Atheromatous Renovascular Disease Research Articles

Attenuation of Renal Functional Decline Following Angioplasty and Stenting in Atherosclerotic Renovascular Disease

Background: To date, renal revascularization has not been shown to be advantageous when compared to optimized medical treatment in patients with atheromatous renovascular disease (ARVD). This study aims to investigate the effect of revascularization in patients with pre-intervention worsening renal function and in those with stable renal function. Patients and Methods: In this single-centre observational study, patients who were diagnosed with at least 60% angiographic stenosis unilaterally or bilaterally between January 1996 and October 2008 and who were followed-up until February 2011 were retrospectively analysed. Evolution of renal function was determined from the slope of reciprocal of serum creatinine (RCr-slope) before and after diagnostic angiography or revascularization; this required 5 or more creatinine measurements before and at least another 5 measurements post-procedure. Patients were divided into 2 groups: one comprising patients with negative RCr-slope before the procedure and a second group of patients with prior positive RCr-slope. A stepwise, adjusted logistic regression was used to determine the OR of revascularization on attenuation of RCr-slope. Results: Data for 52 patients were analysed. Median age was 64 (58-72) and median follow-up was 15 (8-34) months. Only patients with a negative RCr-slope (-0.0078 (95% CI -0.0174, -0.0033) dl/mg/month) who underwent revascularization manifested an improved RCr-slope during follow-up (+0.0013 (95% CI -0.0002, 0.0039) dl/mg/month, p < 0.001). This finding remained statistically significant even after the adjustment for proteinuria and bilateral arterial disease. Conclusion: Revascularization may be indicated for patients with ARVD and progressively worsening renal function. This patient subgroup should ideally be evaluated in future randomized controlled trials.

Characteristics of atheromatous renovascular disease in Dubai: A single-center experience

To determine the characteristics of atherosclerotic renal artery stenosis (ARAS) in a cohort of patients who attended the Nephrology Department of NMC Specialty Hospital in Dubai from 2006 through 2010, including their clinical and investigational features and their response to various remedial modalities, we studied 20 patients with a diagnosis of ARAS based on magnetic resonance angiography. Three (15%) patients developed acute renal failure (ARF) after the initiation of angiotensin converting enzyme inhibitors or angiotensin II receptor blockers and 13 (65%) patients presented with chronic kidney disease (CKD) of either ischemic nephropathy or nephroangiosclerosis etiology. Four (20%) patients presented with resistant arterial hypertension (RAH). Plasma renin activity was elevated in all the patients. Fifteen (75%) patients were diabetics. We conclude that CKD was the main presentation of ARAS followed by RAH and ARF in our study. Diabetes Mellitus was the main risk factor for ARAS found in our study.

Reverse cardiac remodelling and renal functional improvement following bilateral renal artery stenting for flash pulmonary oedema

Acute flash pulmonary oedema (AFPO) is a life-threatening syndrome almost unique to patients with atheromatous renovascular disease (ARVD). Although recurrent AFPO is a widely accepted indication to consider renal revascularization, this is based on a number of case reports/series describing a successful outcome post-procedure. There is limited literature on the pathophysiological mechanisms and treatment effects of revascularization to support this clinical decision making. We report the case of a 65-year-old lady who presented with three episodes of AFPO. Investigations revealed severe bilateral renal artery stenosis. Post-revascularization, she experienced substantial improvement in energy levels and New York Heart Association class, with improvement in her blood pressure and renal function. Post-procedure, there were dramatic improvements in her cardiac morphology and function that were sustained at 1 year (ejection fraction improved from 39 to 65%, left ventricular mass decreased from 161 to 116 g) as well as renal function (isotopic glomerular filtration rate increased from 22.4 to 34.2 mL/min). This report provides new insights into the pathophysiological relationships between renal and cardiac changes in AFPO; the extent of the cardiac morphological changes was striking and unexpected.

