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Abstract Background Accurate predictions of animal occurrence in time and space are crucial for informing and implementing science-based management strategies for threatened species. Methods We compiled known, available satellite tracking data for pygmy blue whales in the Eastern Indian Ocean (n = 38), applied movement models to define low (foraging and reproduction) and high (migratory) move persistence underlying location estimates and matched these with environmental data. We then used machine learning models to identify the relationship between whale occurrence and environment, and predict foraging and migration habitat suitability in Australia and Southeast Asia. Results Our model predictions were validated by producing spatially varying accuracy metrics. We identified the shelf off the Bonney Coast, Great Australian Bight, and southern Western Australia as well as the slope off the Western Australian coast as suitable habitat for migration, with predicted foraging/reproduction suitable habitat in Southeast Asia region occurring on slope and in deep ocean waters. Suitable foraging habitat occurred primarily on slope and shelf break throughout most of Australia, with use of the continental shelf also occurring, predominanly in South West and Southern Australia. Depth of the water column (bathymetry) was consistently a top predictor of suitable habitat for most regions, however, dynamic environmental variables (sea surface temperature, surface height anomaly) influenced the probability of whale occurrence. Conclusions Our results indicate suitable habitat is related to dynamic, localised oceanic processes that may occur at fine temporal scales or seasonally. An increase in the sample size of tagged whales is required to move towards developing more dynamic distribution models at seasonal and monthly temporal scales. Our validation metrics also indicated areas where further data collection is needed to improve model accuracy. This is of particular importance for pygmy blue whale management, since threats (e.g., shipping, underwater noise and artificial structures) from the offshore energy and shipping industries will persist or may increase with the onset of an offshore renewable energy sector in Australia.

Abstract Introduction Many dialysis centres prescribe a uniform dialysate sodium (DialNa) concentration, but as there is no consensus on the choice of a universal DialNa, we wished to determine dialysate sodium balance comparing DialNa of 140 and

Background: Inadequate nutrition is common for both sarcopenia and frailty. We investigated whether hemodialysis patients with sarcopenia and frailty have reduced dietary intakes. Methods: Dietary intake, and physical activity were analyzed, along with body composition and relevant clinical data. Results: We studied 51 hemodialysis patients; 52.9% male, age 60 ± 15 years; 33.3% sarcopenic, and 72.5% frail. Dietary protein and calories were similar for sarcopenic and non-sarcopenic patients 0.68 (0.38–3.5) vs. 0.68 (0.18–2.9) g protein/kg/day and 19.2 (8.2–77.5) vs. 15.2 (6.2–38.5) kcal/kg/day. More sarcopenic patients had low physical activity (88.2% vs. 58.8%, X 2 4.6, p = .03). Frail and non-frail patients had similar intakes 0.67 (0.28–3.5) versus 0.83 (0.18–1.6) g protein/kg/day and 15.5 (8.1–77.5) vs. 18.8 (6.2–45.4) kcal/kg/day. Sarcopenia was associated with age [Odds ratio (OR) 1.09, 95% confidence interval (CI) [1.02, 1.18], p = .017], body mass index [OR 0.84, 95% CI [0.71, 0.99], p = .042] and lack of exercise [OR 7.62, 95% CI [1.16, 50.29], p = .035]. Frailty was associated with female gender [OR 17.79, 95% CI [2.09, 151.59], p = .008], age [OR 1.13, 95% CI [1.04, 1.22], p = .006], and dialysis vintage [OR 1.55, 95% CI [1.06, 2.26], p = .024]. Conclusion: Hemodialysis patients with sarcopenia and frailty did not have lower dietary protein and calorie intake. Frailty was associated with age and sarcopenia with a sedentary lifestyle.

Abstract Background Volume assessment, dry weight titration, and blood pressure control in pregnant kidney failure patients are often challenging, with physiological fluid accumulation in the trunk and lower limbs and an increased risk of preeclampsia. We used segmental bioimpedance in the volume management of our kidney failure patient on haemodialysis. Case presentation We report a case of a female patient on maintenance haemodiafiltration with no residual kidney function for whom we used segmental bioimpedance to guide dry weight adjustment. At different gestational periods, we targeted a different extracellular to total body water ratio according to body segments. This allowed us to support her high-risk pregnancy, identify her as probably developing preeclampsia and trigger a plan for closer monitoring and delivery during the third trimester when she had rapid weight gain. Conclusion Segmental bioimpedance is a practical, simple, and non-invasive test that can be performed at the dialysis unit and is useful as an adjunct decision-making tool in the management of pregnant dialysis patients.

BackgroundFrequent hemodialysis provided more than three times per week may lower mortality and improve health-related quality of life. Yet, the evidence is inconclusive. We evaluated the benefits and harms of frequent hemodialysis in people with kidney failure compared with standard hemodialysis.MethodsWe performed a systematic review of randomized controlled trials including adults on hemodialysis with highly sensitive searching in MEDLINE, Embase, CENTRAL, and Google Scholar on 3 January 2024. Data were pooled using random-effects meta-analysis. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. We adjudicated evidence certainty using GRADE.ResultsFrom 11,142 unique citations, only seven studies involving 518 participants proved eligible. The effects of frequent hemodialysis on physical and mental health were imprecise due to few data. Frequent hemodialysis probably had uncertain effect on death from all cause compared with standard hemodialysis (relative risk 0.79, 95% confidence interval 0.33-1.91, low certainty evidence). Data were not reported for death from cardiovascular causes, major cardiovascular events, fatigue or vascular access.ConclusionThe evidentiary basis for frequent hemodialysis is incomplete due to clinical trials with few or no events reported for mortality and cardiovascular outcome measures and few participants in which patient-reported outcomes including health-related quality of life and symptoms were reported.

Chronic kidney disease poses a growing global health concern, as an increasing number of patients progress to end-stage kidney disease requiring kidney replacement therapy, presenting various challenges including shortage of care givers and cost-related issues. In this narrative essay, we explore innovative strategies based on in-depth literature analysis that may help healthcare systems face these challenges, with a focus on digital health technologies (DHTs), to enhance removal and ensure better control of broader spectrum of uremic toxins, to optimize resources, improve care and outcomes, and empower patients. Therefore, alternative strategies, such as self-care dialysis, home-based dialysis with the support of teledialysis, need to be developed. Managing ESKD requires an improvement in patient management, emphasizing patient education, caregiver knowledge, and robust digital support systems. The solution involves leveraging DHTs to automate HD, implement automated algorithm-driven controlled HD, remotely monitor patients, provide health education, and enable caregivers with data-driven decision-making. These technologies, including artificial intelligence, aim to enhance care quality, reduce practice variations, and improve treatment outcomes whilst supporting personalized kidney replacement therapy. This narrative essay offers an update on currently available digital health technologies used in the management of HD patients and envisions future technologies that, through digital solutions, potentially empower patients and will more effectively support their HD treatments.

