The natural history of atherosclerotic and fibrous renal artery disease

From 1969 to 1979, 169 patients with two or more renal angiograms for renovascular disease (85 atherosclerotic, 75 fibrous, 9 atherosclerotic and fibrous) were reviewed in an attempt to characterize progression of disease and to determine clinical markers of progression. Progression of renal artery atherosclerosis was observed in 37 patients (44 per cent); progression to complete occlusion was observed in 14 patients (16 per cent). In the 66 patients with medial fibroplasia, progression was observed in 22 patients (33 per cent). Serial serum creatinine measurements in conjunction with measurements of kidney size may be used as markers of progressive atherosclerotic renovascular disease. These clinical markers did not represent progressive disease for individuals with medial fibroplasia.     

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.     

Atherosclerotic renal artery disease diagnosis update

Atherosclerotic renal artery disease represents a cause of which little is known but not a cause to be neglected for hypertension and renal insufficiency. Even though its occurrence remains badly defined, atherosclerotic renal artery disease is constantly on the rise due to the aging population, the never prevailing hypertension and diabetes mellitus. This review aims to give a clinical profile of patients presenting with atherosclerotic renal artery disease and to discuss, in the light of study results, which diagnostic evaluation should be used considering the sequence and the benefit and risk of each in order to initiate a personalized treatment. Patients affected by atherosclerotic renal artery disease are likely to have more complications and more extensive target-organ damage than patients without renal artery stenosis. The evolution of the atherosclerotic renal artery disease is in general slow and progressive. Nevertheless, certain clinical cases manifest themselves with the onset of acute renal failure bought upon by the administration of blockers of the rennin-angiotensin-aldosterone system, or by some other causes responsible for a sudden drop in renal plasma flow (e.g., thrombosis of the renal artery). The relationship between atherosclerotic renal artery disease and atherosclerosis is complex, and mediators implicated in the pathophysiology of renovascular disease may also contribute to the progression of cardiovascular damage. An early assumption of the atherosclerotic renal artery stenosis is warranted to determine the adapted treatment (i.e., medical treatment, revascularisation...) just as the assumption and the correction of the more general cardiovascular risk factors.     

Natural history of renal artery stenosis.

The natural history of various types of renal artery stenosis is reviewed. Atherosclerotic renal artery stenosis is obviously a progressive disease, with a relatively high incidence of occlusions, particularly when the stenosis is narrow. Much less is known about other types of renal artery stenosis. Medial fibroplasia is obviously a disease which progresses during fertile life, but the course is rather unpredictable. Very little is known about the developmental types of renal artery stenosis.     

Natural history of atherosclerotic renal artery stenosis associated with aortic disease

The natural history of atherosclerotic renal artery stenosis has not been well defined, particularly when discovered in conjunction with aortic disease requiring correction. To better define the natural history of such lesions, 194 sequential aortograms in 48 patients were studied to define predictive criteria for stenoses at risk for progression. Sixty-six unsuspected atherosclerotic renal arterial stenoses were identified on the initial aortograms. Disease progressed in 42 arteries (53%), 14 bilateral and 28 unilateral. Seven arteries developed occlusion. All had stenoses averaging 80% (range 61% to 94%) noted on the most recent aortogram preceding occlusion. Risk factors including smoking, diabetes mellitus, elevated serum lipids, coronary artery disease, peripheral arterial disease, or change in blood pressure or creatinine, did not correlate with degree or rate of progression of the renal artery stenosis. A difference in kidney size, although varying inversely with degree of stenosis, was not a statistically significant marker of disease progression. This analysis suggests that identification of renal arterial stenoses that will progress is best determined by sequential aortography. Highly stenotic vessels are more prone to occlude than those less stenotic. Consequently, individuals with preocclusive lesions should benefit from prophylactic renal revascularization during aortic reconstruction.     

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.     

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.     

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.     

Aortorenal reimplantation in treatment of renovascular hypertension

From 1964 to 1977, 33 patients underwent aortorenal reimplantation as surgical treatment for renovascular hypertension. Over-all results were 13 patients cured (39 per cent), 15 patients improved (46 per cent), and there were 5 failures (15 per cent). The results were equally satisfactory in patients with atherosclerotic or fibrous renal artery disease. Postoperative arterial stenosis or occlusion occurred in 5 patients (15 per cent). Aortorenal reimplantation is an effective method of renal revascularization in properly selected patients, and long-term results are comparable with those of aortorenal bypass.     