Dispelling the myth: the use of renin-angiotensin blockade in atheromatous renovascular disease

Many physicians retain reservations regarding the routine prescription of renin-angiotensin blockade (RAB) in patients with atheromatous renovascular disease (ARVD). Conversely, these patients are in most need of the cardio- and renal protection offered by RAB. This reservation is mostly because of fear of precipitating acute renal deterioration. We aimed to study whether RAB can be used safely in ARVD patients and whether it altered their outcome. Prospective observational study of all ARVD patients presenting to our tertiary referral centre from 1999-2009. Data capture included usage and tolerability of RAB, and correlation with endpoints of cardiovascular events, dialysis or death. Six hundred and twenty-one subjects were available for analysis. Mean age (SD) of the cohort was 71.3 (8.8) years, median (interquartile range) follow-up 3.1 (2.1, 4.8), range 0.2-10.61 years. Seventy-four patients had an intolerance to RAB at study entry. When utilized prospectively, RAB was tolerated in 357 of 378 patients (92%), and this was even seen in 54/69 (78.3%) patients with bilateral>60% renal artery stenosis (RAS) or occlusion. Patients (4/21) who were intolerant of RAB during follow-up (and 12 retrospectively intolerant), underwent renal revascularization which facilitated safe use of these medications post-procedure. On multivariate time-adjusted analysis, patients receiving RAB were significantly less likely to die (P=0.02). RAB is well tolerated even in patients with bilateral severe RAS and reduced mortality in a large group of ARVD patients. We recommend all ARVD patients be considered for RAB therapy unless an absolute contra-indication exists. Intolerance of these agents due to renal dysfunction should be considered an emerging indication for renal revascularization to facilitate their re-introduction.

BOLD imaging: a potential predictive biomarker of renal functional outcome following revascularization in atheromatous renovascular disease

Stenting of the stenosed renal artery is commonly employed in atheromatous renovascular disease (ARVD) in order to revascularize the affected kidney. However, it is still far from clear which patient subgroups should be revascularized as stenting carries small but significant risks. We have previously demonstrated that the ratio of magnetic resonance-measured renal volume to isotopic single kidney glomerular filtration rate (isoSK-GFR) is higher in kidneys which show functional improvement after revascularization. Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) does not require contrast administration and is sensitive to changes in tissue concentration of deoxyhaemoglobin. In this study, we test the hypothesis that baseline BOLD R2* map signal and R2*:isoSK-GFR ratio will provide an additional independent predictive biomarker of response to revascularization. Studies were performed in 28 subjects (16 ARVD and 12 controls). All subjects had R2* mapping and isoSK-GFR measured at baseline and at 4-month follow-up. MRI data were collected on a 3 T whole-body MRI scanner using a coronal dual-echo, 2D gradient-echo breath-hold acquisition. Parenchymal regions of interest (ROIs) were drawn on a representative slice through the middle of the kidney. Parametric maps of R2* were generated and mean values of R2* were calculated for every ROI. The ratio of R2*:isoSK-GFR at baseline was significantly greater in kidneys where renal function improved (5.91 ± 6.51) versus stable (1.78 ± 1.11), deteriorated (2.15 ± 1.79) or controls (1.5 ± 0.91), P = 0.003. R2*:isoSK-GFR ratio that was greater than 95% confidence interval of the control kidneys was 66.7% sensitive, but 85.7% specific in predicting a positive renal functional outcome. These pilot data show that BOLD R2* imaging, presumably by detecting intra-renal deoxyhaemoglobin in still viable 'hibernating' parenchyma, coupled with isoSK-GFR may provide an effective predictive biomarker for positive renal functional response to revascularization. R2* imaging is non-invasive, quick to perform and could provide further insight into reversible parenchymal changes in ARVD kidneys.

Medical therapy for renal artery stenosis

The management of renal artery stenosis remains controversial with randomized trials suggesting that revascularization is no better than medical therapy. Thus all patients with atheromatous renovascular disease should be treated with medical therapy. However optimal therapy has not been clearly defined by atheromatous renovascular disease trials; despite this, there are data to support the use of several pharmacologic agents among this group of patients. Such a regimen should include an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, a β-blocker, a statin and aspirin. Additional therapies will often be required and need to be individualized to a given patient based upon comorbid conditions.

Contemporary management of atherosclerotic renovascular disease: Before and after ASTRAL

Atheromatous renovascular disease is an increasingly common diagnosis in our ageing population. Although there is a wide spread of experience in its treatment, the evidence base is heterogeneous and inconclusive. The Angioplasty and Stenting for Renal Artery Lesions trial has provided some, but not all, answers regarding the place of renal revascularization therapy and has also raised more questions and generated further debate. We present a brief review of the significance of atheromatous renovascular disease, discussion of historical treatments, a short analysis of Angioplasty and Stenting for Renal Artery Lesions, and an exploration of where future research lies.