As the use of coastal and offshore environments expands, there is a need to better understand the exposure of marine megafauna to anthropogenic activities that potentially threaten their populations. Individual satellite telemetry studies are often hampered by small sample sizes, providing limited information on spatiotemporal distributions of migratory animals and their relationships to anthropogenic threats. We addressed this issue by synthesising satellite tracking data from 484 individuals of three taxonomic groups and six species; three marine turtle, two whale and one shark. The spatial overlap between taxa distributions and multiple anthropogenic activities was assessed as a proxy for the cumulative exposure of these taxa to anthropogenic threats (coastal modification, vessel strike, underwater noise, oil spill, bycatch, entanglement, and artificial light) across an area totalling 2,205,740 km2 off north-western Australia. Core exposure areas (top 50% of the distribution) encompassed ecologically important sites for all taxa, such as the Ningaloo and Pilbara regions, migratory routes for whales and sharks in offshore waters beyond Ningaloo Reef, and marine turtle nesting beaches at Barrow Island and Cape Lambert. Although areas of high exposure represented

Abstract Background Haemodialysis (HD) patients are at increased risk of frailty, sarcopenia and protein energy wasting, all associated with increased mortality. Most of the dialysis day is taken up with travelling to and from dialysis centres and dialysis treatment. The International Society of Nutrition and Metabolism (ISNM) recommend that meals or supplements should be part of standard clinical practice when patients attending for dialysis. Results We surveyed adult UK centres to determine the provision of food to dialysis patients in the United Kingdom (UK). A hot meal was provided by six (8.7%) of the 69 UK adult units, although 16 (23.2%) main centres would potentially provide meals to a restricted number of malnourished patients. Forty-seven (68.1%) centres provided sandwiches, although this was restricted in eight main centres, and 26.2% of units did not provide sandwiches to patients in their satellite dialysis centres. Biscuits were the only nutrition routinely offered in 15 (21.7%) of the main dialysis units, 41.3% of satellite units. Meals were more likely to be offered in Northern Ireland and Scotland compared to England, and 38% of the main dialysis units in England, and 58% of their satellite centres did not routinely offer patients a sandwich compared to none or one centre in Wales, Scotland and Northern Ireland. Conclusions Despite an increasing older, more frail dialysis population in the UK, food provision for dialysis patients has reduced, particularly in England, with 50% of dialysis units now only offering biscuits to their satellite dialysis patients.

Abstract Background Introducing a de-novo home haemodialysis (HHD) program often raises safety concerns as errors could potentially lead to serious adverse events. Despite the complexity of performing haemodialysis at home without the supervision of healthcare staff, HHD has a good safety record. We aim to pre-emptively identify and reduce the risks to our new HHD program by risk assessment and using failure mode and effects analysis (FMEA) to identify potential defects in the design and planning of HHD. Methods We performed a general risk assessment of failure during transitioning from in-centre to HHD with a failure mode and effects analysis focused on the highest areas of failure. We collaborated with key team members from a well-established HHD program and one HHD patient. Risk assessment was conducted separately and then through video conference meetings for joint deliberation. We listed all key processes, sub-processes, step and then identified failure mode by scoring based on risk priority numbers. Solutions were then designed to eliminate and mitigate risk. Results Transitioning to HHD was found to have the highest risk of failure with 3 main processes and 34 steps. We identified a total of 59 areas with potential failures. The median and mean risk priority number (RPN) scores from failure mode effect analysis were 5 and 38, with the highest RPN related to vascular access at 256. As many failure modes with high RPN scores were related to vascular access, we focussed on FMEA by identifying the risk mitigation strategies and possible solutions in all 9 areas in access-related medical emergencies in a bundled- approach. We discussed, the risk reduction areas of setting up HHD and how to address incidents that occurred and those not preventable. Conclusions We developed a safety framework for a de-novo HHD program by performing FMEA in high-risk areas. The involvement of two teams with different clinical experience for HHD allowed us to successfully pre-emptively identify risks and develop solutions.

Cardiovascular disease (CVD) is a major burden in dialysis-dependent chronic kidney disease (CKD5D) patients. Several factors contribute to this vulnerability including traditional risk factors such as age, gender, life style and comorbidities, and non-traditional ones as part of dialysis-induced systemic stress. In this context, it appears of utmost importance to bring a closer attention to CVD monitoring in caring for CKD5D patients to ensure early and appropriate intervention for improving their outcomes. Interestingly, new home-used, self-operated, connected medical devices offer convenient and new tools for monitoring in a fully automated and ambulatory mode CKD5D patients during the interdialytic period. Sensoring devices are installed with WiFi or Bluetooth. Some devices are also available in a cellular version such as the Withings Remote Patient Monitoring (RPM) solution. These devices analyze the data and upload the results to Withings HDS (Hybrid data security) platform servers. Data visualization can be viewed by the patient using the Withings Health Mate application on a smartphone, or with a web interface. Health Care Professionals (HCP) can also visualize patient data via the Withings web-based RPM interface. In this narrative essay, we analyze the clinical potential of pervasive wearable sensors for monitoring ambulatory dialysis patients and provide an assessment of such toolkit digital medical health devices currently available on the market. These devices offer a fully automated, unobtrusive and remote monitoring of main vital functions in ambulatory subjects. These unique features provide a multidimensional assessment of ambulatory CKD5D patients covering most physiologic functionalities, detecting unexpected disorders (i.e., volume overload, arrhythmias, sleep disorders) and allowing physicians to judge patient’s response to treatment and recommendations. In the future, the wider availability of such pervasive health sensing and digital technology to monitor patients at an affordable cost price will improve the personalized management of CKD5D patients, so potentially resulting in improvements in patient quality of life and survival.

Abstract Background More than a third of the 65,000 people living with kidney failure in the UK attend a dialysis unit 2–5 times a week to have their blood cleaned for 3–5 h. In haemodialysis (HD), toxins are removed by diffusion, which can be enhanced using a high-flux dialyser. This can be augmented with convection, as occurs in haemodiafiltration (HDF), and improved outcomes have been reported in people who are able to achieve high volumes of convection. This study compares the clinical- and cost-effectiveness of high-volume HDF compared with high-flux HD in the treatment of kidney failure. Methods This is a UK-based, multi-centre, non-blinded randomised controlled trial. Adult patients already receiving HD or HDF will be randomised 1:1 to high-volume HDF (aiming for 21+ L of substitution fluid adjusted for body surface area) or high-flux HD. Exclusion criteria include lack of capacity to consent, life expectancy less than 3 months, on HD/HDF for less than 4 weeks, planned living kidney donor transplant or home dialysis scheduled within 3 months, prior intolerance of HDF and not suitable for high-volume HDF for other clinical reasons. The primary outcome is a composite of non-cancer mortality or hospital admission with a cardiovascular event or infection during follow-up (minimum 32 months, maximum 91 months) determined from routine data. Secondary outcomes include all-cause mortality, cardiovascular- and infection-related morbidity and mortality, health-related quality of life, cost-effectiveness and environmental impact. Baseline data will be collected by research personnel on-site. Follow-up data will be collected by linkage to routine healthcare databases — Hospital Episode Statistics, Civil Registration, Public Health England and the UK Renal Registry (UKRR) in England, and equivalent databases in Scotland and Wales, as necessary — and centrally administered patient-completed questionnaires. In addition, research personnel on-site will monitor for adverse events and collect data on adherence to the protocol (monthly during recruitment and quarterly during follow-up). Discussion This study will provide evidence of the effectiveness and cost-effectiveness of HD as compared to HDF for adults with kidney failure in-centre HD or HDF. It will inform management for this patient group in the UK and internationally. Trial registration ISRCTN10997319 . Registered on 10 October 2017

