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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The management of renovascular disease: ASTRAL and beyond.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

BACKGROUND: 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. METHODS: 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, RESULTS: 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). CONCLUSIONS: 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.

Effects of renal volume and single-kidney glomerular filtration rate on renal functional outcome in atherosclerotic renal artery stenosis.

BACKGROUND: Renal functional outcome is unpredictable after revascularization of high-grade atherosclerotic renal artery stenosis (RAS). 'Hibernating' parenchyma describes acute parenchymal injury where renal dysfunction is potentially reversible with treatment of the stenosis. We analysed renal parenchymal volume (PV) and single-kidney glomerular filtration rate (SK-GFR) characteristics to identify kidneys with hibernating parenchyma and hence determine renal functional outcome after revascularization. METHODS: Fifty patients with > or =50% RAS underwent baseline analyses: (i) PV using magnetic resonance imaging; (ii) radioisotopic SK-GFR. Twenty-one patients (27 kidneys) underwent renal revascularization and 29 medical therapy alone. RESULTS: Patients with revascularized kidneys manifesting high PV:SK-GFR showed improvement in global estimated GFR compared to conservatively managed counterparts at 6 months and 1 year (6 months: 6.2 +/- 2.9 versus -3.7 +/- 6.8, P = 0.038; 1 year: 3.5 +/- 3.0 versus -5.1 +/- 5.1 ml/min/1.73 m(2), P = 0.021). Twelve revascularized patients (16 kidneys) underwent repeat SK-GFR 4 months post-revascularization. Six of 16 revascularized kidneys had high baseline PV:SK-GFR and showed improved SK-GFR compared to kidneys with low or normal PV:SK-GFR (6.3 +/- 2.0 versus -0.9 +/- 4.2 ml/min, P = 0.002). CONCLUSIONS: Our data suggest that, after revascularization, GFR improvement is likely if there is a disproportionately higher baseline PV:SK-GFR in the RAS kidney. Analysing these parameters can potentially identify these 'hibernating' kidneys and aid determination of renal functional outcome in RAS.

Management of acute renal failure in the elderly patient: a clinician's guide.

Numerous anatomical and functional changes occurring in the aging kidney lead to reduced glomerular filtration rate, lower renal blood flow and impaired renal autoregulation. The elderly are especially vulnerable to the development of renal dysfunction and in this population acute renal failure (ARF) is a common problem. ARF is often iatrogenic and multifactorial; common iatrogenic combinations include pre-existing renal dysfunction and exposure to nephrotoxins such as radiocontrast agents or aminoglycosides, use of NSAIDs in patients with congestive cardiac failure and use of ACE inhibitors and diuretics in patients with underlying atherosclerotic renal artery stenosis. The aetiology of ARF is classically grouped into three categories: prerenal, intrinsic and postrenal. Prerenal ARF is the second most common cause of ARF in the elderly, accounting for nearly one-third of all hospitalized cases. Common causes can be grouped into true volume depletion (e.g. decreased fluid intake), decreased effective blood volume (e.g. systemic vasodilation) and haemodynamic (e.g. renal artery stenosis, NSAID use). Acute tubular necrosis (ATN) is the most common cause of intrinsic ARF and is responsible for over 50% of ARF in hospitalized patients, and up to 76% of cases in patients in intensive care units. ATN usually occurs after an acute ischaemic or toxic event. The pathogenesis of ATN involves an interplay of processes that include endothelial injury, microvascular flow disruption, tubular hypoxia, dysfunction and apoptosis, tubular obstruction and trans-tubular back-leak. Vasculitis causing ARF should not be missed as this condition is potentially life threatening. The likelihood of a postrenal cause for ARF increases with age. Benign prostatic hypertrophy, prostatic carcinoma and pelvic malignancies are all important causes. Early identification of ARF secondary to obstruction with renal imaging is essential, and complete or partial renal recovery usually ensues following relief of the obstruction.A comprehensive medical and drug history and physical examination are all invaluable. Particular attention should be paid to the fluid status of the patient (skin turgor, jugular venous pressure, lying and standing blood pressure, urine output). Urinalysis should be performed to detect evidence of proteinuria and haematuria, which will aid diagnosis. Fractional excretion of sodium and urine osmolality may be measured but the widespread use of diuretics in the elderly gives rise to unreliable results. Renal imaging, usually ultrasound scanning, is routinely performed for assessment of renal size and to exclude urinary obstruction. In some cases, renal biopsy is necessary to provide specific diagnostic information. The general principles of managing ARF include treatment of life-threatening features such as shock, respiratory failure, hyperkalaemia, pulmonary oedema, metabolic acidosis and sepsis; stopping and avoiding administration of nephrotoxins; optimization of haemodynamic and fluid status; adjustment of drug dosage appropriate to glomerular filtration rate; early nutritional support; and early referral to nephrologists for diagnosis of ARF cause, timely initiation of dialysis and initiation of specific treatment. The treatment of prerenal and ATN ARF is largely supportive with little evidence of benefit from current pharmacological therapies. Despite advances in critical care medicine and renal replacement therapy, the mortality of ARF has not changed significantly over the last 40 years, with current mortality rates being up to 75%.

