Atherosclerotic Renal Vascular Disease Research Articles

Atherosclerotic-nephropathy: an updated narrative review.

The increased prevalence of chronic kidney disease (CKD) in elderly patients recognizes, as main cause, the long-term exposure to atherosclerosis and hypertension. Chronic ischemic damage due to critical renal arterial stenosis induces oxidative stress and intra-renal inflammation, resulting in fibrosis and microvascular remodelling, that is the histological picture of atherosclerotic renal vascular disease (ARVD). The concomitant presence of a long history of hypertension may generate intimal thickening and luminal narrowing of renal arteries and arterioles, glomerulosclerosis, interstitial fibrosis and tubular atrophy, more typically expression of hypertensive nephropathy. These complex mechanisms contribute to the development of CKD and the progression to End Stage Kidney Disease. In elderly CKD patients, the distinction among these nephropathies may be problematic; therefore, ischemic and hypertensive nephropathies can be joined in a unique clinical syndrome defined as atherosclerotic nephropathy. The availability of novel diagnostic procedures, such as intra-vascular ultrasound and BOLD-MRI, in addition to traditional imaging, have opened new scenarios, because these tools allow to identify ischemic lesions responsive to renal revascularization. Indeed, although trials have deflated the role of renal revascularization on the renal outcomes, it should be still used to avoid dialysis initiation and/or to reduce blood pressure in selected elderly patients at high risk. Nonetheless, lifestyle modifications (smoking cessation, increased physical activity), statins and antiplatelet use, as well as cautious use of renin-angiotensin system inhibitors, remain the main therapeutic approach aimed at slowing the renal damage progression. Mesenchymal stem cells and Micro-RNA are promising target of anti-fibrotic therapy, which might provide potential benefit in ARVD patients, though safety and efficacy profile in humans is unknown too.

Cardiac structure and function after revascularization versus medical therapy for renal artery stenosis: the ASTRAL heart echocardiographic sub-study

BackgroundThe ASTRAL trial showed no difference in clinical outcomes between medical therapy and revascularization for atherosclerotic renal vascular disease (ARVD). Here we report a sub-study using echocardiography to assess differences in cardiac structure and function at 12 months.MethodsASTRAL patients from 7 participating centres underwent echocardiography at baseline and 12 months after randomisation. Changes in left ventricular ejection fraction (LVEF), left ventricular mass (LVM), left atrial diameter (LAD), aortic root diameter (AoRD), E:A, and E deceleration time (EDT) were compared between study arms. Analyses were performed using t-tests and multivariate linear regression.ResultsNinety two patients were included (50 medical versus 42 revascularization). There was no difference between arms in any baseline echocardiographic parameter. Comparisons of longitudinal changes in echocardiographic measurements were: δLVEF medical 0.8 ± 8.7% versus revascularization − 2.8 ± 6.8% (p = 0.05), δLVM − 2.9 ± 33 versus − 1.7 ± 39 g (p = 0.9), δLAD 0.1 ± 0.4 versus 0.01 ± 0.5 cm (p = 0.3), δAoRD 0.002 ± 0.3 versus 0.06 ± 0.3 cm (p = 0.4), δE:A − 0.0005 ± 0.6 versus 0.03 ± 0.7 (p = 0.8), δEDT − 1.1 ± 55.5 versus − 9.0 ± 70.2 ms (p = 0.6). In multivariate models, there were no differences between treatment groups for any parameter at 12 months. Likewise, change in blood pressure did not differ between arms (mean δsystolic blood pressure medical 0 mmHg [range − 56 to + 54], revascularization − 3 mmHg [− 61 to + 59], p = 0.60).ConclusionsThis sub-study did not show any significant differences in cardiac structure and function accompanying renal revascularization in ASTRAL. Limitations include the small sample size, the relative insensitivity of echocardiography, and the fact that a large proportion of ASTRAL patient population had only modest renal artery stenosis as described in the main study.