BackgroundDepression is common amongst patients receiving haemodialysis (HD). Assessment and intervention when faced with language and cultural barriers is challenging. To support clinician decisions, we conducted a cross-sectional study to assess the use of culturally adapted and translated versions of commonly-used depression screening questionnaires with South Asian patients receiving HD in England.MethodsPatients completed adapted versions of the Patient Health Questionnaire (PHQ-9), the Centre for Epidemiological Studies Depression Scale Revised (CESD-R), and the Beck Depression Inventory II (BDI-II). All questionnaires were available in Gujarati, Punjabi, Urdu, and Bengali. A comparative sample of white-Europeans completed the questionnaires in English. The research was based across 9 National Health Service (NHS) Trusts in England. Structural validity of translated questionnaires was assessed using confirmatory factor analysis. Diagnostic accuracy was explored in a subgroup of South Asians against ICD-10 categories using the Clinical Interview Schedule Revised (CIS-R) with receiver operating curve (ROC) analysis.Results229 South Asian and 120 white-European HD patients participated. A single latent depression factor largely accounted for the correlations between items of the PHQ-9, CESD-R and BDI-II. Issues with measurement equivalence implied that scores on the translations may not be comparable with the English language versions. Against CIS-R based ICD-10 diagnosis of depression, sensitivity was modest across scales (50-66.7%). Specificity was higher (81.3-93.8%). Alternative screening cut-offs did not improve positive predictive values.ConclusionsCulturally adapted translations of depression screening questionnaires are useful to explore symptom endorsement amongst South Asian patients. However, data indicate that standard cut-off scores may not be appropriate to classify symptom severity. Use of the CIS-R algorithms for optimal case identification requires further exploration in this setting. Strategies to encourage recruitment of under-represented groups in renal research are also warranted, especially for in-depth discussions related to psychological care needs.

Abstract Intradialytic hypotension (IDH) and peridialytic blood pressure (BP) trends are associated with morbidity and mortality in haemodialysis (HD) patients. We aimed to characterise the respective influence of volume status and small solutes variation on peridialytic systolic BP (SBP) trends during HD. We retrospectively analysed the relative peridialytic SBP decrease in 647 prevalent outpatients attending for their mid-week session with corresponding pre- and post-HD bioelectrical impedance analysis. Mean SBP decreased by 10.5 ± 23.6 mmHg. Factors positively associated with the relative decrease in SBP were: serum sodium (Na) decrease, body mass index, serum albumin, dialysis vintage, ultrafiltration rate and urea Kt/V (p

Pygmy blue whales in the South-east Indian Ocean migrate from the southern coast of Australia to Indonesia, with a significant part of their migration route passing through areas subject to oil and gas production. This study aimed at improving our understanding of the spatial extent of the distribution, migration and foraging areas, to better inform impact assessment of anthropogenic activities in these regions. Using a combination of passive acoustic monitoring of the NW Australian coast (46 instruments from 2006 to 2019) and satellite telemetry data (22 tag deployments from 2009 to 2021) we quantified the pygmy blue whale distribution and important areas during their northern and southern migration. We show extensive use of slope habitat off Western Australia and only minimal use of shelf habitat, compared to southern Australia where use of the continental shelf and shelf break predominates. In addition, movement behaviour estimated by a state-space model on satellite tag data showed that in general pygmy blue whales off Western Australia were mostly engaged in migration, interspersed with relatively short periods (median = 28 h, range = 2 – 1080 h) of low move persistence (slow movement with high turning angles), which is indicative of foraging. Using the spatial overlap of time and number of whales in area analysis of the satellite tracking data (top 50% of grid cells) with foraging movement behaviour, we quantified the spatial extent of pygmy blue whale high use areas for foraging and migration. We compared these areas to the previously described areas of importance to foraging and migrating whales (Biologically Important Areas; BIAs). In some cases these had good agreement with the most important areas we calculated from our data, but others had only low (

Background: Both frailty and cachexia increase mortality in haemodialysis (HD) patients. The clinical frailty score (CFS) is a seven-point scale and less complex than other cachexia and frailty assessments. We wished to determine the characteristics of frail HD patients using the CFS. Methods: Single centre cross-sectional study of HD patients completing physical activity questionnaires with bioimpedance measurements of body composition and hand grip strength (HGS). Results: We studied 172 HD patients. The CFS classified 54 (31.4%) as frail, who were older (70.4±12.2 vs 56.2 ± 16.1 years, p < 0.001), greater modified Charlson co-morbidity (3 (2–3) versus 1.5 (0–3), p < 0.001), and body fat (33 (25.4–40.2) versus 26.2 (15.8–34) %, p < 0.01), but lower total energy expenditure (1720 (1574–1818) versus 1870 (1670–2194) kcal/day, p < 0.01), lean muscle mass index (9.1 (7.7–10.1) versus 9.9 (8.9–10.8) kg/m2), and HGS (15.3 (10.3–21.9) versus 23.6 (16.7–34.4) kg), both p < 0.001. On multivariable logistic analysis, frailty was independently associated with lower active energy expenditure (odds ratio (OR) 0.98, 95% confidence limits (CL) 0.98–0.99, p = 0.001), diabetes (OR 5.09, CL 1.06–16.66) and HGS (OR 0.92, CL 0.86–0.98). Discussion: Frail HD patients reported less active energy expenditure, associated with reduced muscle mass and strength. Frail patients were more likely to have greater co-morbidity, particularly diabetes. Whether physical activity programmes can improve frailty remains to be determined.

