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.     

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.     

A review of the current treatment of renal artery stenosis.

PURPOSE: Atherosclerotic renal artery stenosis (ARAS) is associated with morbidity and mortality consequent to progressive ischemic renal failure and the cardiovascular consequences of hypertension. There is considerable uncertainty concerning the optimal management of patients with this condition. This review considers the aetiological factors and the physiologic consequences of ARAS and compares the results of clinical studies of medical and endovascular therapies on blood pressure control and preservation of renal function. RESULTS: Although, in patients with fibromuscular disease the results of percutaneous transluminal angioplasty (PTA) are clearly superior to medical therapy and surgery, in asymptomatic patients with ARAS the antihypertensive benefits and preservation of renal function of endovascular, surgical and medical therapies appear similar. In selected symptomatic patients interventions may, however, be life-saving. Surgery is generally reserved for arterial occlusions with preserved renal parenchyma and function. CONCLUSIONS: The results of larger, multicentre, randomised, controlled trials are required to clearly clarify the role of interventional therapy in asymptomatic patients.     

Renovascular hypertension: current concepts

Hypertension produced by renal artery occlusive disease is an important secondary form of hypertension. Clinicians commonly encounter forms of renal arterial disease of varying severity, many of which are of little hemodynamic significance when first detected. Experimental studies emphasize that transient activation of the renin-angiotensin-aldosterone system is necessary for initiation of renovascular hypertension. At some point, angiotensin II activates additional mechanisms responsible for sustained increased blood pressure including sodium retention, endothelial dysfunction, and vasoconstriction related to production of reactive oxygen species. Widespread application of agents that block the renin-angiotensin system, including angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, render many patients with unilateral renal arterial disease manageable primarily by medical means for many years. In the setting of high a priori likelihood of renovascular disease, recognizing the potential for disease progression during medical therapy and individually evaluating the risks and benefits of renal revascularization are important tasks. Recent prospective studies show limited, but real, benefit regarding blood pressure control for patients with atherosclerotic disease. Whether earlier renal revascularization offers benefits regarding improved morbidity and mortality from cardiovascular end point reduction is an important question to be addressed in multicenter, prospective, randomized trials. Our paradigm stresses the fact that patients with renovascular hypertension require intensive blood pressure control and cardiovascular risk factor intervention, both before and after revascularization. Hence, management of such patients requires close attention and periodic review regarding restenosis and progression of vascular 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.     

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.     

Reducing cardiovascular morbidity and mortality from hypertension in end-stage renal disease

Hypertension typically worsens with declining renal function, and is an almost universal feature of end-stage renal disease. Treating hypertension clearly reduces the likelihood of cardiovascular disease in nonrenal populations, with greater absolute benefit in those who have greater severity of underlying cardiovascular disease. Patients with chronic renal diseases are at enormous cardiovascular risk. Although our approach to hypertension in patients with early renal insufficiency has become more aggressive, the rationale has switched over the past decade from cardiovascular risk reduction to slowing the loss of renal function. Reliance on observational studies, especially using mortality as the outcome, has not allowed a consistent, rational approach to the treatment of hypertension in dialysis patients.     

Is embolic protection during renal artery intervention really necessary?

Atherosclerotic renovascular disease is an increasingly recognized cause of both renal function impairment and hypertension, and its presence is associated with increased cardiovascular mortality and dialysis dependence. Although surgical renal revascularization is associated with the most favorable reported renal function outcomes, the significant perioperative mortality and complication rates have resulted in a shift to renal artery percutaneous transluminal angioplasty and stenting (RA-PTAS) as the most frequently performed method of revascularization. Renal function outcomes following RA-PTAS are less favorable, with patients experiencing functional improvement and deterioration with approximately equal frequency in reported series. Distal atheroembolization is thought to occur during RA-PTAS and has been suggested as a potential cause of the disparate renal function outcomes. Distal embolic protection devices primarily used and evaluated in the coronary and cerebrovascular circulations have also been successfully employed during RA-PTAS. Initial clinical results following RA-PTAS with distal embolic protection have been promising, with high rates of technical success, renal function outcomes that approximate those reported with open surgical revascularization, and maintenance of relatively low death and complication rates. Further investigation with controlled comparison groups is warranted before routine use of distal embolic protection can be uniformly endorsed.     

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.     

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.     

