Renal Association Clinical Practice Guideline on Haemodialysis

© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This guideline is written primarily for doctors and nurses working in dialysis units and related areas of medicine in the UK, and is an update of a previous version written in 2009. It aims to provide guidance on how to look after patients and how to run dialysis units, and provides standards which units should in general aim to achieve. We would not advise patients to interpret the guideline as a rulebook, but perhaps to answer the question: "what does good quality haemodialysis look like?"The guideline is split into sections: each begins with a few statements which are graded by strength (1 is a firm recommendation, 2 is more like a sensible suggestion), and the type of research available to back up the statement, ranging from A (good quality trials so we are pretty sure this is right) to D (more like the opinion of experts than known for sure). After the statements there is a short summary explaining why we think this, often including a discussion of some of the most helpful research. There is then a list of the most important medical articles so that you can read further if you want to - most of this is freely available online, at least in summary form.A few notes on the individual sections: 1. This section is about how much dialysis a patient should have. The effectiveness of dialysis varies between patients because of differences in body size and age etc., so different people need different amounts, and this section gives guidance on what defines "enough" dialysis and how to make sure each person is getting that. Quite a bit of this section is very technical, for example, the term "eKt/V" is often used: this is a calculation based on blood tests before and after dialysis, which measures the effectiveness of a single dialysis session in a particular patient. 2. This section deals with "non-standard" dialysis, which basically means anything other than 3 times per week. For example, a few people need 4 or more sessions per week to keep healthy, and some people are fine with only 2 sessions per week - this is usually people who are older, or those who have only just started dialysis. Special considerations for children and pregnant patients are also covered here. 3. This section deals with membranes (the type of "filter" used in the dialysis machine) and "HDF" (haemodiafiltration) which is a more complex kind of dialysis which some doctors think is better. Studies are still being done, but at the moment we think it's as good as but not better than regular dialysis. 4. This section deals with fluid removal during dialysis sessions: how to remove enough fluid without causing cramps and low blood pressure. Amongst other recommendations we advise close collaboration with patients over this. 5. This section deals with dialysate, which is the fluid used to "pull" toxins out of the blood (it is sometimes called the "bath"). The level of things like potassium in the dialysate is important, otherwise too much or too little may be removed. There is a section on dialysate buffer (bicarbonate) and also a section on phosphate, which occasionally needs to be added into the dialysate. 6. This section is about anticoagulation (blood thinning) which is needed to stop the circuit from clotting, but sometimes causes side effects. 7. This section is about certain safety aspects of dialysis, not seeking to replace well-established local protocols, but focussing on just a few where we thought some national-level guidance would be useful. 8. This section draws together a few aspects of dialysis which don't easily fit elsewhere, and which impact on how dialysis feels to patients, rather than the medical outcome, though of course these are linked. This is where home haemodialysis and exercise are covered. There is an appendix at the end which covers a few aspects in more detail, especially the mathematical ideas. Several aspects of dialysis are not included in this guideline since they are covered elsewhere, often because they are aspects which affect non-dialysis patients too. This includes: anaemia, calcium and bone health, high blood pressure, nutrition, infection control, vascular access, transplant planning, and when dialysis should be started.Peer reviewe

Ly6cLo non-classical monocytes promote resolution of rhesus rotavirus-mediated perinatal hepatic infammation

Perinatal hepatic inflammation can have devastating consequences. Monocytes play an important role in the initiation and resolution of inflammation, and their diverse functions can be attributed to specific cellular subsets: pro-inflammatory or classical monocytes (Ly6c(Hi)) and pro-reparative or non-classical monocytes (Ly6c(Lo)). We hypothesized that inherent differences in Ly6c(Hi) classical monocytes and Ly6c(Lo) non-classical monocytes determine susceptibility to perinatal hepatic inflammation in late gestation fetuses and neonates. We found an anti-inflammatory transcriptional profile expressed by Ly6c(Lo) non-classical monocytes, and a physiologic abundance of these cells in the late gestation fetal liver. Unlike neonatal pups, late gestation fetuses proved to be resistant to rhesus rotavirus (RRV) mediated liver inflammation. Furthermore, neonatal pups were rendered resistant to RRV-mediated liver injury when Ly6c(Lo) non-classical monocytes were expanded. Pharmacologic inhibition of Ly6c(Lo) non-classical monocytes in this setting restored susceptibility to RRV-mediated disease. These data demonstrate that Ly6c(Lo) monocytes promote resolution of perinatal liver inflammation in the late gestation fetus, where there is a physiologic expansion of non-classical monocytes, and in the neonatal liver upon experimental expansion of these cells. Therapeutic strategies directed towards enhancing Ly6c(Lo) non-classical monocyte function may mitigate the detrimental effects of perinatal liver inflammation