Background Increasing number of peritoneal dialysis (PD) patients are reported to have increased left ventricular hypertrophy (LVH), a major risk factor for cardiovascular mortality. We wished to determine which factors were most associated with changes in left ventricular mass index (LVMI). Methods We reviewed patient and treatment factors in prevalent PD patients with repeat echocardiograms 18 to 24 months apart, with corresponding bioimpedance measurements of extracellular water (ECW) and serum N-terminal pro-brain natriuretic peptide (NT-proBNP). Results We studied 60 patients (34 males, 35 with diabetes) who were treated with PD for a median of 14 months (2.5–26.3 months). All but one had LVH; on repeat echocardiography, there was no overall change in LVMI (106 [84–127] g/m2 vs. 108 [91–122] g/m2) despite a loss of residual renal function. Left ventricular mass increased in 34 (56.7%), and the percent change in LVMI was associated with percent change in NT-proBNP (r = 0.51, p = 0.017) and ECW/height (r = 0.32, p = 0.029), but not with ECW/total body water or changes in systolic or mean arterial pressure, urine output, 24-hour PD ultrafiltration, or net sodium balance. Only ECW/height remained independently associated with the percent change in LVMI in a multivariable model (odds ratio, 1.25; 95% confidence interval, 1.08–1.36; p = 0.007). Conclusion In this observational longitudinal report, a reduction in ECW/height was associated with regression of LVMI, whereas an increased ECW/height was associated with increased LVMI. As there was no corresponding association with systolic or mean arterial pressure, then volume expansion would appear to be a more significant factor in determining LVH than blood pressure.

Abstract Background Due to a critical shortage of available kidney grafts, most patients with Stage 5 Chronic Kidney Disease (CKD5) require bridging dialysis support. It remains unclear whether treatment by different dialysis modalities changes the selection and/or preparation of a potential transplant candidate. Therefore, we assessed whether the likelihood of receiving kidney transplant (both living or deceased kidney donors) differs between haemodialysis (HD) and online haemodiafiltration (HDF) in patients with CKD5D. Methods Individual participant data from four randomised controlled trials comparing online HDF with HD were used. Information on kidney transplant was obtained during follow-up. The likelihood of receiving a kidney transplant was compared between HD and HDF, and evaluated across different subgroups: age, sex, diabetes, history of cardiovascular disease, albumin, dialysis vintage, fistula, and level of convection volume standardized to body surface area. Hazard ratios (HRs), with corresponding 95% confidence intervals (95% CI), comparing the effect of online HDF versus HD on the likelihood of receiving a kidney transplant, were estimated using Cox proportional hazards models with a random effect for study. Results After a median follow-up of 2.5 years (Q1 to Q3: 1.9–3.0), 331 of the 1620 (20.4%) patients with CKD5D received a kidney transplant. This concerned 22% (n = 179) of patients who were treated with online HDF compared with 19% (n = 152) of patients who were treated with HD. No differences in the likelihood of undergoing a kidney transplant were found between the two dialysis modalities in both the crude analyse (HR: 1.07, 95% CI: 0.86–1.33) and adjusted analysis for age, sex, diabetes, cardiovascular history, albumin, and creatinine (HR: 1.15, 95%-CI: 0.92–1.44). There was no evidence for a differential effect across subgroups based on patient- and disease-characteristics nor in different categories of convection volumes. Conclusions Treatment with HD and HDF does not affect the selection and/or preparation of CKD5D patients for kidney transplant given that the likelihood of receiving a kidney transplant does not differ between the dialysis modalities. These finding persisted across a variety of subgroups differing in patient and disease characteristics and is not affected by the level of convection volume delivered during HDF treatment sessions.

Abstract Background Quality of life for haemodialysis (HD) patients may be affected by symptoms during dialysis treatments, and patient groups have highlighted the need to improve post-dialysis fatigue and dialysis-related symptoms. As changes in extracellular water (ECW) may lead to cramps and other symptoms, we wished to determine whether there was an association between ECW and intra-dialytic symptoms. Methods We reviewed the hospital records of HD patients who completed a self-reported intra-dialytic symptom questionnaire, using a visual analogue scale, who had contemporaneous pre- and postdialysis bioimpedance ECW measurements adjusted to height (aECW). Results We studied dialysis sessions of 506 patients, 314 (62.1%) male, 226 (44.7%) diabetic, mean age 64.6 ± 15.7 years, weight 69.9 ± 17.4 kg, and duration of dialysis treatment 26 (9.6–60.1) months. We divided patients into three groups according to pre-dialysis aECW, and total dialysis symptom scores were greater for those in the lower tertile (25 (10–41) vs middle 18 (8.5–34) vs upper 20 (7–31), p < 0.05). Only feeling cold, dizziness, and low blood pressure were statistically different between the three pre-dialysis aECW groups, and there was no difference in post-dialysis recovery times. We analysed the effect of the fall in aECW pre-to post-dialysis. Patients in the group with the greatest fall in aECW did not report more intra-dialytic symptoms or longer recovery times. Conclusion We found that patients starting dialysis with lower relative ECW were more likely to report intra-dialytic symptoms than those with greater amounts of fluid to remove, and most commonly reported symptoms were associated with intra-vascular volume depletion.

Abstract Community‐based conservation has been identified as a solution to biodiversity loss, climate change and the reduction of rural poverty. The heterogeneity in social and economic inequalities often acts as a barrier to community engagement in resource management and further inhibits the distributional equity of social and ecological outcomes. This study presents a participatory impact assessment (PIA) framework that evaluated the outcomes of a cross‐sector community‐led conservation initiative. Community members involved in the programme identified activities and outcomes for the conservation cooperative (CC), ranking the influence of the former on the latter as well as their daily life through multiple focus group discussions (FGDs). Participants were asked to rank the impact of activities on outcomes and the scale of the outcome which was totalled to identify the most impactful programme activities and outcomes during the project period. Community members reported improved income, health, education and the creation of a locally led natural resource management system. Members also reported improved crab harvest rates and reduced mangrove deforestation. Environmental outcomes identified by community members through the PIA were verified through a secondary spatial analysis and mud crab independent fisheries monitoring. The results support the hypothesis that environmental non‐governmental organizations (NGOs) need to consider a multi‐dimensional view of human well‐being, and that cross‐sector integrated interventions may be effective at improving multiple outcomes. Future steps should focus on spatial replication of the CC programme which will provide further insights by testing for differences in outcomes between villages, how those are impacted by pre‐existing social and ecological systems and comparing outcomes between control sites that did not receive interventions. A free Plain Language Summary can be found within the Supporting Information of this article.