The effects of statins on the progression of atherosclerotic renovascular disease.

BACKGROUND/AIMS: The aim was to examine the influence of statin therapy on the natural history of atherosclerotic renal artery stenosis (RAS). METHODS: Our hospital atherosclerotic renovascular disease (ARVD) database was analysed for patients who underwent repeat renal angiography during clinical follow-up. Patients with >or=1 RAS lesion and >or=4 months between baseline and repeat renal angiography were analysed. 79 patients were included. Baseline renal arterial anatomy was classified as normal, 50% RAS or renal artery occlusion. RESULTS: Mean follow-up time between angiograms was 27.8 +/- 22.3 (4.0-101.9) months. Progression of RAS occurred in 28 (23%) vessels, regression in 14 (12%) and no significant change in 79 (65%). Multivariate regression analysis showed that baseline proteinuria >0.6 g/day increased the risk of progressive disease (relative risk, RR, 3.8; 95% confidence interval, CI, 1.2-12.1), treatment with statin reduced the risk of progression (RR 0.28; 95% CI 0.10-0.77). 14 renal arteries from 12 patients showed RAS regression with a greater proportion on statin [statin treatment 10 (83%) versus no statin treatment 2 (17%), p = 0.001]. Change in estimated glomerular filtration rate (eGFR) per year was not different between statin- and no-statin-treated groups. CONCLUSIONS: Progression or development of RAS was significantly less likely to occur with statin therapy. Delta eGFR did not correlate with progression of RAS, reflecting the importance of intrarenal injury in the aetiology of renal dysfunction. Our results suggest statin therapy can alter the natural history of ARVD.

Measurement of single kidney function using dynamic contrast-enhanced MRI: comparison of two models in human subjects.

PURPOSE: To compare two methods for assessing the single kidney glomerular filtration rate (SK-GFR) in humans using dynamic contrast-enhanced (DCE)-MRI. MATERIALS AND METHODS: Images were acquired from 39 separate MR studies of patients with atherosclerotic renovascular disease (ARVD). Data from the kidneys and descending aorta were analyzed using both a Rutland-Patlak plot and a compartmental model. MR estimates of the SK-GFR were compared with standard radioisotope measures in a total of 75 kidneys. RESULTS: Estimates of renal function using both techniques correlated well with radioisotope-assessed SK-GFR (Spearman's rho=0.81, Rutland-Patlak; rho=0.71, compartmental model). The Rutland-Patlak approach provided a near one-to-one correspondence, while the compartmental method tended to overestimate SK-GFR. However, the compartmental model fits to the experimental data were significantly better than those obtained using the Rutland-Patlak approach. CONCLUSION: DCE-MRI of the kidneys provides data that correlate well with reference measures of SK-GFR. However, further work, including image registration, is needed to isolate measurement of glomerular filtration to the level of the renal cortex.

The unrecognized prevalence of chronic kidney disease in diabetes.