Activating Transcription Factor 3 Promotes Loss of the Acinar Cell Phenotype in Response to Cerulein-Induced Pancreatitis in Mice

Pancreatitis is a debilitating disease of the exocrine pancreas that, under chronic conditions, is a major susceptibility factor for pancreatic ductal adenocarcinoma (PDAC). Although down-regulation of genes that promote the mature acinar cell fate is required to reduce injury associated with pancreatitis, the factors that promote this repression are unknown. Activating transcription factor 3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly activated during pancreatic insult. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that ATF3 is bound to the transcriptional regulatory regions of \u3e30% of differentially expressed genes during the initiation of pancreatitis. Of importance, ATF3-dependent regulation of these genes was observed only upon induction of pancreatitis, with pathways involved in inflammation, acinar cell differentiation, and cell junctions being specifically targeted. Characterizing expression of transcription factors that affect acinar cell differentiation suggested that acinar cells lacking ATF3 maintain a mature cell phenotype during pancreatitis, a finding supported by maintenance of junctional proteins and polarity markers. As a result

Regular breakfast consumption and type 2 diabetes risk markers in 9- to 10-year-old children in the child heart and health study in England (CHASE): a cross-sectional analysis.

BACKGROUND: Regular breakfast consumption may protect against type 2 diabetes risk in adults but little is known about its influence on type 2 diabetes risk markers in children. We investigated the associations between breakfast consumption (frequency and content) and risk markers for type 2 diabetes (particularly insulin resistance and glycaemia) and cardiovascular disease in children. METHODS AND FINDINGS: We conducted a cross-sectional study of 4,116 UK primary school children aged 9-10 years. Participants provided information on breakfast frequency, had measurements of body composition, and gave fasting blood samples for measurements of blood lipids, insulin, glucose, and glycated haemoglobin (HbA1c). A subgroup of 2,004 children also completed a 24-hour dietary recall. Among 4,116 children studied, 3,056 (74%) ate breakfast daily, 450 (11%) most days, 372 (9%) some days, and 238 (6%) not usually. Graded associations between breakfast frequency and risk markers were observed; children who reported not usually having breakfast had higher fasting insulin (percent difference 26.4%, 95% CI 16.6%-37.0%), insulin resistance (percent difference 26.7%, 95% CI 17.0%-37.2%), HbA1c (percent difference 1.2%, 95% CI 0.4%-2.0%), glucose (percent difference 1.0%, 95% CI 0.0%-2.0%), and urate (percent difference 6%, 95% CI 3%-10%) than those who reported having breakfast daily; these differences were little affected by adjustment for adiposity, socioeconomic status, and physical activity levels. When the higher levels of triglyceride, systolic blood pressure, and C-reactive protein for those who usually did not eat breakfast relative to those who ate breakfast daily were adjusted for adiposity, the differences were no longer significant. Children eating a high fibre cereal breakfast had lower insulin resistance than those eating other breakfast types (p for heterogeneity <0.01). Differences in nutrient intakes between breakfast frequency groups did not account for the differences in type 2 diabetes markers. CONCLUSIONS: Children who ate breakfast daily, particularly a high fibre cereal breakfast, had a more favourable type 2 diabetes risk profile. Trials are needed to quantify the protective effect of breakfast on emerging type 2 diabetes risk. Please see later in the article for the Editors' Summary

