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.     

Long-term outcome after surgical kidney revascularization for fibromuscular dysplasia and atherosclerotic renal artery stenosis

PURPOSE: At a time of minimally invasive surgery in urology, the role of surgical kidney revascularization in the management of renal artery disease has changed during the last decade. Our experience with surgical kidney revascularization, and the long-term clinical outcomes of fibromuscular dysplasia (FMD) and atherosclerotic renal artery stenosis are reviewed. MATERIALS AND METHODS: The study group comprised 140 patients with renovascular hypertension, 72 with FMD and 68 with atherosclerotic renal artery disease, who underwent surgical revascularization between 1982 and 1999. The indications for surgical revascularization were the treatment of hypertension and the preservation of renal function in 17 patients with renal artery occlusion, 55 with ostial stenosis, 52 with branch stenosis, 6 with bilateral artery stenosis, 7 with solitary kidney renal artery stenosis and 3 with solitary kidney renal artery occlusion. RESULTS: Postoperative blood pressure and renal function were monitored for 1 to 17 years (mean 11.3). Long-term blood pressure control was observed in 93% of patients with FMD and in 71% of those with atherosclerosis. Improvement or stabilization of renal function was observed in 92% of patients with FMD and in 68% of those with atherosclerosis. The preoperative estimated glomerular filtration rate compared to postoperative was significantly increased in both groups. CONCLUSIONS: Surgical kidney revascularization is effective in secondary hypertension with a high long-term efficacy in the normalization of blood pressure and in the preservation of renal function, especially in patients with a solitary or 1 functional kidney.     

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.     

Randomized trials in angioplasty and stenting of the renal artery: tabular review of the literature and critical analysis of their results

As the incidence of hypertension (HTN) continues to rise, finding the optimal treatment of this multifactorial disease is critical. Renal artery stenosis (RAS) is a known etiology for HTN and is associated with declining renal function. Other than medications, the original gold standard for treatment of HTN from RAS was with an open surgical revascularization or nephrectomy. Since then, endovascular interventions for RAS have been reported to be technically possible, but their efficacy over medications or surgery has yielded conflicting results in case series and randomized trials. This tabular review summarizes the results of randomized trials that compared the outcomes of endovascular renal artery interventions with nonendovascular techniques (including medical and surgical treatments) for the treatment of HTN and renal dysfunction. Based on these data, the strengths and weaknesses of individual trials are critically analyzed to better define the methods to identify and treat patients with RAS.     

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.     

Renovascular hypertension

Renovascular hypertension is the most common cause of secondary hypertension. Interest in identifying patients with renal artery stenosis has been stimulated recently by advances in three areas. First, is the realization that not only can renal artery stenosis cause renovascular hypertension, but it can also lead to progressive renal failure (ischemic nephropathy) caused by progression of disease, usually atherosclerotic in nature. Second, advances in percutaneous transluminal renal angioplasty and, especially, the recent use of renal stents has led to a less invasive management of these patients as compared with traditional renal revascularization. Finally, the development of newer less invasive diagnostic techniques, both for the identification of patients with renal artery stenosis and to follow patients with known renal artery stenosis, has simplified the diagnostic aspect of the disease.     

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.     

The natural history of atherosclerotic and fibrous renal artery disease

Summary Individuals with atherosclerotic or fibrous renal artery disease may develop renovascular hypertension and/or renal dysfunction. Traditionally, the motivation for identifying patients with renal artery stenosis was the treatment of renovascular hypertension. However, recent interest has centered on the investigation of patients suspected of having renal artery stenosis that might account for progressive azotemia. While specific forms of fibrous and/or atherosclerotic renal artery disease can lead to a compromise in renal function, differences may exist in the age of presentation, predominat sex, angiographic appearance and overal natural history. Recognition of these differences is helpful in deciding on the most likely lesion type, appropriate workup and treatment. Since renal artery stenosis can lead to radiologic and functional alterations, clinical markers of progression, such as renal size and serum creatinine measurements, are helpful in identifying patients with advancing disease. The regulators of fibrous disease progression are less clear than those responsible for atherosclerotic progression in the renal artery. Uncontrolled systemic hypertension, intrarenal hypertension, hyperlipidemia, cigarette smoking, and obesity all may potentially contribute to progressive atherosclerosis. Individuals identified with progressive azotemia due to renal artery stenosis may benefit from improved perfusion flow by renal revascularization or balloon angioplasty provided no significant parenchymal disease is present.     

