Epidemiology and clinical presentation

Renovascular disease appears to be increasing in prevalence, particularly in older subjects with atherosclerotic disease elsewhere. Its clinical manifestations and presentation are changing because of rapid advances in medical therapy and other comorbid events. Although fibromuscular dysplasia and other diseases affecting the renal artery can produce the syndrome of renovascular hypertension, atherosclerotic renal artery stenosis is the most common clinical entity. It can produce a spectrum of manifestations, ranging from asymptomatic ("incidental"), identified during angiographic evaluation of other conditions, to progressive hypertension to accelerated cardiovascular disease with pulmonary edema and advanced renal failure. With the widespread application of drugs which block the renin-angiotensin system, including angiotensin-converting enzyme inhibitors and angiotensin antagonists, many cases of renovascular hypertension remain unsuspected and never produce adverse effects. Clinicians need to be alert to the potential for disease progression, with the potential for total renal artery occlusion and/or loss of viable renal tissue. Selection of patients for renal revascularization depends on individual balance of risks and benefits regarding the likely outcomes regarding both improvements in blood pressure control and preservation of renal function.     

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.     

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.     

Revascularization for atherosclerotic renal artery stenosis: the treatment of choice?

Atherosclerotic renal artery stenosis (ARAS) is an important cause of renal dysfunction and secondary hypertension, and is associated with adverse cardiovascular events and increased mortality. The natural history of ARAS is characterized by anatomic disease progression and/or renal dysfunction in only a minority of patients. Medical therapy for ARAS is directed primarily toward blood pressure control and cardiovascular risk factor reduction. Renal artery revascularization is an additional treatment option for ARAS associated with ischemic nephropathy or severe, poorly controlled hypertension despite aggressive medical therapy. Unfortunately, the benefits associated with revascularization versus medical therapy alone remain unproven. Renal artery revascularization may be accomplished through open surgical revascularization or angioplasty and stenting. Although surgical renal revascularization is associated with more durable results and relatively lower risk for postoperative renal function decline, the increased risk of death or major complications associated with this management approach limit its use in patients with significant comorbidities. Renal artery angioplasty and stenting is being utilized with increasing frequency but is of uncertain benefit and is associated with rates of post-intervention renal function improvement and deterioration that are approximately equal. Renal function outcomes associated with angioplasty and stenting may be improved through a selective treatment approach and utilization of distal embolic protection. Renal artery revascularization represents the only treatment alternative for patients unresponsive to medical management, and is therefore the 'treatment of choice' in this select group. Results of ongoing randomized trials are eagerly anticipated and may provide useful guidance for future management of ARAS.     

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.     

The management of atherosclerotic renovascular disease

Atherosclerotic renovascular disease (ARVD) seems to be a common clinical condition. ARVD is clinically presented as: 'silent' renal artery stenosis, renovascular hypertension, ischemic nephropathy leading to deterioration of renal function and recurrent 'flash' pulmonary edema. Management of ARVD involves both revascularization and medical treatment. However, the impact of revascularization on kidney function and blood pressure control is a matter of great controversy in view of the results of recent randomized clinical trials. At present, concerted medical management (includes lifestyle modifications, such as smoking cessation) remains the main treatment option for patients with ARVD. However, there is a need to accurately identify individuals who may benefit from renal revascularization.     

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.     

Pathogenesis and management of renovascular hypertension and ischemic nephropathy

Renovascular disease is an important cause of secondary hypertension and renal impairment. Atherosclerotic renal artery stenosis (ARAS) is the most important cause of renal artery stenosis (RAS), and has been linked to increased cardiovascular risk. The pathogenesis of renovascular hypertension is complex, but is mainly due to the over-activation of Renin-Angiotensin-Aldosterone system. A major consequence of untreated RAS is ischemic nephropathy, which is due to the sustained reduction in renal perfusion leading to derangement of microvascular function, and eventual development of interstitial fibrosis. Diagnosis of these conditions can be complex, sometimes needing invasive testing. Aggressive medical management is key to preventing progression of disease, as the role of revascularization in the management of ARAS is still not well defined.     

Ischemic nephropathy/azotemic renovascular disease

Atherosclerotic renal vascular disease can impair kidney perfusion and lead to deterioration of kidney function. The mechanisms by which reversible tissue injury becomes irreversible are not yet certain, although multiple pathways for activation of inflammatory cytokines and tissue fibrosis have been identified. The clinical hallmark of this disorder is loss of glomerular filtration beyond renal artery stenosis affecting the entire renal mass, usually associated with progressive hypertension and fluid retention. Some investigators believe that 12% to 18% of patients reaching end-stage renal disease in western countries may have lost kidney function because of azotemic renovascular disease. This is an important disorder to identify, because reduction of arterial pressure from antihypertensive therapy may further reduce kidney perfusion. Although administration of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists lead to functional loss of glomerular filtration rate (GFR) beyond a stenotic lesion because of the removal of efferent actions of angiotensin II, other antihypertensive agents reduce renal perfusion also. Restoration of renal blood flow by surgical or endovascular methods can prevent progressive disease and sometimes improves renal function. However, clinical series commonly indicate that some patients lose further kidney function after revascularization. This may be explained partly by undetected renal atheremboli or other toxicity related to vascular repair. Hence, selection of patients for renal revascularization requires careful consideration of comorbid disease risk and the balance of risks and benefits regarding progressive renal disease. Searching for better methods of identifying those individuals at risk for irreversible loss of renal function and who might benefit from vascular repair is a high research priority.     

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.     