Genetic markers of Restless Legs Syndrome in Parkinson disease

INTRODUCTION: Several studies proposed that Restless Legs Syndrome (RLS) and Parkinson disease (PD) may be clinically and/or etiologically related. To examine this hypothesis, we aimed to determine whether the known RLS genetic markers may be associated with PD risk, as well as with PD subtype. METHODS: Two case-control cohorts from Tel-Aviv and New-York, including 1133 PD patients and 867 controls were genotyped for four RLS-related SNPs in the genes MEIS1, BTBD9, PTPRD and MAP2K5/SKOR1. The association between genotype, PD risk and phenotype was tested using multivariate regression models. RESULTS: None of the tested SNPs was significantly associated with PD risk, neither in any individual cohort nor in the combined analysis after correction for multiple comparisons. The MAP2K5/SKOR1 marker rs12593813 was associated with higher frequency of tremor in the Tel-Aviv cohort (61.0% vs. 46.5%, p = 0.001, dominant model). However, the risk allele for tremor in this gene has been associated with reduced RLS risk. Moreover, this association did not replicate in Tremor-dominant PD patients from New-York. CONCLUSION: RLS genetic risk markers are not associated with increased PD risk or subtype in the current study. Together with previous genetic, neuropathological and epidemiologic studies, our results further strengthen the notion that RLS and PD are likely to be distinct entities

Characteristics of outdoor falls among older people: A qualitative study

Background Falls are a major threat to older people’s health and wellbeing. Approximately half of falls occur in outdoor environments but little is known about the circumstances in which they occur. We conducted a qualitative study to explore older people’s experiences of outdoor falls to develop understanding of how they may be prevented. Methods We conducted nine focus groups across the UK (England, Wales, and Scotland). Our sample was from urban and rural settings and different environmental landscapes. Participants were aged 65+ and had at least one outdoor fall in the past year. We analysed the data using framework and content analyses. Results Forty-four adults aged 65 – 92 took part and reported their experience of 88 outdoor falls. Outdoor falls occurred in a variety of contexts, though reports suggested the following scenarios may have been more frequent: when crossing a road, in a familiar area, when bystanders were around, and with an unreported or unknown attribution. Most frequently, falls resulted in either minor or moderate injury, feeling embarrassed at the time of the fall, and anxiety about falling again. Ten falls resulted in fracture, but no strong pattern emerged in regard to the contexts of these falls. Anxiety about falling again appeared more prevalent among those that fell in urban settings and who made more visits into their neighbourhood in a typical week. Conclusions This exploratory study has highlighted several aspects of the outdoor environment that may represent risk factors for outdoor falls and associated fear of falling. Health professionals are recommended to consider outdoor environments as well as the home setting when working to prevent falls and increase mobility among older people

Endothelial Dysfunction and Specific Inflammation in Obesity Hypoventilation Syndrome

BACKGROUND: Obesity hypoventilation syndrome (OHS) is associated with increased cardiovascular morbidity. What moderate chronic hypoventilation adds to obesity on systemic inflammation and endothelial dysfunction remains unknown. QUESTION: To compare inflammatory status and endothelial function in OHS versus eucapnic obese patients. METHODOLOGY: 14 OHS and 39 eucapnic obese patients matched for BMI and age were compared. Diurnal blood gazes, overnight polysomnography and endothelial function, measured by reactive hyperemia peripheral arterial tonometry (RH-PAT), were assessed. Inflammatory (Leptin, RANTES, MCP-1, IL-6, IL-8, TNFalpha, Resistin) and anti-inflammatory (adiponectin, IL-1Ra) cytokines were measured by multiplex beads immunoassays. PRINCIPAL FINDINGS: OHS exhibited a higher PaCO(2), a lower forced vital capacity (FVC) and tended to have a lower PaO(2) than eucapnic obese patients. (HS)-CRP, RANTES levels and glycated haemoglobin (HbA1c) were significantly increased in OHS (respectively 11.1+/-10.9 vs. 5.7+/-5.5 mg x l(-1) for (HS)-CRP, 55.9+/-55.3 vs 23.3+/-15.8 ng/ml for RANTES and 7.3+/-4.3 vs 6.1+/-1.7 for HbA1c). Serum adiponectin was reduced in OHS (7606+/-2977 vs 13,660+/-7854 ng/ml). Endothelial function was significantly more impaired in OHS (RH-PAT index: 0.22+/-0.06 vs 0.51+/-0.11). CONCLUSIONS: Compared to eucapnic obesity, OHS is associated with a specific increase in the pro-atherosclerotic RANTES chemokine, a decrease in the anti-inflammatory adipokine adiponectin and impaired endothelial function. These three conditions are known to be strongly associated with an increased cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT00603096