Two cases of atherosclerotic renal artery stenosis treated by percutaneous transluminal renal angioplasty and intravascular stent placement, leading to improvement of hypertension and renal function

We describe here two cases of renal artery stenosis(RAS) caused by atherosclerosis. Both patients were treated by percutaneous transluminal renal angioplasty(PTRA) and stent placement, leading to the improvement of renal function as well as hypertension. The two patients were a 75-year-old male(case 1) and a 56-year-old male(case 2), who both showed mild proteinuria, renal dysfunction, and refractory hypertension. Case 1 showed a unilateral ostial stenosis in the left main renal artery. On the other hand, case 2 showed an ostial stenosis in the left renal artery and a widespread narrowing in the right renal artery. After evaluation of the lesions by renal Doppler sonography, renogram, magnetic resonance signal intensity, and magnetic resonance angiography(MRA), each stenosis was treated by balloon angioplasty and intravascular stent placement without any major complications. Thereafter, in addition to hypertension, renal function also ameliorated significantly, and has remained stable for more than 12 months. Non-invasive screening tests and appropriate therapy for renovascular lesion should be considered in the case of elderly patients with refractory hypertension and progressive renal dysfunction, since ischemic nephropathy is increasing as a common cause of end stage renal disease and is showing favorable outcomes of revascularization.     

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.     

Trends in reconstruction for atherosclerotic renal vascular disease

Twenty-eight patients underwent renal vascular reconstruction for atherosclerotic renal vascular stenosis. Ten patients had therapeutic renal artery reconstruction for isolated renal artery stenosis causing severe hypertension, nine patients had therapeutic renal artery reconstruction for severe hypertension combined with simultaneous aortic reconstruction, and nine patients had prophylactic renal artery reconstruction for renal artery stenosis combined with simultaneous aortic reconstruction. Ninety percent of patients undergoing therapeutic renal revascularization procedures for hypertension were cured or improved. The 10 patients undergoing prophylactic renal artery reconstruction combined with aortic reconstruction had an average 72 percent reduction in the diameter of the vessel. Dacron side grafts sutured to the aortic graft were used for revascularization in each of the patients with prophylactic revascularization and was found to be an expedient means of reconstruction with good patency rates. No increased morbidity or mortality rate was noted in the prophylactic group. We believe that prophylactic revascularization should be carried out in patients with atherosclerotic high-grade stenosis of the renal arteries to prevent hypertension and preserve renal function.     

Angioplasty of the renal artery: antihypertensive and renal effects

Percutaneous transluminal angioplasty of the renal artery (PTRA) has been increasingly used over the past 20 years for treating renovascular hypertension (RVH). From the experience gathered so far it is justified to state that this technique is the first choice for patients with fibromuscular renal artery stenosis (RAS) because their cure rate is 50% and 42% improve. In contrast in patients with atherosclerotic RAS the cure rate after PTRA is 8-10% although 40-50% still improve. Since PTRA is associated with a 23% rate of major/minor complications and 30% restenosis (23% requiring stent implantation), it is obvious that in patients with atherosclerotic RAS the decision to attempt this procedure must be taken after careful selection of those who may actually benefit from the dilation. PTRA can be used more extensively for salvaging the function of the ischemic kidney than for treating hypertension because of the progressive nature of the atherosclerotic RAS and the lack of effective agents against such progression. After PTRA 35% of patients have some improvement in renal function and another 35% are stabilized. Yet most studies addressing the renal effects of PTRA suffer the limitation of having used serum creatinine levels as an indicator of glomerular filtration rate (GFR). More recent studies which used radioisotopic techniques to evaluate the changes of GFR induced by PTRA in the stenotic kidney indicate that after a successful procedure the increase is, on average, 8-10 ml/min. Interestingly it appears that this improvement is slower in kidneys of patients with atherosclerotic RAS than in those with fibromuscular RAS.     

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.     

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.     

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.     

Atherosclerotic renovascular disease: diagnosis and treatment

The technical expertise and tools required to treat renovascular obstruction have become commonplace, and many series of patients revascularized with surgery, balloon angioplasty or endovascular stenting have been reported. Nevertheless, although hypertension and renal failure are easy to diagnose, their cause often remains elusive. Evidence is developing that patients with hypertension and atherosclerotic renal artery stenosis may often have hypertension and renovascular disease but not hypertension because of renovascular disease. As a result, diagnosis and therapy are increasingly directed towards the preservation of renal function, and the future of renal revascularization will depend on how well potential therapies address this goal.     