Hypertension in Patients with Chronic Kidney Disease

The prevalence of hypertension in chronic kidney disease (CKD) patients exceeds that of the general population. Uncontrolled hypertension plays a significant role in progression to end stage renal disease and results in increased cardiovascular morbidity and mortality. A complex interplay between various pathophysiologic mechanisms is responsible for the development of hypertension in this patient population. The major factors being extracellular volume overload, increased endothelin-1 release and excess renin-angiotensin-aldosterone system and sympathetic nervous system activity. Dietary and lifestyle modifications have synergistic effects to drug therapy in the control of hypertension. There is no single blood pressure target that is optimal for all CKD patients. It is important to individualize the treatment depending on age, the severity of albuminuria, and comorbidities. Drugs blocking the renin-angiotensin-aldosterone system are the recommended first-line antihypertensive agents for most CKD patients. Intradialytic hypertension may be prevented by individualizing the dialysis prescription and using nondialyzable antihypertensives. New onset of hypertension in the elderly or new onset of difficult to control hypertension in a previously well controlled hypertensive patient should prompt the work up for atherosclerotic renal vascular disease.

Natural history and progression of atherosclerotic renal vascular stenosis

Date written: December 2008Final submission: October 2009

Renal Athersosclerotic reVascularization Evaluation (RAVE Study): Study protocol of a randomized trial [NCT00127738

BackgroundIt is uncertain whether patients with renal vascular disease will have renal or mortality benefit from re-establishing renal blood flow with renal revascularization procedures. The RAVE study will compare renal revascularization to medical management for people with atherosclerotic renal vascular disease (ARVD) and the indication for revascularization. Patients will be assessed for the standard nephrology research outcomes of progression to doubling of creatinine, need for dialysis, and death, as well as other cardiovascular outcomes. We will also establish whether the use of a new inexpensive, simple and available ultrasound test, the renal resistance index (RRI), can identify patients with renal vascular disease who will not benefit from renal revascularization procedures[1].Methods/designThis single center randomized, parallel group, pilot study comparing renal revascularization with medical therapy alone will help establish an infrastructure and test the feasibility of answering this important question in clinical nephrology. The main outcome will be a composite of death, dialysis and doubling of creatinine. Knowledge from this study will be used to better understand the natural history of patients diagnosed with renal vascular disease in anticipation of a Canadian multicenter trial. Data collected from this study will also inform the Canadian Hypertension Education Program (CHEP) Clinical Practice Guidelines for the management of Renal and Renal Vascular Disease. The expectation is that this program for ARVD, will enable community based programs to implement a comprehensive guidelines based diagnostic and treatment program, help create an evidence based approach for the management of patients with this condition, and possibly reduce or halt the progression of kidney disease in these patients.DiscussionResults from this study will determine the feasibility of a multicentered study for the management of renovascular disease.

Atherosclerotic ischemic renal vascular disease: do published outcomes justify the overzealous diagnostic approaches?

Atherosclerotic renal vascular disease is being recognized more frequently in an elderly patient population with chronic kidney disease. It also is much easier to diagnose and treat, at this time, because of the wide availability of coronary angiography and other radiologic imaging studies. In general, patients with atherosclerotic ischemic renal vascular disease are much sicker than the usual ESRD patient with more cardiac comorbidity and higher mortality rates. It is important to determine whether the lesions in the renal artery are physiologically significant before performing an intervention. The interventions are often risky with significant morbidity. Nephrologists should guide their colleagues to follow prudent courses of action. There are no evidence-based guidelines in this area.

