Constantina Chrysochou

Serum phosphate and mortality in patients with chronic kidney disease

BACKGROUND AND OBJECTIVES Higher phosphate is associated with mortality in dialysis patients but few prospective studies assess this in nondialysis patients managed in an outpatient nephrology clinic. This prospective longitudinal study examined whether phosphate level was associated with death in a referred population. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS Patients (1203) of nondialysis chronic kidney disease (CKD) in the Chronic Renal Insufficiency Standards Implementation Study were assessed. Survival analyses were performed for quartiles of baseline phosphate relative to GFR, 12-month time-averaged phosphate, and baseline phosphate according to published phosphate targets. RESULTS Mean (SD) eGFR was 32 (15) ml/min per 1.73 m(2), age 64 (14) years, and phosphate 1.2 (0.30) mmol/L. Cox multivariate adjusted regression in CKD stages 3 to 4 patients showed an increased risk of all-cause and cardiovascular mortality in the highest quartile compared with that in the lowest quartile of phosphate. No association was found in CKD stage 5 patients. Patients who had values above recommended targets for phosphate control had increased risk of all-cause and cardiovascular death compared with patients below target. The highest quartile compared with the lowest quartile of 12-month time-averaged phosphate was associated with an increased risk of mortality. CONCLUSIONS In CKD stages 3 to 4 patients, higher phosphate was associated with a stepwise increase in mortality. As phosphate levels below published targets (as opposed to within them) are associated with better survival, guidelines for phosphate in nondialysis CKD patients should be re-examined. Intervention trials are required to determine whether lowering phosphate will improve survival.

High-risk clinical presentations in atherosclerotic renovascular disease: prognosis and response to renal artery revascularization

BACKGROUND Current trial data may not be directly applicable to patients with the highest risk presentations of atherosclerotic renovascular disease, including flash pulmonary edema, rapidly declining kidney function, and refractory hypertension. We consider the prognostic implications of these presentations and response to percutaneous revascularization. STUDY DESIGN Single-center prospective cohort study; retrospectively analyzed. SETTING & PARTICIPANTS 467 patients with renal artery stenosis ≥50%, managed according to clinical presentation and physician/patient preference. PREDICTORS Presentation with flash pulmonary edema (n = 37 [7.8%]), refractory hypertension (n = 116 [24.3%]), or rapidly declining kidney function (n = 46 [9.7%]) compared to low-risk presentation with none of these phenotypes (n = 230 [49%]). Percutaneous revascularization (performed in 32% of flash pulmonary edema, 28% of rapidly declining kidney function, and 28% of refractory hypertension patients) compared to medical management. OUTCOMES Death, cardiovascular (CV) event, end-stage kidney disease. RESULTS During a median follow-up of 3.8 (IQR, 1.8-5.8) years, 55% died, 33% had a CV event, and 18% reached end-stage kidney disease. In medically treated patients, flash pulmonary edema was associated with increased risk of death (HR, 2.2; 95% CI, 1.4-3.5; P < 0.001) and CV event (HR, 3.1; 95% CI, 1.7-5.5; P < 0.001), but not end-stage kidney disease, compared to the low-risk phenotype. No increased risk for any end point was observed in patients presenting with rapidly declining kidney function or refractory hypertension. Compared to medical treatment, revascularization was associated with reduced risk for death (HR, 0.4; 95% CI, 0.2-0.9; P = 0.01), but not CV event or end-stage kidney disease, in patients presenting with flash pulmonary edema. Revascularization was not associated significantly with reduced risk for any end point in rapidly declining kidney function or refractory hypertension. When these presentations were present in combination (n = 31), revascularization was associated with reduced risk for death (HR, 0.15; 95% CI, 0.02-0.9; P = 0.04) and CV event (HR, 0.23; 95% CI, 0.1-0.6; P = 0.02). LIMITATIONS Observational study; retrospective analysis; potential treatment bias. CONCLUSIONS This analysis supports guidelines citing flash pulmonary edema as an indication for renal artery revascularization in atherosclerotic renovascular disease. Patients presenting with a combination of rapidly declining kidney function and refractory hypertension also may benefit from revascularization and may represent a subgroup worthy of further investigation in more robust trials.

High-risk clinical presentations in atherosclerotic renovascular disease

BACKGROUND Current trial data may not be directly applicable to patients with the highest risk presentations of atherosclerotic renovascular disease, including flash pulmonary edema, rapidly declining kidney function, and refractory hypertension. We consider the prognostic implications of these presentations and response to percutaneous revascularization. STUDY DESIGN Single-center prospective cohort study; retrospectively analyzed. SETTING & PARTICIPANTS 467 patients with renal artery stenosis ≥50%, managed according to clinical presentation and physician/patient preference. PREDICTORS Presentation with flash pulmonary edema (n = 37 [7.8%]), refractory hypertension (n = 116 [24.3%]), or rapidly declining kidney function (n = 46 [9.7%]) compared to low-risk presentation with none of these phenotypes (n = 230 [49%]). Percutaneous revascularization (performed in 32% of flash pulmonary edema, 28% of rapidly declining kidney function, and 28% of refractory hypertension patients) compared to medical management. OUTCOMES Death, cardiovascular (CV) event, end-stage kidney disease. RESULTS During a median follow-up of 3.8 (IQR, 1.8-5.8) years, 55% died, 33% had a CV event, and 18% reached end-stage kidney disease. In medically treated patients, flash pulmonary edema was associated with increased risk of death (HR, 2.2; 95% CI, 1.4-3.5; P < 0.001) and CV event (HR, 3.1; 95% CI, 1.7-5.5; P < 0.001), but not end-stage kidney disease, compared to the low-risk phenotype. No increased risk for any end point was observed in patients presenting with rapidly declining kidney function or refractory hypertension. Compared to medical treatment, revascularization was associated with reduced risk for death (HR, 0.4; 95% CI, 0.2-0.9; P = 0.01), but not CV event or end-stage kidney disease, in patients presenting with flash pulmonary edema. Revascularization was not associated significantly with reduced risk for any end point in rapidly declining kidney function or refractory hypertension. When these presentations were present in combination (n = 31), revascularization was associated with reduced risk for death (HR, 0.15; 95% CI, 0.02-0.9; P = 0.04) and CV event (HR, 0.23; 95% CI, 0.1-0.6; P = 0.02). LIMITATIONS Observational study; retrospective analysis; potential treatment bias. CONCLUSIONS This analysis supports guidelines citing flash pulmonary edema as an indication for renal artery revascularization in atherosclerotic renovascular disease. Patients presenting with a combination of rapidly declining kidney function and refractory hypertension also may benefit from revascularization and may represent a subgroup worthy of further investigation in more robust trials.

