Matthew P.M. Graham-Brown

The Evolution of the Journal Club: From Osler to Twitter

Journal clubs have typically been held within the walls of academic institutions and in medicine have served the dual purpose of fostering critical appraisal of literature and disseminating new findings. In the last decade and especially the last few years, online and virtual journal clubs have been started and are flourishing, especially those harnessing the advantages of social media tools and customs. This article reviews the history and recent innovations of journal clubs. In addition, the authors describe their experience developing and implementing NephJC, an online nephrology journal club conducted on Twitter.

The Potential Cardiovascular Benefits of Low-Glucose Degradation Product, Biocompatible Peritoneal Dialysis Fluids: A Review of the Literature.

Cardiovascular mortality in the end-stage renal disease (ESRD) population remains the leading cause of death. Targeting traditional cardiovascular risk factors has proven unsuccessful in this patient population, and therefore attention has turned to risk factors related to chronic kidney disease (CKD). The toxicity of high-glucose peritoneal dialysis (PD) solutions has been well documented. The breakdown of glucose into glucose degradation products (GDP) and advanced glycation end-products (AGE) has the ability to alter cell viability and cause premature apoptosis and is strongly correlated with interstitial fibrosis and microvascular sclerosis. Biocompatible solutions have been introduced to combat the hostile milieu to which PD patients are exposed. Given the considerable cardiovascular burden for PD patients, little is known about the cardiovascular impact the new biocompatible solutions may have. This review analyzes the existing literature regarding the mechanisms through which low-GDP solutions may modulate cardiovascular risk. Interventions using low-GDP solutions have provided encouraging changes in structural cardiovascular measures such as left ventricular mass (LVM), although metabolic changes from reduced GDP and AGE exposure yield inconclusive results on vascular remodelling. It is thought that the local effects of reduced glucose exposure may improve membrane integrity and therefore fluid status. Further research in the form of a robust randomized controlled trial should be carried out to assess the true extent of the cardiovascular benefits these biocompatible solutions may hold.

Intestinal Barrier Disturbances in Haemodialysis Patients: Mechanisms, Consequences, and Therapeutic Options

There is accumulating evidence that the intestinal barrier and the microbiota may play a role in the systemic inflammation present in HD patients. HD patients are subject to a number of unique factors, some related to the HD process and others simply to the uraemic milieu but with common characteristic that they can both alter the intestinal barrier and the microbiota. This review is intended to provide an overview of the current methods for measuring such changes in HD patients, the mechanisms behind these changes, and potential strategies that may mitigate these modifications. Lastly, intradialytic exercise is an increasingly employed intervention in HD patients; however the potential implications that this may have for the intestinal barrier are not known; therefore future research directions are also covered.

A 4-month programme of in-centre nocturnal haemodialysis was associated with improvements in patient outcomes.

Background Extended periods of haemodialysis (HD) can improve patient outcomes. In-centre nocturnal haemodialysis (INHD) should be explored as a method of offering extended periods of HD to patients unsuitable for or unable to perform home therapy. Methods Ten self-selecting, prevalent HD patients started an INHD programme to assess feasibility and patient satisfaction. Quality-of-life (QOL) measures were evaluated at enrolment and after 4 months of INHD using the EQ-5D, the Hospital Anxiety and Depression Scale (HADS) and the SF-12 questionnaires. Demographic, biochemical and haematological data and data on dialysis adequacy were collected before starting INHD and after 4 months. Results Three of the 10 patients failed to complete the 2-week run-in period. Seven patients completed the 4-month programme, with mean dialysis time of 355 ± 43.92 min throughout the period. The EQ-5D visual analogue score improved from 48 ± 16.89 to 72 ± 13.2 (P = 0.003) and the HADS anxiety score decreased from 9 ± 5.83 to 3.57 ± 3.04 (P = 0.029). The urea reduction ratio improved from 71.57 ± 2.29% to 80.43 ± 3.101% (P < 0.001), with improvements in phosphate control, reducing to within the target range from 1.73 ± 0.6 to 1.2 ± 0.2 (P = 0.08). Ultrafiltration (UF) volumes increased during the study from 2000 ± 510 to 2606 ± 343 mL (P = 0.015); there was a significant reduction in mean UF rate adjusted for body weight from 6.47 ± 1.71 to 4.61 ± 1.59 mL/kg/h (P = 0.032). Sensitivity analyses confirmed the significance of these results. Conclusions This single-centre study showed a 4-month programme of extended hours INHD is safe and associated with improvements in QOL measures, decreased UF rates and measures of dialysis adequacy. These data have been used to expand our service and inform the design of future randomized controlled trials to examine medical endpoints.