Advances in the medical management of renovascular hypertension

Although clinical reports have suggested that antihypertensive therapy can control blood pressure in patients with renovascular hypertension, adequate randomized studies comparing medical versus surgical management are lacking. It is well recognized that progressive deterioration in renal function can occur despite good blood pressure control. Recent experience suggests that higher-risk patients with atherosclerotic renovascular hypertension can benefit from an aggressive surgical approach, whereas newer medical therapies capable of specific inhibition of the renin-angiotensin system suggest greater potential benefits to other patients. Properly performed randomized trials comparing medical versus surgical therapy of renovascular hypertension are needed.     

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.     

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.     

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.     

Clinical trials in nephrology: success or failure

PURPOSE OF REVIEW: A large amount of clinical and epidemiologic evidence has been gathered supporting the importance of blood pressure control in reducing chronic kidney disease progression. Suppression of the rennin-angiotensin-aldosterone system should also be considered in any patient with chronic kidney disease, in particular if albuminuria is present. RECENT FINDINGS: Analysis of renal outcome by estimating glomerular filtration rate in trials primarily devoted to cardiovascular protection in hypertensive patients, in particular the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial trial, has come to question the effectiveness of suppressing the rennin-angiotensin-aldosterone system in controlling blood pressure and thus protecting the kidney in hypertensive patients. This subject is particularly interesting because the existence of an increased cardiovascular risk associated with renal function decline has been demonstrated in many different clinical conditions including arterial hypertension. The increase in global cardiovascular risk accompanying chronic kidney disease would necessitate the use of drugs suppressing the rennin-angiotensin-aldosterone system for cardiovascular protection irrespective of the influence on renal outcome. SUMMARY: This review includes the most recent data evaluating renal endpoints in clinical trials primarily devoted to renal function as well as those dedicated to arterial hypertension and its cardiovascular consequences.     

Renovascular hypertension

Renal artery stenosis is one of the most important forms of secondary hypertension. For years, the only causative treatment was nephrectomy. With rapid advances in cardiovascular and transplantation surgery, operative procedures in renovascular hypertension become more and more sophisticated. Revascularization is superior to medical management of renovascular hypertension in terms of preserved renal function. In recent years, surgical result have been excellent, and even patients with rather complex forms of renovascular hypertension have been successfully operated upon. New classes of antihypertensive drugs, particularly beta-blockers and angiotensin I converting enzyme inhibitors, have enabled the control of blood pressure in most patients with renovascular hypertension but do not assure preservation of renal function. Finally, a fascinating technique, the percutaneous transluminal renal angioplasty, has rapidly advanced to become one of the most popular methods in the treatment of hypertension secondary to renal artery stenosis. However, percutaneous transluminal renal angioplasty is the treatment of choice for most nonostial, nonocclusive lesions.     

Vasculo-renal disease

The kidney as an apo-exocrine organ has two important functions: the control of homeostasis and arterial blood pressure. Any pathological disorders witch alters the renal blood flow results in two consequences: renovascular hypertension and renal insufficiency. Renal revascularization looks for with priority the improvement of renal function; the good response and control of hypertension shall come after. The goals of this paper is to actualize the sophisticated diagnostic methods (Angiography, Eco-Doppler, AngioCT, AngioMR, Angioscopy; and the use of contrast potential-mediums), functionality tests (RN and MR with Captopril) and management (Percutaneous transluminal angioplasty, simple or covered Stents, Embolizations, Occlusive balloons, Fibrinolysis and Trombus Aspiration; direct Arterial Surgery and renal Autotransplantation) of different renovascular diseases. (Blunt renal injuries, Stenosis, Aneurysms. A-V fistuls, Acute Occlusions or arterial and venous, Thrombosis. Nutcraker Syndrome). The possibility of the presence of an inverse venous Fraley's Syndrome is presented and discussed. CONCLUSIONS: A controversy of the last technical methods are established and discussed and a Guideline is recommended for each renal vascular disease.     

Medical management of renovascular hypertension

Summary The preferred treatment for renovascular hypertension is revascularization of the ischemic kidney, which helps to preserve renal function as well as lower blood pressure. Medical management plays an important role, however, both as initial therapy for patients who are undergoing revascularization and as maintenance therapy when this cannot be undertaken or has been unsuccessful. The relative merits of the different types of treatment depend on a variety of factors such as the age of the patient, the etiology of the renal artery stenosis, and the presence or absence of concomitant disease.     

Renovascular operations in patients with chronic renal insufficiency: do the benefits justify the risks?

To define the benefits and risks of renal revascularization or nephrectomy in patients with both severe hypertension and chronic renal insufficiency, we analyzed 98 patients who underwent renovascular operations after serum creatinine levels exceeded 2 mg/dl. This subset of patients was selected from a retrospective review of 652 renal operations performed at the Mayo Clinic for renovascular disease between 1970 and 1981. Special attention was given to the type of operations, their effect on hypertension and renal function, specific factors that affected operative deaths, and late survival. Unilateral renal operations were performed in 48 patients with bilateral procedures in 50. Simultaneous aortic reconstruction was necessary in 55 patients (56%). Postoperative diastolic blood pressure was less than 90 mm Hg in 55% of patients and 90 to 100 mm Hg in an additional 33%. Seventy-six percent of patients required less antihypertension medication. Serum creatinine improved or stabilized in 69%. Ninety percent of patients avoided any early or late renal dialysis. The operative mortality rate was 7.1% and tended to be higher in patients with a serum creatinine greater than 3 mg/dl and in those with past myocardial infarction (p = 0.05). The late survival rate was 64% at 5 years. The main cause of operative and late death was myocardial infarction. In conclusion, most patients with renovascular hypertension and early chronic renal insufficiency can be benefited by surgical revascularization or nephrectomy. Future improvement in early and late survival may require a more aggressive approach to the identification and correction of significant coronary artery disease.     

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.