Background Hypercalcemia is an uncommon finding in people living with HIV (PLHIV). Causes of hypercalcemia in PLHIV have not been well documented. As such, we studied the causes of hypercalcemia in PLHIV. Methods We conducted a retrospective review of PLHIV who had corrected serum calcium of ≥10.5 mg/dL between 2010 and 2019. Demographic data, associated diseases, and treatment details were collected. Corrected serum calcium levels were compared among the causes of hypercalcemia. Results A total of 70 of 2168 (3.2%) PLHIV had hypercalcemia. Forty-nine (70.0%) were male with a mean age of 47.7 ± 4.7 years. Only two (2.9%) had symptoms of hypercalcemia. Fifty-four patients had identifiable causes of hypercalcemia; 21 infections (30.0%), 17 solid organ malignancies (24.3%), 14 hematologic malignancies (20.0%), and two other specific causes (2.9%). Mean corrected serum calcium concentrations of PLHIV who had solid organ malignancy, hematologic malignancy, infection, and unknown causes were 12.8 ± 2.1, 11.4 ± 1.0, 11.2 ± 0.6, and 10.8 ± 0.2 mg/dL, respectively. Corrected serum calcium levels were significantly greater in patients who had solid organ malignancy comparing to those with other causes of hypercalcemia (p

Elderly patients with chronic kidney disease treated by haemodialysis are at increased risk of malnutrition and cachexia, becoming frail, with associated greater mortality. The physical performance test (PPT), using nine tasks to assess multiple domains of physical function is robust and reproducible, but time consuming, whereas the clinical frailty score (CFS) is more rapid. We compared the results from independent blinded observers in 22 haemodialysis patients, 16 (72.7%) male, mean age 65 ± 12.5 years. The PPT and CFS scores were highly correlated (r = −0.88, p < .001), with a high level of agreement (kappa score 0.91) for classifying patients as frail. Both scores were strongly associated with serum creatinine (PPT r=0.76, CFS r=−0.86, p < .001), hand grip strength (PPT r = 0.68, p = .001 CFS r = 0.64, p = .002), lean body mass index (PPT r = 0.50, p = .02, CFS r = −0.46, p = .038). We found that the CFS performed favourably compared to the PPT for haemodialysis patients in identifying and screening patients for frailty.

Renal cachexia is an important consideration in the person-centred care that is needed in end-stage renal disease (ESRD). However, given that clinical guidelines relating to renal cachexia are largely absent, this is an unmet care need. To inform guidelines and future renal service planning, there is an urgency to understand individuals' experiences of renal cachexia and the interrelated experiences of the carers in their lives. We report here the protocol for an interpretative phenomenological study which will explore this lived experience. A purposive sampling strategy will recruit individuals living with ESRD who have cachexia and their carers. A maximum of 30 participants (15 per group) dependent on saturation will be recruited across two nephrology directorates, within two healthcare trusts in the United Kingdom. Individuals with renal cachexia undergoing haemodialysis will be recruited via clinical gatekeepers and their carers will subsequently be invited to participate in the study. Participants will be offered the opportunity to have a face-to-face, virtual or telephone interview. Interviews will be audio-recorded, transcribed verbatim and analysed using interpretative phenomenological analysis. NVivo, will be used for data management. Ethical approval for this study was granted by the Office for Research Ethics Committees Northern Ireland (REC Reference: 22/NI/0107). Scientific evidence tends to focus on measurable psychological, social and quality of life outcomes but there is limited research providing in-depth meaning and understanding of the views of individuals with renal disease who are experiencing renal cachexia. This information is urgently needed to better prepare healthcare providers and in turn support individuals with ESRD and their carers. This study will help healthcare providers understand what challenges individuals with ESRD, and their carers face in relation to cachexia and aims to inform future clinical practice guidelines and develop supportive interventions which recognise and respond to the needs of this population.

Introduction: Peri-procedural i.v. fluid administration is important for the prevention of contrast-induced acute kidney injury (CI-AKI). However, standardized fluid management protocols may not be suitable for all patients. We therefore wished to determine whether an individualized fluid administration protocol guided by measuring extracellular water (ECW) using bioimpedance analysis (BIA) would be safe and would reduce the incidence CI-AKI compared to a standardized fluid administration prescription. Methods: In this pilot, randomized, parallel-group, single-blind, controlled trial, we compared the effect of BIA-guided isotonic bicarbonate administration according to the ratio of ECW to total body water (ECW/TBW) to our standard isotonic bicarbonate protocol in regard to the safety and efficacy of preventing CI-AKI in chronic kidney disease patients undergoing elective cardiac angiography. Our primary outcome was the incidence of CI-AKI, which was defined as a ≥0.3 mg/dl or 150% increase in serum creatinine concentration within 48 to 72 hours after cardiac angiography. Results: We studied 61 patients, 30 in the bioimpedance group and 31 in the control group. Age was similar (72.5 ± 7 vs. 71.4 ± 7.9 years), as were body mass index (25.5 vs. 25.8 kg/m2) and baseline serum creatinine (1.3 ± 0.3 vs. 1.4 ± 0.4 mg/dl). The peri-procedural fluid volume administered was significantly greater in the BIA-guided hydration group (899.0 ± 252.7 ml vs. 594.4 ± 125.9 ml, P < .01). The incidence of CI-AKI was 3.3% in BIA-guided hydration group and 6.5% in the control group (relative risk = 0.52, 95% confidence interval = 0.05−5.40, P = 1.00). Adverse events reported were comparable between groups (6.7% vs. 6.5%, P = 1.00). Conclusions: The overall incidence of CI-AKI after cardiac angiography in our patients with mild-to-moderate renal insufficiency was lower than anticipated. Isotonic bicarbonate administration guided by bioimpedance measurements was safe, and probably led to a lower incidence of CI-AKI, although this not reach statistical significance.

Introduction: Online postdilution hemodiafiltration (HDF) is associated with a lower all-cause and cardiovascular mortality than hemodialysis (HD). This may depend on a superior peridialytic (pre- and postdialysis, and the difference between these 2 parameters) hemodynamic profile. Methods: In this retrospective cohort analysis of individual participant data (IPD) from 3 randomized controlled trials (RCTs) (n = 2011), the effect of HDF and HD on 2-year peridialytic blood pressure (BP) patterns was assessed. Long-term peridialytic systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP), as well as the deltas (post- minus predialytic) were assessed in the total group of patients. Thereafter, these variables were compared between patients on HD and HDF, and in the latter group between quartiles of convection volume. Results: Mean pre- and postdialysis SBP, DBP, and MAP declined significantly during follow-up (predialytic: SBP −2.16 mm Hg, DBP −2.88 mm Hg, MAP −2.64 mm Hg), PP increased (predialytic 0.96 mm Hg). Peridialytic deltas remained unaltered. Differences between the 2 modalities, or between quartiles of convection volume were not observed. BP changes were independent of various baseline characteristics, including the decline in body weight over time. Conclusion: We speculate that the combination of a decreasing SBP and an increasing PP may be the clinical sequelae of a worsening cardiovascular system. Because especially HDF with a high convection volume has been associated with a beneficial effect on survival, our study does not support the view that superior peridialytic BP control contributes to this effect. Keywords: blood pressure, hemodiafiltration, hemodialysis, individual participant data, peridialytic