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.     

Experience with percutaneous transluminal angioplasty for renal artery stenosis at the Cleveland Clinic

From April 1979 to June 1985 percutaneous transluminal angioplasty was attempted in 68 patients at our clinic to treat renovascular hypertension and/or to preserve renal function. The etiology of renal artery disease was atherosclerosis in 55 patients, fibrous dysplasia in 6, renal transplant arterial stenosis in 5 and postoperative saphenous vein graft stenosis in 2. A successful clinical outcome, defined as a decrease in blood pressure and/or improvement in renal function, was achieved in 12 patients (26.1 per cent) with atherosclerotic renal artery disease, 3 (75 per cent) with fibrous dysplasia, 2 (100 per cent) with saphenous vein graft stenosis and all 5 with transplant renal arterial stenosis (100 per cent). Improved results were observed in patients with nonostial atherosclerotic lesions compared to ostial lesions. There were 23 complications (33.8 per cent) after percutaneous transluminal angioplasty and all but 1 occurred with atherosclerosis. Of these complications 13 (19 per cent) were considered major. Since the beginning of 1983, however, only 3 complications occurred among 32 procedures (9.4 per cent) and only 1 of these was of major significance. When technically feasible, percutaneous transluminal angioplasty can provide effective treatment for selected patients with renal artery stenosis.     

Renovascular disease: effect of ACE gene deletion polymorphism and endovascular revascularization

BACKGROUND: Renal artery stenosis (RAS) is associated with high cardiovascular mortality and significant clinical complications, including resistant hypertension and ischemic nephropathy. Despite availability of endovascular revascularization techniques, determining which patients should undergo revascularization and the timing of the procedure still are controversial. Several studies have reported a higher frequency of the DD genotype of the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene in patients with RAS, and one study found higher mortality in patients with the DD genotype.Material and methods We retrospectively studied 100 patients with documented atherosclerotic RAS and evaluated long-term (median follow-up, 28 months) mortality, blood pressure control, and renal function in relation to the ACE genotype and two therapeutic strategies, that is, endovascular treatment with percutaneous renal transluminal angioplasty or stenting (ET group) versus conservative drug therapy (CT group). RESULTS: Comparison between therapeutic groups showed a higher cumulative probability of survival (86.7% vs 67.1%), better blood pressure control (57.4% vs 29%), and slower decline in renal function (17.9% vs 48.4%) in the ET group. The DD genotype was strongly represented in our study patients (DD, 50%; II, 15.5%; I/D, 34.5%), but bore no relation to mortality, blood pressure control, decline in renal function, or rate of recurrent stenosis. CONCLUSIONS: Conservative medical treatment of RAS, compared with endovascular treatment, is associated with higher mortality, poorer blood pressure control, and impaired renal function over the long term. Early endovascular treatment enables amelioration of this unfavorable evolution. The DD genotype does not predict clinical outcome of RAS.     

Renovascular hypertension. 8 years experience of a vascular surgery centre

AIM: The aim of this study was to evaluate the technical success and clinical outcome of surgical revascularization, angioplasty and/or stenting for renal artery stenosis (RAS) in patients with renovascular hypertension (RVH). The secondary aim was to identify independent negative predictors of blood pressure control after successful renal revascularization. METHODS: From January 1998 to July 2006, we treated 97 cases of RAS in 83 RVH patients. Inclusion criteria were RAS > or =80% associated with hypertension refractory to medical control with at least three drugs including a diuretic. Therapeutic options were surgical revascularization in 15 cases (11 renal endarterectomies, 4 aortorenal bypasses) and endoluminal treatment in 82 (14 balloon angioplasties, 68 stents). RESULTS: Technical success was 100% for both surgical and endovascular procedures; 13 cases of restenosis (> or =80%) were detected: 12 (14.6%) in the endoluminal group and one (6.6%) in the surgical group (P=0.68). During the follow-up period (average 37 months, range 6-94), blood pressure control improved in 43% of patients, disease stabilized in 37% and the natural course of RVH deteriorated in 20%. Multivariate Cox regression analysis showed that only a long history of antihypertensive drug use was a predictor of inefficacy of blood pressure control after revascularization (P<0.04). CONCLUSION: The complete resolution of RVH associated with severe RAS appears unrealistic in several cases. Early and long-term results in terms of technical success and restenosis were acceptable and similar for surgical and endovascular renal intervention. An early diagnosis of RVH could improve the control of hypertension after successful renal revascularization.