BACKGROUND: Diabetes mellitus and chronic kidney disease (CKD) are common and exhibit synergistic associations with premature mortality. Current diabetes guidelines in the UK recommend annual urinary albumin and serum creatinine determinations to screen for diabetic kidney disease. The aim of this study was to estimate the burden of CKD in patients with diabetes and examine the ability of serum creatinine and albuminuria to detect clinically meaningful CKD compared with estimated glomerular filtration rate (eGFR). METHODS: All adults known to have diabetes in primary and secondary care in Salford, UK, alive with independent renal function on 1 January 2004 were included in this observational study (n=7596). Demographic and laboratory parameters were obtained from the Electronic Patient Record. eGFR was determined using the 4-variable modification of diet in renal disease (MDRD) formula. Clinically meaningful CKD was defined as an eGFR <60 ml/min/1.73 m(2). RESULTS: Creatinine and albuminuria were measured in the preceding 2 years in 82.3 and 55.2% of subjects, respectively. In patients with CKD, normoalbuminuria was present in 48.8%, and serum creatinine was normal (or=120 micromol/l) had a sensitivity and specificity of 45.3 and 100%, respectively, to identify CKD. The combination of abnormal creatinine and albuminuria had an improved performance but still failed to detect a large number with CKD (sensitivity 82.4%, specificity 75.4%). Serum creatinine failed to identify CKD more often in females (OR 8.22, CI 6.56-10.29). CONCLUSIONS: Undiagnosed CKD is common in diabetes. Current screening strategies, based on creatinine or albuminuria, fail to identify a considerable number of subjects with CKD. Incorporating eGFR into screening for CKD would identify individuals earlier in the natural history of the disease and enable early effective treatment to delay progression of CKD.

Dilemmas in the management of renal artery stenosis.

Atherosclerotic renovascular disease (ARVD) accounts for >90% of renal artery stenosis (RAS) in Western populations; the remainder are due to fibromuscular disease (FMD). The epidemiology is quite different in the Indian subcontinent and the Far East where Takayasu's arteritis may be responsible for up to 60% of RAS cases. ARVD is very commonly associated with hypertension and renal dysfunction; it is a disease of ageing and is frequently observed in association with other vascular diseases. There is increasing evidence that in patients with ARVD and chronic renal dysfunction the aetiology of the latter is more often due to long-standing intra-renal vascular disease and parenchymal injury than to reversible ischaemia. This is reflected in the variability in renal functional outcome following revascularization, with an improvement in renal function being observed in only a minority of patients; the majority show no apparent change or even a decline in renal function. A major current challenge concerns the identification of patients who are likely to benefit from renal revascularization procedures, but technological advances in imaging offer potential in aiding this selection. Large-scale randomized controlled trials are required to determine the overall effects of renal artery intervention and, more specifically, to help identify which subgroups of patients will benefit from revascularization.

Epidemiology of renal dysfunction and patient outcome in atherosclerotic renal artery occlusion.

Patients with atherosclerotic renal artery occlusion (RAO) effectively have only a single functioning kidney, so they constitute an ideal group in whom to study the relationship of atherosclerotic renovascular disease (ARVD) severity to renal functional outcome. Of 299 patients with ARVD who had presented to a single center over a 12-yr period, 142 (47.5%) patients with RAO were identified. There was no relationship between baseline renal function and contralateral renovascular anatomy. Patients with contralateral normal, insignificant (<50%), or significant (>50%) renal artery stenoses had baseline creatinine of 243 +/- 235, 292 +/- 197, or 210 +/- 102 micromol/L, respectively, but patients with bilateral RAO (creatinine, 540 +/- 304 micromol/L; P < 0.0001) were significantly worse. There were significant correlations between baseline GFR and both proteinuria (r = -0.32; P < 0.01) and contralateral bipolar renal length (r = 0.44; P < 0.0001). Over a mean follow-up period of 31 +/- 21 (2 to 82) mo, the overall rate of progressive renal functional decline was -4.1 ml/min per yr. Nine patients required dialysis at presentation and a further 15 (10.5%) during the course of the study. There were 85 (59.9%) deaths; median survival of the whole group was 25 mo, and 5-yr survival was 31%. Multivariate analysis indicated that low baseline GFR was the chief variable independently associated with increased probability of death or need of dialysis but that renal vascular anatomy had no prognostic impact. This study reinforces the importance of intrarenal vascular and parenchymal disease in the etiology of renal dysfunction in ARVD.