Atherosclerotic renal vascular disease (ASRVD) effect of primary stent placement on blood pressure (BP) and renal function

Atherosclerotic renal vascular disease (ASRVD) effect of primary stent placement on blood pressure (BP) and renal function

The Role of Hypertension, Obesity, and Diabetes in Causing Renal Vascular Disease

The Jackson Heart Study will be an epidemiological study of African Americans in Jackson, Mississippi, to identify risk factors for development and progression of cardiovascular disease. One of the potential risk factors to be assessed in this study is renal vascular disease. Atherosclerotic renal vascular disease is a disease of the elderly, is predominantly seen in white people, and is strongly associated with diffuse atherosclerotic disease and high-grade hypertensive retinopathy. Patients with ischemic nephropathy may constitute up to 16% of new dialysis patients and die more quickly while on renal replacement therapy. Although often not present, hypertension is a commonly observed consequence (but probably not a cause) of renal vascular disease, and the control of blood pressure may not halt the progression of the disease. Approximately 2025% of patients with moderate to severe renal artery stenosis will be diabetic. Diabetic patients fair less well with intervention and have a higher progression to end-stage renal disease or death. Obesity is not commonly seen in patients with renal vascular disease. The Jackson Heart Study may be able to assess the true incidence of atherosclerotic renal vascular disease in African Americans and its impact of cardiovascular morbidity and mortality.

The role of hypertension, obesity, and diabetes in causing renal vascular disease.

The Jackson Heart Study will be an epidemiological study of African Americans in Jackson, Mississippi, to identify risk factors for development and progression of cardiovascular disease. One of the potential risk factors to be assessed in this study is renal vascular disease. Atherosclerotic renal vascular disease is a disease of the elderly, is predominantly seen in white people, and is strongly associated with diffuse atherosclerotic disease and high-grade hypertensive retinopathy. Patients with ischemic nephropathy may constitute up to 16% of new dialysis patients and die more quickly while on renal replacement therapy. Although often not present, hypertension is a commonly observed consequence (but probably not a cause) of renal vascular disease, and the control of blood pressure may not halt the progression of the disease. Approximately 20-25% of patients with moderate to severe renal artery stenosis will be diabetic. Diabetic patients fair less well with intervention and have a higher progression to end-stage renal disease or death. Obesity is not commonly seen in patients with renal vascular disease. The Jackson Heart Study may be able to assess the true incidence of atherosclerotic renal vascular disease in African Americans and its impact of cardiovascular morbidity and mortality.

A patient centered approach to the treatment of renal vascular disease to prevent end stage renal failure.

Atherosclerotic renal vascular disease (RVD) is a cause of renal failure especially in the elderly. There has never been a clinical trial to determine how effective invasive therapy is over medical therapy to prevent end stage renal disease. The objective of this study was to determine how effective invasive therapy for RVD to prevent renal failure should be from the perspective of the patient to warrant implementation. Subjects included 28 elderly dialysis patients and 26 renal health care workers (HCW). Subjects were asked directly how effective invasive therapy should be if they were to undertake the procedure. Invasive therapy would have to eliminate the need for dialysis permanently by 41 +/- 6% for the dialysis patients and 21 +/- 4% for the HCW to be acceptable. This difference in efficacy between the two groups was statistically significant (P = 0.014). Efficacy was also determined using a medical decision analysis model that incorporated patient health related quality of life status for dialysis and non-dialysis. To be cost-effective (< $50,000 incremental cost/quality adjusted life year) invasive therapy had to reduce the development of end stage renal failure by 35 +/- 1% (M +/- SE) for dialysis patients and 15 +/- 1% for HCW. These results show that patients demand better efficacy rates than their providers and that this difference appears to be appropriate based on their perceptions of health and projected outcomes. Both patient and health care workers are more conservative than predicted by the medical decision analysis model. Since the range of patient responses was large, methods of documenting patient perspectives for risky procedures may help clinicians determine how aggressively to investigate and treat patients with RVD.

Preliminary description of focal segmental glomerulosclerosis in patients with renovascular disease

Summary Background Primary and secondary forms of focal segmental glomerulosclerosis (FSGS) are common causes of glomerular proteinuria. Secondary forms of FSGS seem to be the result of adaptive changes that follow a reduction in renal mass. We saw an elderly patient with severe bilateral renal vascular disease (RVD) who had FSGS on percutaneous biopsy. To find out whether elderly patients with atherosclerotic RVD are predisposed to the development of FSGS, we reviewed all cases of FSGS at our institution between 1990 and 1995. Methods We identified 59 cases of biopsy-proven FSGS and examined clinical, histological, and radiographic records. Findings Of the 59 patients, 24 were older than 50 years; eight of these had RVD. No patient under the age of 50 had RVD. Seven of the eight patients with RVD and FSGS had substantial proteinuria at presentation. All had typical glomerular lesions with focal segmental tuft collapse and synechiae; other glomeruli were hypertrophic. All patients showed further decline in renal function on follow-up. Interpretation The association of FSGS and RVD may represent an under-recognised aetiology of significant proteinuria in elderly patients.