Atherosclerotic renal artery stenosis: epidemiology,cardiovascular outcomes,and clinical prediction rules

Atherosclerotic renal artery stenosis is the most common primary disease of the renal arteries, and it is associated with two major clinical syndromes, ischemic renal disease and hypertension. The prevalence of this disease in the population is undefined because there is no simple and reliable test that can be applied on a large scale. Renal artery involvement in patients with coronary heart disease and/or heart failure is frequent, and it may influence cardiovascular outcomes and survival in these patients. Suspecting renal arterial stenosis in patients with recurrent episodes of pulmonary edema is justified by observations showing that about one third of elderly patients with heart failure display atherosclerotic renal disease. Whether interventions aimed at restoring arterial patency may reduce the high mortality in patients with heart failure is still unclear because, to date, no prospective study has been carried out in these patients. Increased awareness of the need for cost containment has renewed the interest in clinical cues for suspecting renovascular hypertension. In this regard, the DRASTIC study constitutes an important attempt at validating clinical prediction rules. In this study, a clinical rule was derived that predicted renal artery stenosis as efficiently as renal scintigraphy (sensitivity: clinical rule, 65% versus scintigraphy, 72%; specificity: 87% versus 92%). When tested in a systematic and quantitative manner, clinical findings can perform as accurately as more complex tests in the detection of renal artery stenosis.     

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.     

Progression of atherosclerotic renovascular disease: A prospective population-based study

OBJECTIVE: Previous reports from select hypertensive patients suggest that atherosclerotic renovascular disease (RVD) is rapidly progressive and associated with a decline in kidney size and kidney function. This prospective, population-based study estimates the incidence of new RVD and progression of established RVD among elderly, free-living participants in the Cardiovascular Health Study (CHS). METHOD: The CHS is a multicenter, longitudinal cohort study of cardiovascular risk factors, morbidity, and mortality among men and women aged >65 years old. From 1995 through 1996, 834 participants underwent renal duplex sonography (RDS) to define the presence or absence of significant RVD. Between 2002 and 2005, a second RDS study was performed in 119 participants (mean study interval, 8.0 +/- 0.8 years). Significant RVD was defined as hemodynamically significant stenosis (renal artery peak systolic velocity [RA-PSV] exceeding 1.8 m/s) or renal artery occlusion. Prevalent RVD was significant RVD at the first RDS, and incident disease was defined as new significant RVD at the second RDS. Significant change of RVD was defined as a change in RA-PSV of greater than two times the standard deviation of expected change over time, regardless of hemodynamic significance or progression to renal artery occlusion. RESULTS: The second RDS study cohort included 119 CHS participants with 235 kidneys (35% men; mean age, 82.8 +/- 3.4). On follow-up, no prevalent RVD (n = 13 kidneys; 6.0%) progressed to occlusion. Twenty-nine kidneys without RVD at the first RDS demonstrated significant change in PSV at the second RDS; including nine kidneys with new significant RVD (8 new stenoses; 1 new occlusion). Controlling for within-subject correlation, the overall estimated change in RVD among all 235 kidneys was 14.0% (95% confidence interval [CI], 9.2% to 21.4%), with progression to significant RVD in 4.0% (95% CI, 1.9% to 8.2%). Longitudinal increase in diastolic blood pressure and decrease in renal length were significantly associated with progression to new (ie, incident) significant RVD but not prevalent RVD. CONCLUSIONS: This is the first prospective, population-based estimate of incident RVD and progression of prevalent RVD among free-living elderly Americans. In contrast to previous reports among select hypertensive patients, CHS participants with a low rate of clinical hypertension demonstrated a significant change of RVD in only 14.0% of kidneys on follow-up of 8 years (annualized rate, 1.3% per year). Progression to significant RVD was observed in only 4.0% (annualized rate, 0.5% per year), and no prevalent RVD progressed to occlusion.     

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.     

Prevalence of atherosclerotic renal artery stenosis in patients starting dialysis.

BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) can lead to end-stage renal failure (ESRF). We determined the prevalence of ARAS in patients 45 years of age or older starting renal replacement therapy. METHODS: Forty-nine of 80 consecutive patients (37 males, 12 females) starting renal replacement therapy in our centre gave informed consent and underwent spiral computed tomographic angiography of their renal arteries. A renal artery diameter reduction of 50% or more assessed by two radiologists was considered as a significant stenosis. RESULTS: Twenty of 49 patients (41%) had an ARAS, and in eight cases (16%) this was bilateral or unilateral with a single kidney. Women were more likely to have an ARAS than men; 75 (9/12) vs 30% (11/37, P<0.01). However, relatively more women declined participation. Non-participants and participants did not differ in respect to other relevant clinical data. Nonetheless, findings in these patients would be negative, the prevalence of ARAS would still be 31% in women and 22% in men (NS). In 13 patients with ARAS the registered diagnosis of ESRF either was hypertension, renovascular disease or unknown. Assuming that in these patients atherosclerotic renovascular disease was the cause of renal failure, a total of 13 patients (13/49, 27%) entered the dialysis programme because of this problem. CONCLUSIONS: These results suggest that ARAS is an important cause of ESRF.     

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.     

Atherosclerosis in the young: a virulent disease

To learn more about the prognosis of young patients with atherosclerotic cardiovascular disease we reviewed our experience with patients 40 years of age or younger who required surgical intervention for cardiovascular occlusive disease. We identified 47 patients, 25 of whom required peripheral vascular reconstruction and 22 of whom underwent coronary artery bypass grafting. All but one patient were extremely heavy cigarette smokers. Of the 11 women with peripheral vascular disease, eight required operations for limb salvage and three for renovascular hypertension. Four of the 11 women required a total of 11 subsequent operations because of recurrent or progressive disease. Of the 14 men, 13 required intervention for limb salvage and one for renovascular hypertension. Forty-five additional operations, including 15 amputations, were required in these 14 male patients because of recurrent or progressive disease. Of the 22 patients (21 men and one woman) who underwent coronary artery bypass operations, there was one postoperative death. Five patients (23.8%) required a second bypass operation and one patient (4.8%) required a third procedure bypass because of recurrent symptoms and occluded grafts. One patient has occluded grafts and inoperable disease. Atherosclerotic cardiovascular disease in young patients appears to be a virulent disease process and is associated with a high rate of recurrent or progressive disease. There is a striking association between the premature development of atherosclerotic cardiovascular disease and cigarette smoking.     

Non-invasive assessments of cardiovascular disease in patients with renal failure

Vascular calcification is common in patients with chronic renal failure, and it may contribute to the very high mortality rate from cardiovascular causes in the end-stage renal disease population. Vascular calcification in chronic renal failure can arise from the calcification of the intimal layer of arteries as a result of atherosclerosis or from medial wall calcification due largely to alterations in mineral metabolism. Although several reports indicate that coronary artery calcification, as measured by electron-beam computed tomography, is quite common in patients with end-stage renal disease who are treated with dialysis, the clinical significance of these findings remain uncertain. In the general population, electron-beam computed tomography evidence of coronary calcification serves as a useful index of atherosclerotic burden and has value as a predictor of adverse coronary events. The relationship between coronary artery calcification and atherosclerotic cardiovascular disease has not been adequately studied, however, in patients with end-stage renal disease, and calcification scores in this population may reflect both intimal and medial wall calcification. Assessments using coronary angiography are needed to determine the diagnostic value of electron-beam computed tomography as a predictor of atherosclerotic cardiovascular disease in patients with chronic renal failure. Nevertheless, electron-beam computed tomography makes it possible to detect the presence and monitor the progression of coronary calcification in those undergoing long-term dialysis. The technique may provide important information about the impact of new therapeutic strategies aimed at reducing the risks of vascular calcification in those with chronic renal failure.     

Renal infarction secondary to fibrous dysplasia and aneurysm formation of renal artery

We report a case of a previously healthy forty-year-old man with bilateral renal artery stenosis secondary to bilateral medial fibrous dysplasia. He was additionally found to have a dissecting aneurysm of the left upper renal artery branch with resultant infarction of the upper and middle pole renal segments. We believe renal infarction secondary to medial fibrous dysplasia with occlusion of the renal artery associated with a dissecting aneurysm has not been reported, and we report the first such case. A multimodality treatment approach was utilized.