Abstract Background Haemodialysis (HD) patients may suffer symptoms during dialysis and take time to recover post HD. We wished to determine whether patients with symptomatic intra-dialytic hypotension (IDH), requiring nursing interventions, or an asymptomatic fall in systolic blood pressure (SBP) reported more symptoms during dialysis. Methods Six hundred three HD patients completed self-reported intra-dialytic symptom questionnaires and recovery using a visual analogue scale, which were compared with their dialysis session records. Results Twenty-nine (4.8%) of patients suffered symptomatic IDH, and 187 (31.0%) had a fall in SBP of > 20 mmHg. Symptomatic patients had greater total symptom scores (30 (23–44) vs 23 (10–38), p < 0.05, versus asymptomatic patients, with increased low blood pressure, dizziness, cramps, palpitations and feeling cold reported (all p < 0.05). Patients with a SBP fall of > 20 mmHg had greater total scores compared with those with a SBP increase of > 10 mmHg (26 (13–38) vs 17 (7–34), p < 0.05), with more dizziness, cramps, backache, shortness of breath and headache reported (all p < 0.05). Although ultrafiltration rates were similar, HD weight loss was greater for patients with a SBP fall of > 20 mmHg (2.5 ± 1.1 vs 2.0 ± 1.3%, p < 0.05). Patients with highest symptoms scores (highest vs lowest quartile) had longer recovery times (40.3 vs 7.6% > 4 h), p < 0.001. Multivariable analysis showed that patients reporting more intradialytic symptoms had higher psychological distress thermometer scores (odds ratio (OR) 1.34 (95% confidence limits 1.26–1.44)), systolic blood pressure < 100 mmHg (OR 2.53 (1.04–6.1)), whereas symptom scores were lower for male gender (OR 0.34 (0.22–0.51)), and with increasing age (OR 0.99 (0.97–0.99)). Conclusion Patients with both symptomatic and asymptomatic IDH, self-reported more symptoms during dialysis, and those patients reporting more symptoms had longer recovery times. We found that younger, female patients, those with greater psychological distress, and lower systolic blood pressure self-reported more intra-dialytic symptoms. More attention is required to prevent falls in intra-dialytic blood pressure to improve the patient experience of HD and shorten post-dialysis recovery times.

Background: Cardiac death is increased in peritoneal dialysis (PD) patients. Pulse wave velocity (PWV) is a measurement of arterial stiffness, and previous reports linked PWV to increased extracellular water (ECW). As cyclers and icodextrin are increasingly used, we wished to determine whether this association between PWV and ECW remains. Methods: We measured aortic PWV (aPWV) and bioimpedance (InBody, Seoul, South Korea) in consecutive PD patients attending for peritoneal membrane testing. Results: 189 patients were included, 62.4% male, mean age 63.1 ± 15.2 years, 45.3% diabetic, median dialysis duration 12.3 (6.5–25.1) months, 71.4% using cyclers, weight 73.0 ± 16.1 kg, systolic blood pressure 142 ± 21 mm Hg, aPWV 10.4 ± 5.1 m/s. aPWV was associated with pulse pressure (r = 0.26, p = 0.001), Davies comorbidity score (r = 0.18, p = 0.013), and N-terminal pro-brain-type natriuretic peptide (NTproBNP; r = 0.18, p = 0.011). Patients with aPWV ≥10 m/s were older (65.9 ± 13.6 vs. 60.1 ± 16.3 years, p < 0.01) with a higher ECW-to-total body water ratio (0.400 ± 0.012 vs. 0.396 ± 0.013, p < 0.05), but ECW/height was not different (8.52 ± 2.32 vs. 8.75 ± 1.78 L/m), as was NTproBNP (2,472 [788–5,422] vs. 1,234 [410–6,230] ng/L). On multivariable testing, aPWV was positively associated with β-blocker prescription (standardised β coefficient [Stβ] 0.3, 95% confidence limits [95% CL] 0.7–2.6, p = 0.001) and negatively with icodextrin prescription (Stβ 0.19, 95% CL –0.2 to –2.1, p = 0.04). Conclusions: Compared to previous studies, we did not find an independent association between aPWV and ECW and estimates of ECW excess, using the InBody bioimpedance device, suggesting that vascular stiffness in PD patients is more complex than simple ECW volume expansion in PD patients.

Abstract 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.

In this study, we aimed to develop a theoretical framework for a multimodal, integrative, exercise, anti-inflammatory and dietary counselling (MMIEAD) intervention for patients with renal cachexia with reference to how this addresses the underlying causal pathways for renal cachexia, the outcomes anticipated, and how these will be evaluated. We used a Theory of Change (ToC) approach to guide six steps. Step 1 included inputs from a workshop to obtain key stakeholder views on the potential development of a multimodal intervention for renal cachexia. Step 2 included the findings of a mixed-methods study with Health Care Practitioners (HCPs) caring for individuals with End Stage Kidney Disease (ESKD) and cachexia. Step 3 included the results from our systematic literature review on multimodal interventions for cachexia management. In step 4, we used the body of our research team’s cachexia research and wider relevant research to gather evidence on the specific components of the multimodal intervention with reference to how this addresses the underlying causal pathways for renal cachexia. In steps 5 and 6 we developed and refined the ToC map in consultation with the core research team and key stakeholders which illustrates how the intervention components of MMIEAD interact to achieve the intended long-term outcomes and anticipated impact. The results of this study provide a theoretical framework for the forthcoming MMIEAD intervention for those with renal cachexia and in subsequent phases will be used to determine whether this intervention is effective. To the best of our knowledge no other multimodal intervention trials for cachexia management have reported a ToC. Therefore, this research may provide a useful framework and contribute to the ongoing development of interventions for cachexia management.

Telemedicine has gained popularity during the recent COVID-19 pandemic. Regular and timely physician review is an essential component of care for the maintenance of hemodialysis patients. While it is widely acknowledged that telemedicine cannot fully replace the role of physical review in this group of patients with organ failure, it can perhaps reduce the reliance on physical review or serve as a filter and triage in determining which patient requires actual physical review. The use of technology in any healthcare setting should always align with existing clinical workflow and protocols. We discuss the safety and quality aspects of this new concept applied to the satellite dialysis unit.