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.

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 years 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.

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.

Gadolinium‐enhanced magnetic resonance imaging for renovascular disease and nephrogenic systemic fibrosis: Critical review of the literature and UK experience

To examine the positive reporting bias regarding the link with gadolinium (Gd) exposure and nephrogenic systemic fibrosis (NSF) in patients with renal impairment. This link has impacted strongly the international radiology safety guidelines. We believe that positive reporting bias has prevailed in the literature and that very few patients with a glomerular filtration rate (GFR) 15–29 mL/min (stage 4 chronic kidney disease [CKD]) should be regarded as high risk.

Low Risk for Nephrogenic Systemic Fibrosis in Nondialysis Patients Who Have Chronic Kidney Disease and Are Investigated with Gadolinium-Enhanced Magnetic Resonance Imaging

BACKGROUND AND OBJECTIVES During the past decade, nephrogenic systemic fibrosis (NSF) has been reported in patients who have severe renal impairment and have been exposed to a gadolinium (Gd)-based contrast agent during magnetic resonance imaging (MRI). As a result of positive reporting bias, many suitable patients with chronic kidney disease (CKD) are being denied a highly important form of investigation that can be safely undertaken. We analyzed the safety of Gd-MRI in patients with CKD and varying levels of estimated GFR (eGFR). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We performed a retrospective analysis of 2053 unselected patients who had CKD and had received Gd-MRI between 1999 and 2009, so as to determine the risk for NSF related to level of CKD, nature of Gd preparation, and Gd dosage. RESULTS Overall, 2053 patients (63.5% men; mean age 60.6 +/- 15.7 years) had 2278 Gd-MRI scans; their mean eGFR was 40.7 +/- 23.7 ml/min. A total of 918 (44.7%) patients had stage 3, 491 (23.9%) had stage 4, and 117 (5.7%) had predialysis stage 5 CKD. No cases of NSF were identified during an average follow-up period of 28.6 +/- 18.2 months. CONCLUSIONS In this study, no patients developed NSF during extended follow-up, even after multiple Gd doses in some. Gd-MRI can be safely undertaken in the majority of patients with CKD, but caution is merited for dialysis patients and those with acute kidney injury, with relative caution for predialysis patients with stage 5 CKD.

Prediction and assessment of responses to renal artery revascularization with dynamic contrast-enhanced magnetic resonance imaging: a pilot study

The aim of this study was to assess the potential of dynamic contrast-enhanced (DCE) MRI to predict and evaluate functional outcomes after renal artery revascularization for renal artery stenosis (RAS). The single-kidney glomerular filtration rate (SK-GFR) was measured in 15 patients with atherosclerotic RAS with DCE-MRI and radioisotopes at baseline and 4 mo after revascularization. DCE-MRI also produced measurements of blood flow, blood volume, extraction fraction, tubular transit time, and functional volume. Stented kidneys (n = 22) were divided into three response groups on the basis of the changes in radioisotope SK-GFR: improved (n = 5), stable (n = 13), and deteriorated (n = 4). A good agreement was found between SK-GFR values from DCE-MRI and radioisotopes (correlation coefficient: 0.91). Before intervention, kidneys that improved had lower extraction fraction, higher blood volume, longer tubular transit time, and lower SK-GFR. After intervention, improved kidneys had increased functional volume, and deteriorated kidneys had reduced functional volume and extraction fraction. Revascularization improved blood flow and blood volume in all groups. This pilot study led to the hypothesis that well-vascularized kidneys with reduced extraction fractions are most likely to benefit from revascularization. More generally, DCE-MRI has the potential to replace radioisotope measurement of SK-GFR and may improve patient management by providing additional information on tissue perfusion.

Current Management of Atherosclerotic Renovascular Disease – What Have We Learned from ASTRAL?

With an increasingly ageing and atherosclerotic-prone population, clinical encounters with patients with atheromatous renovascular disease (ARVD) are commonplace. ARVD is frequently associated with chronic kidney disease (CKD) and hypertension, but evidence suggests that causality only occurs in the minority and it is likely that many atherosclerotic renal artery stenosis (RAS) lesions are incidental. Its association with extensive cardiovascular co-morbidity predisposes to a high patient mortality. The availability of renal angioplasty and stenting, which are generally safe techniques for dilating RAS lesions, has led to widespread use of these endovascular therapies in ARVD, but the outcomes after treatment have been inconsistent, with no clear evidence of benefit in many patients. There has been a great need for a large and appropriately powered randomised control trial to help guide clinical practice. In this review, we present an interpretation of the results of the recently reported Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial as well as a brief review of the latest literature, so as to provide the latest guidance regarding the management of this common condition.