The management of renovascular disease: ASTRAL and beyond

This review concentrates on the new findings published in the atheromatous renovascular disease (ARVD) literature since the beginning of 2009, a period in which the results of two randomized control trials have been released. The key advances have arisen with respect to the epidemiology of ARVD, the effects of revascularization as demonstrated by the results of randomized controlled trials, an understanding of the pathophysiology of the ischaemic kidney, and also there have been further insights regarding the selection of patients for revascularization utilizing structural and functional imaging. Optimal medical management (and not revascularization therapy) is the established cornerstone for all patients with ARVD. Future studies should be directed to identifying individuals who will significantly benefit from renal revascularization.

The benefit of renal artery stenting in patients with atheromatous renovascular disease and advanced chronic kidney disease

Around 16% of all patients who present with atheromatous renovascular disease (ARVD) in the United States undergo revascularization. Historically, patients with advanced chronic kidney disease (CKD) have been considered least likely to show improvement in renal functional terms, or survival. We aimed to investigate whether differences in outcomes after revascularization compared to medical management might be observed in ARVD patients if stratified by their CKD classes. Two prospective cohorts, a UK center with a traditionally conservative approach, and a German center who undertook a proactive revascularization approach, were compared. An improvement in renal function was defined as > 20% renal improvement at one year's follow-up. To improve validity and comparability, revascularized patients in the UK center were also used within analyses, 347 (UK conservative group), 89 (UK revascularized group), and 472 (German center) patients were included in the analysis. When subdivided by CKD stage, patient ages between the two centers were comparable. Improvements in renal function were observed in twice as many patients who underwent revascularization as compared to medical treatment, particularly in the latter CKD stages, 15.2 (German revascularization) vs. 0% in CKD 1-2, 12.2 (UK), and 32.8 (German) revascularization vs. 14.1% in CKD3, and 53.1 and 53.8 vs. 28.3 in patients with CKD 4-5. The improvements in eGFR were 10.2 (16) and 8.1 (12.5) ml/min/year in the German and UK revascularized groups, respectively, vs. -0.05 (6.8) ml/min/year in the medical cohort in CKD 4-5. Improvements in blood pressure control were noted at 1 year overall and within each CKD category. Multivariate analysis revealed that revascularization independently reduced the risk of death by 45% in all patients combined (RR 0.55, P = 0.013). Although this study has significant methodological limitations, it does shows that percutaneous renal revascularization can improve renal function in advanced CKD (stages 4-5), and that this can provide a survival advantage in prospective analysis.

Epidemiology and Natural History of Atherosclerotic Renovascular Disease

Atheromatous renovascular disease (ARVD) is increasingly suspected and diagnosed, and it commonly presents to several different clinical specialties. In this review, the epidemiology, risk factors, comorbid disease associations, natural history, and prognosis of ARVD is described. Atheromatous renovascular disease is strongly associated with macrovascular pathology in other important vascular beds, especially the coronary, aortoiliac and iliofemoral circulations, and also with structural and functional heart disease. These clinicopathologic relationships contribute to the high morbidity and mortality associated with the condition. Understanding of the natural history of renal artery stenosis may enable intensified treatment strategies to reduce associated risk and improve patient prognosis.

Clinical management of atheromatous renovascular disease

Renal artery stenosis (RAS) is common, being due to atheroma in over 90% of cases in developed countries with the remainder mainly due to fibromuscular disease (FMD). The latter tends to occur in younger patients, predominantly women, and usually presents with severe hypertension; a good outcome can

Role of Renal Function and Cardiac Biomarkers (NT-proBNP and Troponin) in Determining Mortality and Cardiac Outcome in Atheromatous Renovascular Disease