Abstract Background Dialysis is a life-sustaining treatment, but many patients suffer symptoms during dialysis and take time to recover. Previous reports have linked recovery time to intra-dialytic hypotension and rapid solute clearances, whereas others have reported an association with psychological factors. As such, we wished to investigate which factors were important in determining symptom self-reporting and delayed recovery times. Methods We recorded self-reported patient intra-dialytic symptoms, recovery times along with sessional dialysis prescriptions, blood pressure and urea clearance, and distress thermometer scores to assess psychological factors. Findings Six hundred twenty-three dialysis patients were studied; 621 treated by haemodiafiltration, 60.8% male, mean age 64.5 ± 16.2 years, and 46.1% diabetic. Almost half (49.6%) reported recovery within 1 h. On multivariate analysis, patient self-reported symptom scores were associated with longer post-dialysis recovery times (odds ratio (OR) 1.61, 95% confidence limits (CL) 1.33–1.95), higher distress thermometer scores (OR 1.3 CL (1.3–1.39), but lower hand grip strength (OR 0.85 CL (0.93–0.94), all p

BackgroundDialysis patients have an increased risk of mortality. Recently treatment with haemodiafiltration (HDF) has been reported to reduce mortality, particularly cardiovascular mortality, compared to standard high-flux haemodialysis (HD). However, why HDF may offer a survival advantage remains to be determined. So, we conducted a pilot study to explore differences in middle-molecules, inflammation and markers of vascular disease in patients treated by HD and HDF.MethodsObservational cross-sectional study measuring serum β2-microglobulin (β2M), Advanced Glycosylation End Products (AGEs) by skin autofluorescence (SAF), oxidative stress with ischaemia modified albumin ratio (IMAR) and peripheral vascular disease assessment using Ankle-Brachial Index (ABI), and arterial stiffness using Cardio-Ankle Vascular Index (CAVI).ResultsWe studied 196 patients, mean age 69.1 ± 12.4 years, 172 (87.8%) treated by HD and 24 (12.2%) by HDF. Age, body mass index, co-morbidity and dialysis vintage were not different between HD and HDF groups. Middle molecules; β2M (31±9.9 vs 31.2±10 ug/mL) and SAF (2.99±0.72 vs 3.0±0.84 AU), ABI (1.06±0.05 vs 1.07±0.10) and CAVI (9.34±1.55 vs 9.35±1.23) were not different, but IMAR was higher in the HD patients (38.4±14.8 vs 31.3 ± 17.4, P = 0.035).ConclusionsIn this pilot observational study, we found patients treated by HDF had lower oxidative stress as measured by IMAR, with no differences in middle molecules. Lower oxidative stress would be expected to have diverse protective effects on the cardiovascular system Although we found no differences in ABI and CAVI, future studies are required to determine whether reduced oxidative stress translates into clinically relevant differences over time.

BACKGROUND:On-line hemodiafiltration (HDF) clears more azotemic toxins compared to high-flux hemodialysis (HD). The response to vaccination is impaired in dialysis patients. We wished to determine whether the immune responses to influenza vaccine in dialysis patients treated by HDF were stronger than those treated by HD. MATERIALS AND METHODS:We conducted a prospective cohort study in chronic dialysis patients during the 2016 and 2017 influenza seasons. All participants received a single standard dose of trivalent influenza vaccine, and we studied the elicited humoral immune response by hemagglutination inhibition test, and cell-mediated immune response by enumeration of lymphocyte cellular markers and proliferation assays. RESULTS:We immunized 60 end-stage renal disease (ESRD) patients: 42 (70%) treated with HD and 18 patients (30%) with HDF. The median (interquartile range) age was 65.0 (55.0-74.5) years. All patients developed seroprotection to at least one influenza vaccine strain at one month post-vaccination, and did not differ between groups. By logistic regression, age was the only factor independently associated with seroconversion to all vaccine strains (odds ratio 0.89, 95% confidence interval 0.80-0.98; p = 0.022). Seroprotection to all vaccine strains was sustained for longer in patients treated with HDF, and the results remained the same after age adjustment. For cellular immune response, patients who seroconverted to all vaccine strains had higher CD38+ T cell subpopulations pre-vaccination. Patients treated by HDF had higher lymphocyte proliferation to circulating influenza A strains. CONCLUSIONS:Seroconversion to all influenza vaccine strains was associated with age. Patients treated with HDF demonstrated seroprotection was sustained for longer compared to those treated by HD and greater lymphocyte proliferation to circulating influenza A strains. These encouraging results for HDF require confirmation in a larger dialysis population. TRIAL REGISTRATION:ClinicalTrial.gov, NCT04122222.

Abstract Background Surveys using traditional measures of nutritional status indicate that muscle wasting is common among persons with end-stage kidney disease (ESKD). Up to 75% of adults undergoing maintenance dialysis show some evidence of muscle wasting. ESKD is associated with an increase in inflammatory cytokines and can result in cachexia, with the loss of muscle and fat stores. At present, only limited data are available on the classification of wasting experienced by persons with ESKD. Individuals with ESKD often exhibit symptoms of anorexia, loss of lean muscle mass and altered energy expenditure. These symptoms are consistent with the syndrome of cachexia observed in other chronic diseases, such as cancer, heart failure, and acquired immune deficiency syndrome. While definitions of cachexia have been developed for some diseases, such as cardiac failure and cancer, no specific cachexia definition has been established for chronic kidney disease. The importance of developing a definition of cachexia in a population with ESKD is underscored by the negative impact that symptoms of cachexia have on quality of life and the association of cachexia with a substantially increased risk of premature mortality. The aim of this study is to determine the clinical phenotype of cachexia specific to individuals with ESKD. Methods A longitudinal study which will recruit adult patients with ESKD receiving haemodialysis attending a Regional Nephrology Unit within the United Kingdom. Patients will be followed 2 monthly over 12 months and measurements of weight; lean muscle mass (bioelectrical impedance, mid upper arm muscle circumference and tricep skin fold thickness); muscle strength (hand held dynamometer), fatigue, anorexia and quality of life collected. We will determine if they experience (and to what degree) the known characteristics associated with cachexia. Discussion Cachexia is a debilitating condition associated with an extremely poor outcome. Definitions of cachexia in chronic illnesses are required to reflect specific nuances associated with each disease. These discrete cachexia definitions help with the precision of research and the subsequent clinical interventions to improve outcomes for patients suffering from cachexia. The absence of a definition for cachexia in an ESKD population makes it particularly difficult to study the incidence of cachexia or potential treatments, as there are no standardised inclusion criteria for patients with ESKD who have cachexia. Outcomes from this study will provide much needed data to inform development and testing of potential treatment modalities, aimed at enhancing current clinical practice, policy and education.

More than three million patients are treated for kidney failure world-wide. Haemodialysis, the most commonly used treatment, requires large amounts of water and generates mountains of non-recyclable plastic waste. To improve the environmental footprint, dialysis treatments need to develop absorbents to regenerate the waste dialysate. Whereas conventional dialysis clears water-soluble toxins, it is not so effective in clearing protein-bound uraemic toxins (PBUTs), such as indoxyl sulfate (IS). Thus, developing absorption devices to remove both water-soluble toxins and PBUTs would be advantageous. Vapour induced phase separation (VIPS) has been used in this work to produce polycaprolactone/chitosan (PCL/CS) composite symmetric porous monoliths with extra porous carbon additives to increase creatinine and albumin-bound IS absorption. Moreover, these easy-to-fabricate porous monoliths can be formed into the required geometry. The PCL/CS porous monoliths absorbed 436 μg/g of albumin-bound IS and 2865 μg/g of creatinine in a single-pass perfusion model within 1 h. This porous PCL/CS monolith could potentially be used to absorb uraemic toxins, including PBUTs, and thus allow the regeneration of waste dialysate and the development of a new generation of environmentally sustainable dialysis treatments, including wearable devices.