Atherosclerotic process, renovascular disease and outcomes from bench to bedside

PURPOSE OF REVIEW: Atherosclerotic renal artery stenosis has become an important cause of secondary hypertension and renal dysfunction in the aging population. Its presence increases cardiovascular morbidity and mortality independent of other atherosclerotic risk factors. Therefore, novel renoprotective strategies are needed to decrease the impact of this disease. RECENT FINDINGS: Although medical therapy can be effective in patients with atherosclerotic renal artery stenosis and mild renal dysfunction, revascularization is desirable for patients with target-organ injury. Technical developments (such as drug-eluting or low-profile stents and distal protection devices) have increased the safety and effectiveness of renal revascularization, but in a significant proportion of patients renal function is not fully restored. Recent experimental evidence suggests that atherosclerotic renal artery stenosis is associated with the activation of intrarenal fibrogenic and inflammatory pathways, oxidative stress, and microvascular remodeling, and blocking these mechanisms can improve renal hemodynamics and function. SUMMARY: Despite significant advances in revascularization techniques, it remains unclear why the kidney affected by atherosclerotic renal artery stenosis often does not improve or even progressively deteriorates. In addition to the restoration of blood flow, targeted interventions to attenuate injurious intrarenal mechanisms should probably become part of a comprehensive management plan to preserve the ischemic kidney.     

Renal artery stenosis of solitary kidney: the dilemma

BACKGROUND: Renal artery stenosis is an important cause of hypertension and renal failure. When present in a solitary kidney, it is associated with extremely high morbidity and mortality. Although guidelines suggest an aggressive approach by revascularization in these cases, available evidence is too weak and contradictory to provide definite recommendations for treatment. OBJECTIVES: To discuss the various clinical factors predicting the benefit from revascularization. METHODS AND RESULTS: Review of more recent clinical trials is presented. DISCUSSION: The approach to the patient with single kidney and renal artery stenosis is discussed and, although there is insufficient evidence-based medicine for guidelines, some suggestions are made to predict revascularization results in these cases. CONCLUSION: Continuous development of clinical prediction rules will help in the management of renal artery stenosis of solitary kidney.     

Concomitant renal revascularization with aortic surgery: are the risks of combined procedures justified?

Indications for concomitant renal revascularization during aortic surgery are not well established. Higher mortality and poorer results are often cited. To examine this, all combined aortic and renal revascularization procedures from August 1992 until May 1998 were reviewed. Of 2003 major arterial reconstructions performed on the Vascular Teaching Service, 45 patients (2%) underwent renal revascularization. Of these 31 patients (69%) had combined aortic and renal procedures. Aortic pathology in these 31 patients (54% male, 94% white, median age 64 years) included arterial occlusive disease (n = 21; 47%), abdominal aortic aneurysm (n = 6; 13%), and thoracoabdominal aortic aneurysm (n = 4; 9%). In all 31 cases the patient presented because of the aortic pathology. Indications for concomitant renal revascularization included renovascular hypertension (n = 21; 68%) and preservation of renal function (n = 10; 32%). Renal revascularization procedures included transaortic endarterectomy (n = 23; 74%), renal bypass (n = 7; 23%), and both bypass and endarterectomy (n = 1; 3%). Seven (22%) complications and two (6%) deaths (both patients operated on for renal salvage) occurred perioperatively. Complications included wound infection (n = 2; 6%), postoperative bleeding (n = 1; 3%), respiratory failure (n = 1; 3%), deep venous thrombosis (n = 1; 3%), cerebrovascular accident (n = 1; 3%), and pseudomembranous enterocolitis (n = 1; 3%). All patients either were cured of their hypertension (n = 5; 24%) or were improved (n = 16; 76%) at 3 months. No patient to date operated on for renal salvage progressed to chronic hemodialysis, but mortality was higher after renal revascularization for renal salvage versus hypertension (20% vs. 0; P = 0.034). There was no significant difference in mortality between the combined aortic/renal procedures versus aortic procedures alone. Despite adding complexity, renal revascularization in patients undergoing aortic surgery appears relatively safe and effective. These data favor an aggressive approach toward renal revascularization in selected patients needing aortic surgery.     

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.     

Cardiorenal Disease: A Clinical Intersection

This review focuses on the association between renal insufficiency and cardiovascular disease and discusses therapeutic options. Although the association of chronic renal insufficiency and cardiovascular risk was first shown in patients with end-stage renal disease, even minor renal dysfunction has now been established as an independent risk for atherosclerotic cardiovascular disease. Treatment with angiotensin-converting enzyme inhibitors and statins can reduce cardiovascular morbidity and mortality in patients with renal insufficiency. Coronary revascularization improves the prognosis in patients with renal dysfunction, but there is still an underutilization of coronary revascularization procedures in patients with renal insufficiency. There is enough data that shows high mortality after percutaneous transluminal coronary angioplasty in patients with reduced renal function and that slight renal dysfunction exposes the patient with a cardiac event to an excessive cardiac mortality. Further investigation should focus on the cause of and possible preventive interventions, for the staggering cardiovascular risk in the ever-increasing number of people with renal dysfunction.     

Percutaneous transluminal revascularization for renal artery stenosis: Veterans Affairs Puget Sound Health Care System experience.