Imaging of Myocardial Fibrosis in Patients with End-Stage Renal Disease: Current Limitations and Future Possibilities.

Cardiovascular disease in patients with end-stage renal disease (ESRD) is driven by a different set of processes than in the general population. These processes lead to pathological changes in cardiac structure and function that include the development of left ventricular hypertrophy and left ventricular dilatation and the development of myocardial fibrosis. Reduction in left ventricular hypertrophy has been the established goal of many interventional trials in patients with chronic kidney disease, but a recent systematic review has questioned whether reduction of left ventricular hypertrophy improves cardiovascular mortality as previously thought. The development of novel imaging biomarkers that link to cardiovascular outcomes and that are specific to the disease processes in ESRD is therefore required. Postmortem studies of patients with ESRD on hemodialysis have shown that the extent of myocardial fibrosis is strongly linked to cardiovascular death and accurate imaging of myocardial fibrosis would be an attractive target as an imaging biomarker. In this article we will discuss the current imaging methods available to measure myocardial fibrosis in patients with ESRD, the reliability of the techniques, specific challenges and important limitations in patients with ESRD, and how to further develop the techniques we have so they are sufficiently robust for use in future clinical trials.

The use of T1 mapping to define myocardial fibrosis in haemodialysis patients

Haemodialysis (HD) patients show high levels of fibrosis on myocardial biopsy, similar to that seen in dilated cardiomyopathy, which is associated with an increased risk of sudden cardiac death. The use of intravenous gadolinium to detect myocardial fibrosis during cardiac magnetic resonance imaging (CMR) is contraindicated in HD patients due to the rare complication of nephrogenic systemic fibrosis. Native T1 mapping may be an alternative method of measuring myocardial fibrosis in HD patients that …

The importance of accurate measurement of aortic stiffness in patients with chronic kidney disease and end-stage renal disease

Abstract Cardiovascular (CV) disease is the leading cause of death in chronic kidney disease (CKD) and end-stage renal disease (ESRD). A key driver in this pathology is increased aortic stiffness, which is a strong, independent predictor of CV mortality in this population. Aortic stiffening is a potentially modifiable biomarker of CV dysfunction and in risk stratification for patients with CKD and ESRD. Previous work has suggested that therapeutic modification of aortic stiffness may ameliorate CV mortality. Nevertheless, future clinical implementation relies on the ability to accurately and reliably quantify stiffness in renal disease. Pulse wave velocity (PWV) is an indirect measure of stiffness and is the accepted standard for non-invasive assessment of aortic stiffness. It has typically been measured using techniques such as applanation tonometry, which is easy to use but hindered by issues such as the inability to visualize the aorta. Advances in cardiac magnetic resonance imaging now allow direct measurement of stiffness, using aortic distensibility, in addition to PWV. These techniques allow measurement of aortic stiffness locally and are obtainable as part of a comprehensive, multiparametric CV assessment. The evidence cannot yet provide a definitive answer regarding which technique or parameter can be considered superior. This review discusses the advantages and limitations of non-invasive methods that have been used to assess aortic stiffness, the key studies that have assessed aortic stiffness in patients with renal disease and why these tools should be standardized for use in clinical trial work.

Induction treatment of previously undiagnosed ANCA-associated vasculitis in a renal transplant patient with Rituximab.