Background and Aims: Patients with atheromatous renovascular disease (ARVD) have high cardiovascular morbidity and mortality. The cardiac markers N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin (cTnT) are easily measured, yet not widely used in renal patients as they are thought to be inaccurate in renal disease. We aimed to see if these markers could be used as prognostic indicators of cardiovascular events (CVEs) and death in ARVD. Methods: Subjects with ARVD treated in 1 renal center in 2003 were prospectively followed up. NT-proBNP and cTnT at baseline were correlated with CVEs and death, echocardiographic findings and degree of renal artery stenosis. Cutoff levels of 0.03 ng/ml (cTnT) and 43 pmol/l (NT-proBNP) were used. Results: Eighty-two patients (mean ± SD age 69 ± 8 years, mean follow-up 40.2 ± 16.6 months) were suitable for analysis. Twenty-nine percent of patients suffered new CVEs, and 37.8% died. Renal function was a significant predictor of CVEs and death. Patients with a raised NT-proBNP were more likely to die than those in the same chronic kidney disease (CKD) category with normal levels (p < 0.0001) even after adjusting for multivariate factors (hazard ratio 8.3 for high proBNP vs. 3.6 for low proBNP in CKD stage 4–5). Conclusion: No study to our knowledge has looked at both NT-proBNP and cTnT as outcome markers in ARVD. Our study shows that renal function is more important as a marker of suffering a CVE. However, raised NT-proBNP is associated with a greater likelihood of death when subdivided by CKD stage. Early risk stratification by simple measurement of these biomarkers may aid in intensifying management in high-risk patients, although further studies to assess the value of this approach are warranted.

ATHEROMATOUS RENOVASCULAR DISEASE: OVERVIEW AND CHALLENGES

Atheromatous renovascular disease (ARVD) is a common and challenging disease. It is increasingly associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD), hypertension and cardiovascular burden. Controversy exists regarding the safest investigative methods as well as optimum treatment of this condition. In this review, we provide an overview of ARVD and discuss the challenges still remaining.

Hypertension and atherosclerotic renal artery stenosis: diagnostic approach.

Atherosclerotic renovascular disease needs noninvasive diagnostic tools to apply to patients having clinical characteristics that can suggest its presence. Color Doppler ultrasonography is a noninvasive, inexpensive diagnostic procedure that is capable, in an experienced hand, of accurately screening for renovascular disease. Magnetic resonance angiography and spiral computed tomography angiography play an ancillary role in detecting atheromatous renovascular disease. Captopril-enhanced renography and scintigraphy and the resistive index at Doppler sonography may be very useful in patients with renal artery stenosis for predicting the response to revascularization.

Increasing the diagnostic yield of renal angiography for the diagnosis of atheromatous renovascular disease.

Atheromatous renovascular disease (ARVD) is a common cause of hypertension and chronic renal failure (CRF). In this unit, intravenous digital subtraction angiography (DSA) (or intraarterial DSA if indicated) is used as a screening angiographic study when ARVD is suspected. However, increased use of these investigations has resulted in a longer waiting time for angiography. As the majority of studies are negative for ARVD, clinical features and results of investigations of patients undergoing angiography were reviewed to identify those having the greatest likelihood of ARVD. The clinical notes were reviewed for all 249 patients undergoing angiography over an 18-month period. Primary indications for investigation were: hypertension 71 (28.5%), CRF 156 (62.7%) and CRF with severe hypertension 22 (8.8%). 12 of the CRF patients had end-stage renal failure. 166 (66.7%) patients had no evidence of ARVD, while only 83 (33.3%) patients showed some degree of ARVD, 29 (35%) of which had bilateral renal artery disease. There was no significant difference between the ARVD group and the non-ARVD group for mean age (69.0 years vs 63.3 years), male to female ratio, history of smoking (68.7% vs 55.4%), severe hypertension (10.8% vs 9.0%), hypercholesterolaemia (61.4% vs 47.0%), diabetes mellitus (28.6% vs 25.3%) or angiotensin converting enzyme inhibitor-related renal dysfunction (9.6% vs 6.1%). More patients in the ARVD group were investigated for CRF than in the non-ARVD group, as reflected by the higher serum creatinine level and the lower creatinine clearance in the ARVD group. 55 (33.1%) of the non-ARVD patients had no comorbid vascular disease, vascular bruits or ultrasound discrepancy in the size of the two kidneys, whereas all ARVD patients had at least one of these features (negative predictive value 100%). All three features were present in 19.3% of ARVD patients but in only 3.0% of the non-ARVD patients (positive predictive value 76.2%, specificity 97%). We plan to rationalize the criteria for angiography in the light of these findings, anticipating an increase in the diagnostic yield of renal angiography from its current 33.3% to above 42%.