Renal Artery Pressure Gradients in Patients With Angiographic Evidence of Atherosclerotic Renal Artery Stenosis

From October 1979 to August 1991, 231 patients underwent renal artery balloon angioplasty at The Ohio State University Hospitals. Atherosclerotic renal vascular disease was present in 171 of these patients. From this cohort, 138 patients undergoing their first angioplasty had renal artery pressure gradients performed before and after renal artery angioplasty. The demographics of this group included age 66.9 ± 10 years (±SD), male 51%, white 94%, black 6%, diabetes mellitus 28%, systolic blood pressure 157 ± 26 mm Hg, diastolic blood pressure 86 ± 13 mm Hg, standard daily doses of antihypertensive medications 4.2 ± 3, and serum creatinine 2.6 ± 2.3 mg/ dL. Plasma renin activity was measured in 25 patients and was shown to be elevated in 16. The renal artery stenoses were main renal artery 75%, orificial 22%, distal renal artery 1.4%, and combinations of the above 2.2%. Solitary kidneys were present in six patients (4.3%). Bilateral renal artery stenosis was present in 45% of patients and bilateral angioplasties were performed in one third of these patients. The preangioplasty systolic blood pressure gradient was 109 ± 50 mm Hg (range, 20 to 230 mm Hg) and the postangioplasty renal artery pressure gradient was 12 ± 16 mm Hg (range, 0 to 78 mm Hg) (P < 0.001). There were no complications related to measurement of the pressure gradients. The magnitude of the renal artery pressure gradients did not correlate with blood pressure level, number of antihypertensive medications, or serum creatinine level. In conclusion, measurement of renal artery pressure gradients is safe and useful in defining hemodynamic significance and immediate response to angioplasty of stenotic renal artery lesions. Whether the reduction in renal artery pressure gradients achieved by the angioplasty is a predictor of the long-term success of the procedure is the subject of an ongoing study.

Treatment of Renovascular Hypertension with Percutaneous Transluminal Angioplasty: Experience in Spain

The clinical results of percutaneous transluminal angioplasty (PTA) were evaluated in patients with renovascular hypertension, and the effect of PTA on blood pressure and renal function was determined. Between February 1982 and December 1990, 93 hypertensive patients underwent 123 renal artery PTA procedures. Mean patient age was 43.4 years (range, 12-78 years). Average baseline blood pressure was 162/111 mm Hg (range, 140-230/95-150 mm Hg). The cause of renovascular hypertension, as determined with angiography, was atherosclerosis in 37 patients, fibromuscular dysplasia in 27, and mixed disease in one; 28 patients had renal transplant arterial stenosis. In patients with atherosclerotic renal vascular disease or fibromuscular renal artery stenosis, systolic and diastolic blood pressure decreased significantly (P < .001) at 96 months after PTA. In patients with renal transplant arterial stenosis, blood pressure also decreased significantly (P < .001) at 12 months after PTA. Technical success was achieved in 78% of patients with atherosclerosis, 92% of patients with fibromuscular dysplasia, and 76% of patients with renal transplants. Complications were seen in 4.8% and were related to renal failure and vessel dissection. PTA is the therapy of choice in patients with renovascular hypertension due to fibromuscular dysplasia. Patients with atherosclerotic renal artery stenosis or stenosis of a renal artery in a transplanted kidney should be selected according to the anatomy of the lesion and clinical patient characteristics.

