, in some way, the natural history of ARVD, but to date the optimal strategy has not been established. METHODS: The protocol of a prospective, multicenter, randomized trial "Nephropathy Ischemic Therapy (NITER)" is presented. It enrolls patients with stable renal failure (glomerular filtration rate (GFR) >or=30 ml/min) and hypertension, and hemodynamically significant atherosclerotic ostial RAS (>or=70%) diagnosed by duplex Doppler (DD) ultrasonography and confirmed by magnetic resonance angiography (MRA). This study aims to evaluate whether medical therapy plus interventional PTRS is superior to medical therapy alone according to the following combined primary endpoint: death or dialysis initiation or reduction by >20% in estimated GFR after 0.5, 1, and 2 yrs of follow-up and an extended follow-up until the 4th year. Medical therapy means drugs to control hypertension, improve dyslipidemia and optimize platelet anti-aggregant therapy. The sample size is estimated in 50 patients per group to achieve a statistical significance of 0.05 in case of a reduction by 50% in the combined endpoints.     

Captopril renal scintigraphy--an advance in the detection and treatment of renovascular hypertension

Despite the risks associated with renovascular hypertension and the durable benefits of revascularization, the detection of patients with renovascular hypertension and the selection of those who will benefit from interventional therapy remains a challenge. We have previously documented the reliability of captopril renal scintigraphy in predicting angiographically significant renal artery stenosis in patients suspected of having renovascular hypertension. In the present study we report our recent experience with this noninvasive technique in predicting outcome after revascularization. Captopril renal scintigraphy involves the administration of 50 mg of captopril 3 hours after a baseline technitium-99m diethylenetriaminepentaacetic acid renal scan and 1 hour before a repeat captopril renal scintigraphy scan. Nineteen of the last 70 patients with clinically suspected renovascular hypertension undergoing captopril renal scintigraphy had abnormal renal scan outcomes, and 17 had a decrease in flow or function after captopril (positive captopril renal scintigraphy). Eight of these 17 with abnormal findings on captopril renal scintigraphy underwent revascularization, and the hypertension was cured or improved in six of the eight: two of three after surgical bypass grafting and four of five after angioplasty. In the seven surviving patients with abnormal renal scan results but no change with captopril (negative captopril renal scintigraphy), improvement in hypertension after treatment occurred in only one: one of two after nephrectomy, zero of three after bypass surgery, and zero of two after angioplasty (p less than 0.05). We conclude that captopril renal scintigraphy is an accurate predictor of hypertension response to revascularization. Further evaluation of this new noninvasive technique for assessing patients with suspected renovascular hypertension appears warranted.     

Improved results of vascular reconstruction in pediatric and young adult patients with renovascular hypertension

From 1955 to 1988, 56 patients 21 years old or younger underwent surgical treatment for renovascular hypertension at our clinic. The cause of renal artery disease was fibrous dysplasia in 53 patients, Takayasu's arteritis in 2 or an arterial aneurysm in 1. Bilateral or branch renal artery disease, and extrarenal arterial disease were present in 16, 23 and 11 patients, respectively. The results of 28 patients treated from 1955 to 1977 (group 1) were compared to those of 28 patients treated from 1978 to 1988 (group 2). Hypertension was cured or improved postoperatively in 83% of the patients from group 1 and in 96% from group 2 (p = 0.07). However, this outcome was achieved through surgical revascularization in only 48% of the patients from group 1 compared to 96% from group 2 (p = 0.0002). A multivariate analysis revealed that the only significant variable related to clinical outcome was the era of treatment, which reflects the improved technical efficacy of revascularization during the last decade. Aortorenal bypass and renal autotransplantation have emerged as the preferred revascularization operations. It currently is possible to achieve amelioration of hypertension and preservation of renal function in most young patients with renal artery disease.     

Ischemic nephropathy: where are we now?

Identification and reversing the loss of kidney function beyond occlusive disease of the renal arteries poses a major clinical challenge. Recent studies indicate that atherosclerotic renal artery stenosis develops as a function of age and is commonly associated with other microvascular disease, including nephrosclerosis and diabetic nephropathy. The risks of renal artery stenosis are related both to declining kidney function and to accelerated cardiovascular disease, with increased morbidity and mortality. Newer drugs, including agents that block the renin-angiotensin system, have improved the level of BP control for renovascular hypertension. Progressive renovascular disease during medical therapy can produce refractory hypertension, congestive heart failure, and renal failure with tubulointerstitial fibrosis. Recent studies indicate a complex interplay of oxidative stress, endothelial dysfunction, and activation of fibrogenic cytokines as a result of experimental atherosclerosis and renal hypoperfusion. Advances in imaging and interventional devices offer major new opportunities to prevent progressive loss of kidney function. Recent series indicate that although 25 to 30% of patients with impaired renal function can recover glomerular filtration after revascularization, many have no apparent change in kidney function and 19 to 25% experience a significant loss of kidney function, in some cases as a result of atheroemboli. To select patients who are most likely to benefit from vascular intervention, clinicians should understand the pathophysiology of developing ischemic nephropathy and the potential hazards of revascularization in the setting of diffuse atherosclerotic disease. Further research should be directed toward identification of critical disease, regulation of fibrogenesis, and the interaction with other atherosclerotic processes.