Insufficient antiretroviral therapy in pregnancy: missed opportunities for prevention of mother-to-child transmission of HIV in Europe

Background: Although mother-to-child transmission (MTCT) rates are at an all-time low in Western Europe, potentially preventable transmissions continue to occur. Duration of antenatal combination antiretroviral therapy (ART) is strongly associated with MTCT risk.Methods: Data on pregnant HIV-infected women enrolled in the Western and Central European sites of the European Collaborative Study between January 2000 and July 2009 were analysed. The proportion of women receiving no antenatal ART or 1-13 days of treatment was investigated, and associated factors explored using logistic regression models.Results: Of 2,148 women, 142 (7%) received no antenatal ART, decreasing from 8% in 2000-2003 to 5% in 2004-2009 (chi(2)=8.73; P= 14 days antenatal ART and 7.4% (10/136) among those with insufficient ART.Conclusions: Over the last 10 years, around one in 11 women in this study received insufficient antenatal ART, accounting for 40% of MTCTs. One-half of these women were diagnosed before conception, suggesting disengagement from care

The prognostic value of dobutamine stress echocardiography amongst British Indian Asian and Afro-Caribbean patients: a comparison with European white patients

Background The incidence of cardiovascular disease is considerably disparate among different racial and ethnic populations. While dobutamine stress echocardiography (DSE) has been shown to be useful in Caucasian patients, its role among ethnic minority groups remains unclear. This study aimed to investigate the prognostic importance of DSE in three ethnic groups in the UK. Methods DSE was performed on 6231 consecutive patients. After exclusions, 5329 patients formed the study (2676 [50.2 %] Indian Asian, 2219 [41.6 %] European white and 434 [8.1 %] Afro-Caribbean). Study outcome measures were non-fatal cardiac events (NFCE) and all-cause mortality. Results There were 849 (15.9 %) NFCE and 1365 (25.6 %) deaths over a median follow-up period of 4.6 years. In total 1174 (22 %) patients had inducible myocardial ischaemia during DSE, 859 (16.1 %) had fixed wall motion abnormalities and 3645 (68.4 %) patients had a normal study. Ethnicity did not predict events. Among the three ethnic groups, ischaemia on DSE was associated with 2 to 2.5 times the risk of non-fatal cardiac events and 1.2 to 1.4 times the risk of all-cause mortality. Peak wall motion score index was the strongest independent predictor of non-fatal cardiac events and all-cause mortality in all groups. The C statistic for the prediction of NFCE and all-cause mortality were significantly higher when DSE parameters were added to the standard risk factors for all ethnic groups. Conclusions DSE is a strong predictor of NFCE and all-cause mortality and provides predictive information beyond that provided by standard risk factors in three major racial and ethnic groups. No major differences among racial and ethnic groups in the predictive value of DSE was detected

Has Motivational Interviewing fallen into its own Premature Focus Trap?

Since the initial conception of the behaviour change method Motivational Interviewing, there has been a shift evident in epistemological, methodological and practical applications, from an inductive, process and practitioner-focussed approach to that which is more deductive, research-outcome, and confirmatory-focussed. This paper highlights the conceptual and practical problems of adopting this approach, including the consequences of assessing the what (deductive outcome-focussed) at the expense of the how (inductively process-focussed). We encourage a return to an inductive, practitioner and client-focussed MI approach and propose the use of Computer Assisted Qualitative Data Analysis Systems such as NVivo in research initiatives to support this aim