PURPOSE: The safety and efficacy of percutaneous transluminal intervention for renal artery stenosis is improving. This study evaluates the immediate and long-term anatomic and functional outcomes of percutaneous transluminal angioplasty and stenting for atherosclerotic renal artery stenosis in a Veterans Affairs population. METHODS: We performed a retrospective analysis of records from patients who underwent renal artery angioplasty with or without stenting at the Veterans Affairs Puget Sound Health Care System between January 1990 and June 1999. Indications for intervention included hypertension (78%) and rising serum creatinine (78%). Seventy-six patients (74 men, average age of 67 years, range 42-83 years) underwent 88 attempted interventions. Seventy-two percent of contralateral kidneys had significant disease (47% had a >60% stenosis; 16% were nonfunctioning or absent). RESULTS: Of the 88 planned interventions, 86 were successfully performed with placement of 46 stents (52%). Technical success (defined by <30% residual stenosis) was achieved in 78 vessels (89%). The procedure-related complication rate was 5%. Patient mortality by life table analysis was 49% at 5 years. Assisted primary patency rate at 5 years was 100%. Primary and secondary restenosis rates were 37% +/- 8% and 31% +/- 8% at 5 years, respectively. Sixty-eight percent of patients treated for hypertension demonstrated clinical benefit (improved or cured hypertension). This clinical benefit was maintained in 52% of the patients at 5 years, as measured by life table analysis. Serum creatinine was lowered or maintained in 88% of the patients, but this clinical benefit was only maintained in 25% of patients at 5 years. CONCLUSIONS: Transluminal intervention for clinically symptomatic atherosclerotic renal artery stenosis is technically successful and safe. There are excellent assisted-patency and low restenosis rates. There is immediate clinical benefit for most patients, as evidenced by improved control of hypertension and preservation of renal function. However, within 5 years the benefit is not maintained for either hypertension (50%) or renal function (20%). Therefore, although technically successful, functional outcomes after endoluminal intervention are not maintained in the long term.     

The statins--therapeutic diversity in renal disease?

PURPOSE OF REVIEW: Statins significantly reduce cholesterol synthesis and reduce cardiovascular morbidity and mortality. In addition, they appear to have beneficial effects independent of their ability to lower cholesterol. Recent publications suggesting a potential role for statin therapy in chronic renal insufficiency, hypertension and following organ transplantation are reviewed. RECENT FINDINGS: Pharmacokinetic studies have shown statins to be well-tolerated and effective in patients on long-term haemodialysis, providing equivalent control of lipid levels to that seen in matched controls. Preliminary clinical trials suggest that statins may have beneficial disease-modifying effects in chronic inflammatory disease. Furthermore, immunosuppressive and immunomodulatory actions may confer benefit following cardiac transplantation, but this remains to be demonstrated definitively in renal transplant patients. Data to date suggest that, in addition to reduction of cardiovascular risk, statins may help slow the progress of chronic renal insufficiency, particularly in patients with proteinuria. Addition of statin therapy may also contribute to the control of systemic and pulmonary hypertension. SUMMARY: Encouraging data in support of a wider spectrum of use for statins are emerging. In addition to reduction of cardiovascular risk through lipid lowering, they may represent an important adjunctive therapy in patients with chronic kidney diseases and post-transplantation. However, further large, well-designed clinical trials are required before their widespread use can be recommended in this setting.     

Renal revascularization to preserve and restore renal function.

A total of 97 patients underwent 107 renal revascularization procedures for restoration and preservation of renal function. Of the 4 groups of high risk surgical patients that emerged an overall successful outcome was achieved in 83%, with a 6% mortality rate and an 11% morbidity rate. Renal revascularization for restoration and preservation of renal function can be performed safely with good results. The preoperative serum creatinine level was not predictive of the surgical outcome. Alternative bypass procedures are preferred.     

Are simultaneous aortic reconstruction and renal revascularization safe and effective?

Between 1983 and 1989, 40 patients with uncontrollable hypertension underwent renal revascularization. Of these, 21 patients had simultaneous aortic and renal revascularization. Eleven of the 21 patients (52.4%) had renal insufficiency with a mean creatinine clearance of 0.61 +/- 0.23 ml/sec. Eleven patients had an aortic aneurysm; the remaining 10 patients had aortic occlusive disease of varying severity. Aortic reconstruction was done with either a straight (8 patients) or bifurcated (13 patients) Dacron graft. Renal revascularization was accomplished with either bypass (11 patients) or transaortic endarterectomy (10 patients). One patient died postoperatively secondary to myocardial infarction (operative mortality rate of 4.7%). Among the 11 patients with renal insufficiency the mean creatinine clearance of 0.61 +/- 0.23 ml/sec preoperatively improved to 0.94 +/- 0.30 ml/sec postoperatively (p less than 0.01). In the follow-up period extending to 78 months (mean 39.1 months), one late death occurred. There were no instances of worsening hypertension or deterioration in renal function. Contrary to some previous reports, our results indicate that severe aorto-renal atherosclerosis can be managed with simultaneous aortic reconstruction and renal revascularization at an acceptably low operative risk. In addition, a significant and persisting benefit in both hypertension control and renal dysfunction can be expected after surgery.