Diana Vassallo

Three Decades of Atherosclerotic Reno-vascular Disease Management - Changing Outcomes in an Observational Study.

Background/Aims: Optimized medical therapy has improved cardiovascular outcomes in the general population. To investigate whether changes in the management of atherosclerotic renovascular disease (ARVD) have had an impact on clinical outcomes. Methods: Recruitment into this single-center prospective cohort study started in 1986. Data was analyzed retrospectively. Patients were divided into four groups based on relationship of diagnosis year to landmark randomized controlled trials (RCT); group 1 - pre-large RCT data (1986-2000); group 2 - post-early RCT (2001-2004); group 3 - ASTRAL study recruitment era (2004-2009); group 4 - post-ASTRAL (2009-2014). Results: In total, 872 patients were followed for a median 54.9 months (IQR 20.2-96.2). Over successive time-periods, there was an increase in baseline utilization of renin angiotensin blockade (RAB) (group 4: 69% vs. group 1: 31%, p<0.001), statins (74% vs 20%, p<0.001) and beta-blockers (43% vs 30%, p=0.024). Median time to death, end-stage kidney disease and cardiovascular events improved except in group 4, which displayed more baseline cardiovascular comorbidities. The number of investigative angiograms performed decreased from 139 per year between 2006 and 2008 to 74 per year in group 4. Conclusions: Although fewer patients are being investigated for ARVD in our center, these have more cardiovascular comorbidities. Nonetheless, optimized medical therapy may have contributed towards improved proteinuria, renal function and clinical outcomes in patients diagnosed with ARVD.

From anatomy to function: diagnosis of atherosclerotic renal artery stenosis

Atherosclerotic renal artery stenosis (ARAS) affects 7% of the over 65 s and will be increasingly common with an ageing population. ARAS obstructs normal renal perfusion with adverse renal and cardiovascular consequences. Drug therapy is directed at reducing atherosclerotic risk. Two recent major trials of revascularization for ARAS showed that clinical outcomes were not improved beyond those offered by optimal drug therapy in most patients. This reflects experimental data showing that restoration of blood flow alone may not attenuate a cascade of tissue injury. A shift from anatomic to functional imaging of ARAS coupled to novel therapies might improve clinical outcomes in selected patients. This review outlines the case for separately assessing hemodynamic significance of arterial stenosis and functional reserve of renal parenchymal tissue. The authors consider current and emerging diagnostic techniques for ARAS and their potential to allow individualized and functionally directed treatments.

Respiratory manifestations of anca-associated vasculitis.

The prevalence of pulmonary manifestations of ANCA‐associated vasculitis (AAV) is not well understood. This study describes the prevalence of respiratory complications of AAV detected via imaging in patients presenting to a secondary renal centre and describes the associations with mortality.

Progress in the treatment of atherosclerotic renovascular disease: the conceptual journey and the unanswered questions

Over the past decades, management of atherosclerotic renovascular disease (ARVD) has undergone significant progress, in parallel with increased knowledge about the complex pathophysiology of this condition. Modern multi-targeted medical management of atherosclerosis has driven a change in both the natural history and the clinical outcomes of ARVD. Progression to total renal artery occlusion is a much less common occurrence and while early studies have reported that up to 41% of patients reached renal end-points over a mean follow-up of 44 months, the latest randomized controlled trials have shown that progressive renal impairment occurs in 16-22% of patients, with <8% of patients reaching end-stage kidney disease (ESKD) over a similar time-frame. However, the results of the latest large ARVD trials investigating the effect of renal stenting upon clinical outcomes have been influenced by selection bias as high-risk patients with clinically significant renal artery stenosis (RAS) have largely been excluded from these studies. Although the neutral results of these trials have shown uncertainty about the role of revascularization in the management of patients with ARVD, there is evidence that revascularization can optimize outcomes in selected patients with a high-risk clinical phenotype. Future challenges lie in identifying important subgroups of patients with critical RAS and viable kidneys, while continuing to develop strategies to protect the renal parenchyma and hence improve clinical outcomes.

Hepatitis e infection in a renal transplant recipient.

An asymptomatic 35-year-old renal transplant recipient was noted to have deranged liver function tests. Liver biopsy revealed a portal inflammatory process with mild lobular activity and portal fibrous expansion, consistent with a virally mediated process. An extensive viral screen confirmed infection with Hepatitis E virus genotype 3 (HEV-3). There is increased awareness about locally acquired Hepatitis E virus (HEV) infection in the transplant population in the UK. The important implications of this infection are becoming more apparent as progression to liver cirrhosis can occur. However, the incidence, natural history, and treatment of HEV infection in the transplant population are not well established. This report illustrates a case of delayed spontaneous clearance of the HEV infection.