Death by withdrawal from dialysis

The reasons for withdrawal from dialysis are not well understood. The goals of this study were to determine the risk of dying by withdrawal from dialysis over time and to elucidate pertinent clinical correlates in 716 long-term dialysis patients. These patients were monitored from the initiation of dialysis through the time of death, transplant or transfer to another program during a 20-yr period from 1970 through 1989. The causes of death in the 340 deceased patients were analyzed. Clinical correlates and associated risk factors were evaluated in the patients who died from withdrawal from dialysis. Withdrawal from dialysis was defined as: "Death with manifestations of uremia because of withdrawal from dialysis. Underlying medical conditions should not have been active, leading to rapid deterioration with imminent death." Withdrawal from dialysis and cardiac events were the second leading cause of death, each accounting for 18.5% of the deaths. Patients stopping dialysis were older at the start of dialysis than were patients dying of other causes (P < 0.0006; Kruskal-Wallis test), with 65.1% of these patients 61 yr of age and older. Cancer, malnutrition, catabolism, and "dissatisfaction with life" were important associations with the decision to withdraw. More than 50% of patients withdrawing from dialysis had either diabetic nephropathy or atherosclerotic renal vascular disease. Withdrawal from dialysis was a common cause of death in these dialysis patients especially if they were over 61 and had systemic diseases such as diabetes mellitus and renal vascular disease. The reasons for a higher incidence of withdrawal in certain programs deserve further study.

Critical perfusion pressure for renal function in patients with bilateral atherosclerotic renal vascular disease: Textor SC, Novick AC, Tarazi RC, et al. Ann Intern Med 1985; 102: 308-14

Critical perfusion pressure for renal function in patients with bilateral atherosclerotic renal vascular disease: Textor SC, Novick AC, Tarazi RC, et al. Ann Intern Med 1985; 102: 308-14

Renovascular disease in the elderly: An analysis of 50 patients

Fifty patients, 65 years of age or older, with renovascular disease were evaluated and treated between 1979 and 1981. Twenty-one patients were treated medically, 21 surgically and 8 with percutaneous transluminal angioplasty of the renal arteries. The age, sex, target organ involvement, initial blood pressure and serum creatinine were similar among the three groups. Sixty-six percent of the medical group demonstrated lower blood pressure. Ninety percent of the surgical group demonstrated a cure or improved blood pressure, and 43% of the patients with percutaneous transluminal angioplasty had improved blood pressure. Renal function deteriorated in 50% of the medical group, 19% of the surgical group and 25% of patients in the percutaneous transluminal angioplasty group. There was one operative death in the surgical group and one death related to percutaneous transluminal angioplasty. The data demonstrate that old age itself is not a contraindication to surgery. If hypertension is resistant to medical therapy, if the patient experiences undesirable side effects from the medications or if renal function is jeopardized, surgical therapy should be considered. More experience with percutaneous transluminal angioplasty is necessary to determine its precise role in managing atherosclerotic renal vascular disease in the elderly.

Critical perfusion pressure for renal function in patients with bilateral atherosclerotic renal vascular disease.

We studied renal plasma flow and glomerular filtration rate during graded blood pressure reduction induced with sodium nitroprusside infusion in 16 hypertensive patients with atherosclerotic renovascular disease. Eight patients with unilateral disease tolerated pressure reduction from 205 +/- 9 (SE)/103 +/- 2 mm Hg to 146 +/- 6/84 +/- 3 mm Hg (p less than 0.01) with no change in total renal function. In 8 other patients with bilateral renal arterial stenosis (all arteries 70% or more stenosed), similar pressure reduction produced marked but reversible decrements in plasma flow (152 +/- 28 mL/min to 66 +/- 13 mL/min; p less than 0.01) and glomerular filtration rate (38 +/- 8 mL/min to 16 +/- mL/min; p less than 0.01). In 4 patients restudied after revascularization, sensitivity of renal function to pressure changes was no longer present. These data indicate that vascular stenosis to the entire renal mass may limit function and provide a means for evaluating patients at risk for loss of renal function during antihypertensive therapy.

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.