We report the case of a 40-year-old female transplant patient with undiagnosed ANCA-associated vasculitis (AAV) and renal allograft dysfunction who achieved disease remission with restoration of transplant function following induction therapy with rituximab. There are currently no trial data looking at the use of rituximab for induction of remission of renal transplant patients with AAV. Although recurrence of AAV following renal transplantation is rare, such patients have invariably had multiple previous exposures to induction and maintenance immunosuppressive regimens, often limiting treatment options post-transplantation. In this case, rituximab was well tolerated with no side effects, and was successful in salvaging transplant function. Optimal treatment regimens for relapsed AAV in the transplant population are not known, and clinical trials are needed to evaluate the efficacy and safety of rituximab at inducing and maintaining disease remission in relapsed AAV following transplantation.

T1 Mapping in Athletes: A Novel Tool to Differentiate Physiological Adaptation From Pathology?

Cardiac adaptation to high-intensity exercise is well recognized and often termed the athlete’s heart. The characteristic features of athlete’s heart are increased left ventricular (LV) volume, increased LV wall thickness and mass, resting bradycardia, and ECG repolarization abnormalities.1 These changes are particularly associated with endurance training causing eccentric LV hypertrophy, whereas significant resistance training (eg, weight lifters) may lead to concentric LV hypertrophy. Although somewhat controversial, it is widely accepted that in the majority of athletes, these changes occur as a physiological response to exercise training; LV volumes and mass regress in subjects who stop training and decondition.2 However, there is an increasing number of reports in older veteran athletes that may suggest that some people who exercise intensely over many years develop myocardial fibrosis3 and have an increased risk of arrhythmias, particularly atrial fibrillation.4 See Article by McDiarmid et al Difficulties may also arise in differentiating athlete’s heart from pathological cardiac conditions that are associated with sudden death, such as dilated and hypertrophic cardiomyopathy (HCM),5 in certain situations. Many countries and professional sports teams have implemented preparticipation sports screening programs, and because of the high prevalence of ECG abnormalities, a significant minority of athletes are referred for echocardiographic imaging. Similarly, healthy athletes with atypical cardiac symptoms are more likely to be referred for cardiac investigations because of high frequency of repolarization abnormalities. Cardiac magnetic resonance imaging (CMR) may be particularly useful in such situations because of the superiority over echocardiography to detect hypertrophy in the lateral segments and apical HCM.6 Another major strength of CMR is the …

Investigating the effects of 6 months extended duration, in-centre nocturnal versus conventional haemodialysis treatment: a non-randomised, controlled feasibility study

Introduction In-centre nocturnal haemodialysis (INHD) is an underutilised dialysis regimen that can potentially provide patients with better clinical outcomes due to extended treatment times. We have established an INHD programme within our clinical network, fulfilling a previously unmet patient need. This feasibility study aims to gather sufficient data on numerous outcome measures to inform the design of a multicentre randomised controlled trial that will establish the potential benefits of INHD and increase the availability of this service nationally and internationally. Methods and analysis This will be a non-randomised controlled study. Prevalent patients on haemodialysis (HD) will electively change from a conventional in-centre HD regimen of 4 hours thrice weekly to a regimen of extended treatment times (5–8 hours) delivered in-centre overnight thrice weekly. After recruitment of the INHD cohort, a group of patients matched for age, gender and dialysis vintage will be selected from patients remaining on a conventional daytime dialysis programme. Outcome measures will include left ventricular mass as measured by MRI, physical performance measured by the short physical performance battery and physical activity measured by accelerometry. Additionally we will measure quality of life using validated questionnaires, nutritional status by bioimpedance spectroscopy and food diaries, and blood sampling for markers of cardiovascular disease, systemic inflammation. Suitable statistical tests shall be used to analyse the data. We will use omnibus tests to observe changes over the duration of the intervention and between groups. We will also look for associations between outcome measures that may warrant further investigation. These data will be used to inform the power calculation for future studies. Ethics and dissemination A favourable opinion was granted by Northampton Research Ethics Committee (15/EM/0268). It is anticipated that results of this study will be presented at national and international meetings, with reports being published in journals during 2017. Trial registration number ISRCTN16672784.