Design of a clinical risk calculator for major clinical outcomes in patients with atherosclerotic renovascular disease

Background Risk stratification in atherosclerotic renovascular disease (ARVD) can influence treatment decisions and facilitate patient selection for revascularization. In this study, we aim to use variables with the best predictive value to design a risk calculator that can assist clinicians with risk stratification and outcome prediction. Methods Patients with a radiological diagnosis of ARVD referred to our tertiary renal centre were recruited into this prospective cohort study between 1986 and 2014. Primary clinical endpoints included: death, progression to end-stage kidney disease and cardiovascular events (CVE). A stepwise regression model was used to select variables with the most significant hazard ratio for each clinical endpoint. The risk calculator was designed using Hypertext Markup Language. Survival and CVE-free survival were estimated at 1, 5 and 10 years. Results In total, 872 patients were recruited into the Salford ARVD study with a median follow-up period of 54.9 months (interquartile range 20.2-96.0). Only models predicting death and CVE showed good performance (C-index >0.80). Survival probabilities obtained from the risk calculator show that most patients with ARVD have reduced long-term survival. Revascularization improved outcomes in patients with higher baseline estimated glomerular filtration rate and lower proteinuria but not in those with co-existing comorbidities and higher levels of baseline proteinuria. Conclusions Although this risk calculator requires further independent validation in other ARVD cohorts, this study shows that a small number of easily obtained variables can help predict clinical outcomes and encourage a patient-specific therapeutic approach.

The Cardiac Impact of Atherosclerotic Renovascular Disease (ARVD)

Atherosclerotic renovascular disease (ARVD) typically occurs in the context of systemic atherosclerosis, hence patients with this condition usually have a high burden of coronary artery disease. In addition, neurohormonal stimulation driven by renin–angiotensin aldosterone system activation, chronic hypertension, and renal impairment can lead to cardiac remodeling. One-third of patients with ARVD have symptoms consistent with chronic heart failure while around 10% present with acute decompensated heart failure or flash pulmonary edema. Echocardiographic studies have shown that up to half of patients with ARVD have evidence of concentric hypertrophy caused by an increase in cardiac afterload; this can progress to diastolic heart failure, characterized by preserved ejection fraction. Tight risk factor control and multi-targeted vascular protective therapy consisting of renin–angiotensin blockade, statins, and anti-platelets agents are essential to mitigate the high risk of adverse cardiovascular events in these patients. While large randomized controlled trials have not shown that revascularization confers any added benefit to patients with ARVD, these studies have been criticized for specifically excluding patients presenting with high-risk features such as decompensated cardiac syndromes (recurrent chronic heart failure, flash pulmonary edema or unstable angina), uncontrolled hypertension or rapidly deteriorating renal function. Several observational studies suggest that renal revascularization may be of benefit in the minority proportion of patients with these features, especially those presenting with flash pulmonary edema. Further research is required to help identify these patients accurately and ensure timely referral for revascularization.

Atherosclerotic renovascular disease – epidemiology, treatment and current challenges

The neutral results of recent large randomized controlled trials comparing renal revascularization with optimal medical therapy in patients with atherosclerotic renovascular disease (ARVD) have cast doubt on the role of revascularization in the management of unselected patients with this condition. However, these studies have strengthened the evidence base for the role of contemporary intensive medical vascular protection therapy and aggressive risk factor control in improving clinical outcomes in ARVD. Patients presenting with ‘high-risk’ clinical features such as uncontrolled hypertension, rapidly declining renal function or flash pulmonary oedema are underrepresented in these studies; hence these results may not be applicable to all patients with ARVD. In this ‘high-risk’ subgroup, conservative management may not be sufficient in preventing adverse events, and indeed, observational evidence suggests that this specific patient subgroup may gain benefit from timely renal revascularization. Current challenges include the development of novel diagnostic techniques to establish haemodynamic significance of a stenosis, patient risk stratification and prediction of post-revascularization outcomes to ultimately facilitate patient selection for revascularization. In this paper we describe the epidemiology of this condition and discuss treatment recommendations for this condition in light of the results of recent randomized controlled trials while highlighting important clinical unmet needs and challenges faced by clinicians managing this condition.

Myosin heavy chain-9-related disorders (MYH9-RD): a case report

Myosin heavy chain-9-related disorders (MYH9-RDs) are a group of autosomal-dominant disorders caused by mutations in the MYH9 gene. The features include congenital macrothrombocytopaenia, inclusion bodies in neutrophils and a variable risk of developing sensorineural deafness, progressive renal impairment and presenile cataracts. A 44-year-old Caucasian man was initially thought to have Alports syndrome and thrombocytopaenia secondary to idiopathic thrombocytopaenic purpura (ITP). A detailed family history and genetic analysis revealed a diagnosis of MYH9-RD. This case highlights the implications of a delayed diagnosis and the ongoing challenges encountered during management of individuals with this condition.