Progression of renal failure and hypertensive nephrosclerosis

Data provided by end-stage renal disease (ESRD) registries document a progressive and striking increase in the incidence of hypertension-related ESRD over the years, and its prevalence supports the classic statement that the kidney may be a victim of hypertension. Two clinical conditions should be considered separately when the role of hypertension in progressive renal disease is discussed: (a) hypertension and primary renal disease and (b) progressive renal disease in essential hypertension. The appearance of systemic hypertension is one of the major risk factors for the progressive deterioration of primary renal disease both in experimental models and in humans. Strict blood pressure control is able to significantly reduce the disease progression to renal failure. Angiotensin-converting enzyme inhibitors probably show a better nephroprotective action than other antihypertensive agents. Long-lasting hypertension may induce ESRD in some patients through hypertensive nephrosclerosis. In many cases of progressive renal disease associated with essential hypertension, particularly in elderly Caucasians, atheromatous renovascular disease via renal artery stenosis and/or cholesterol microembolization represent the main cause of ESRD.

B031 Comparison of the acute renal effect of losartan and captopril in atheromatous renovascular disease

B031 Comparison of the acute renal effect of losartan and captopril in atheromatous renovascular disease

New thoughts and unsolved problems in atheromatous renovascular disease.

New thoughts and unsolved problems in atheromatous renovascular disease.

Albuminuria predicts renal functional outcome after intervention in atheromatous renovascular disease.

Atheromatous renovascular disease is increasingly recognized as a cause of renal failure; however, the benefit of intervention on renal function outcome cannot be clearly anticipated. To identify reliable predictor(s) of renal functional outcome after revascularization in patients with atheromatous renovascular disease. The effect of percutaneous transluminal renal angioplasty (n = 5) or surgery (n = 18) on glomerular filtration rate ([99mTc]-diethylene triaminopenta-acetic acid clearance) and renal haemodynamics was prospectively assessed in 23 patients with atheromatous renovascular disease (unilateral occlusion in five, unilateral stenosis in four, stenosis of a single kidney in five, unilateral occlusion associated with contralateral stenosis in six, bilateral stenosis in three). Renal function was altered in 18 patients. At early follow-up study (5 +/- 1 months) after intervention, glomerular filtration rate improved (i.e. increased by more than 15%) in six patients, deteriorated in five and remained unchanged in 12 patients. The change in glomerular filtration rate associated with intervention was inversely correlated with the pre-intervention level of urinary albumin excretion and positively with the change in effective renal plasma flow after intervention. Stepwise regression analysis showed that pre-intervention urinary albumin excretion was the only predictor of the glomerular filtration rate response to intervention. At late follow-up study (32 +/- 6 months, n = 13), glomerular filtration rate was stable compared with early follow-up determination in non-proteinuric patients whereas it had deteriorated further in proteinuric patients. In patients with atheromatous renovascular disease, albuminuria may be considered as a marker of pre-existing intra-renal vascular and glomerular damage and a reliable predictor of renal functional outcome after intervention.

Influence of age on the outcome of percutaneous angioplasty in atheromatous renovascular disease

We compared the efficacy and safety of percutaneous transluminal renal angioplasty for the treatment of renovascular disease in 66 patients. Thirty-four were aged less than 60 years, and 32 more than 60 years. The younger patients had a shorter known duration of hypertension and higher levels of diastolic pressure (6.4 +/- 9 years and 109 +/- 15 mmHg) than the older patients (12.8 +/- 8 years and 101 +/- 11 mmHg, P less than 0.01 for both comparisons). They also had higher creatinine clearance rates (78 versus 46 ml/min, P less than 0.01) and less severe renal artery disease. A total of 70 percutaneous transluminal renal angioplasties were performed in 70 arteries with a technical success rate of 100% in the younger group versus 67% in the older group (P less than 0.01); complications occurred more frequently in the older group. Our data indicate that, when technically successful, percutaneous transluminal renal angioplasty improves blood pressure to a similar extent in both younger and older patients. However, in patients over 60 years, the safety of the procedure is limited by more severe age-associated atheroma of renal and extrarenal arteries.