Abstract Background Preserved residual kidney function (RKF) and normal fluid status are associated with better patient outcomes in incident haemodialysis patients. The objective of this trial is to determine whether using bioimpedance technology in prescribing the optimal post-dialysis weight can reduce the rate of decline of RKF and potentially improve patient outcomes. Methods/Design 516 pateints commencing haemodialysis, aged >18 with RKF of > 3 ml/min/1.73 m2 or a urine volume >500 ml per day or per the shorter inter-dialytic period will be consented and enrolled into a pragmatic, open-label, randomized controlled trial. The intervention is incorporation of bioimpedance spectroscopy (BI) determination of normally hydrated weight to set a post-dialysis target weight that limits volume depletion, compared to current standard practice. Clinicians and participants will be blinded to BI measures in the control group and a standardized record capturing management of fluid status will be used in all participants. Primary outcome is preservation of residual kidney function assessed as time to anuria (≤100 ml/day or ≤200 ml urine volume in the short inter-dialytic period). A sample size of 516 was based upon a cumulative incidence of 30% anuria in the control group and 20% in the treatment group and 11% competing risks (death, transplantation) over 10 months, with up to 2 years follow-up. Secondary outcomes include rate of decline in small solute clearance, significant adverse events, hospitalization, loss of vascular access, cardiovascular events and interventions, dialysis efficacy and safety, dialysis-related symptoms and quality of life. Economic evaluation will be carried out to determine the cost-effectiveness of the intervention. Analyses will be adjusted for patient characteristics and dialysis unit practice patterns relevant to fluid management. Discussion This trial will establish the added value of undertaking BI measures to support clinical management of fluid status and establish the relationship between fluid status and preservation of residual kidney function in incident haemodialysis patients. Trial registration ISCCTN Number: 11342007 , completed 26/04/2016; NIHR Portfolio number: CPMS31766; Sponsor: Keele University

Nephrotoxicity from drugs accounts for 18% to 27% of cases of acute kidney injury. Determining a genetic predisposition may potentially be important in minimizing risk. The aims of this study are as follows: to determine whether a genetic predisposition exists for the development of drug-induced kidney disease (DIKD), using genome-wide association and whole-genome sequencing studies; to describe the frequency, course, risk factors, resolution and outcomes of DIKD cases; to investigate the role of ethnic/racial variability in the genetics of DIKD; and to explore the use of different tools establishing causality of DIKD. Methods: A total of 800 patients will be enrolled worldwide and blood samples for DNA collected. Data on the patient risk factors, vital signs, laboratory parameters, drug exposure, and DIKD course will be recorded. A panel of nephrologists will adjudicate all cases. Genome-wide association studies will be conducted using population controls matched on biogeographic ancestry to determine whether there is a genetic predisposition to DIKD. The primary endpoint is the identification of specific drug-related polymorphisms associated with DIKD. Secondary endpoints include the following: frequency of DIKD by causal drug and drug combinations; DIKD genetic variability; exploration of causality assessment tools; risk factor identification; description of the course of DIKD, including mortality and dialysis dependency at hospital discharge and 28 and 90 days post-event. Results: Data are currently being analyzed. Results are pending. Discussion: The Genetic Contribution to Drug Induced Renal Injury (DIRECT) study will be the first observational cohort study to investigate the genetic determinants of DIKD. If the trial is positive, its findings will potentially translate into safer patient outcomes, by genotypic individualization of therapy and minimization of harm.

Current practice basing dialysis dose on urea distribution volume (V) has been questioned. We explored the impact on survival of scaling dialysis dose (Kt) to parameters reflective of metabolic activity. In a multicentre prospective cohort study of 1500 patients on thrice-weekly haemodialysis, body surface area (BSA) and resting energy expenditure (REE) were estimated using validated equations and physical activity by the Recent Physical Activity Questionnaire. Total energy expenditure (TEE) was estimated from REE and physical activity data. Kt was calculated from delivered (single-pool Kt/V)*Watson V. Kt/BSA, Kt/REE and Kt/TEE were then calculated at baseline and 6 monthly during follow-up for 2 years. In adjusted Cox models Kt/TEE, Kt/BSA, Kt/REE, in that order, had lower hazard ratios for death than single-pool Kt/V. On the basis of adjusted survival differences, putative minimum target doses were estimated for Kt/BSA as 27119 ml/m2 and Kt/TEE as 25.79 ml/kcal. We identified spKt/V values equivalent to these estimated targets, ranging from 1.4 to 1.8 in patient groups based on gender, body size and physical activity. For sedentary patients, the minimum target dose was 1.4 for large males, 1.5 for small males and 1.7 for women. For active patients the target was 1.8 irrespective of gender and body-weight. Patients achieving these individualised minimum targets had greater adjusted two-year survival compared to those achieving conventional minimum targets. Metabolic activity related parameters, such as Kt/TEE and Kt/BSA, may have a clinically important role in scaling haemodialysis dose. Using such parameters or their spKt/V equivalents to adjust minimum target doses based on gender, body size and habitual physical activity may have a positive impact on survival.

Little is known on long-term outcomes in kidney transplantation. This study evaluated changes and predictors of generic and transplantation-specific health-related quality of life (HQoL) over six years in N=102 kidney transplant survivors using the Short-form Health Survey-36 and the Transplant Effects questionnaire. Mixed models analysis was used to determine long-term outcomes. Emotional HQoL improved over time: Mental Component score, Mental Health, Energy (Ps=.000). Physical HQoL deteriorated: Physical Component Score (P=.001), Pain (P=.002). LRD transplant recipients had greater decline in physical functioning (P=.003) and PCS (P=.000) compared to cadaver recipients. Worry about the transplant (P=.036) and feelings of responsibility (P=.008) increased significantly over time. Worry about the transplant and perceived ability to work predicted 12.7% and 31.1% in variance in MCS and PCS, respectively. Efforts should be made to maintain HQoL and emotional outcomes with ongoing monitoring and support programs throughout the course of posttransplant care.

One mechanism by which bacteria survive environmental stress is through the formation of bacterial persisters, a sub-population of genetically identical quiescent cells that exhibit multidrug tolerance and are highly enriched in bacterial toxins. Recently, the Escherichia coli gene mqsR (b3022) was identified as the gene most highly upregulated in persisters. Here, we report multiple individual and complex three-dimensional structures of MqsR and its antitoxin MqsA (B3021), which reveal that MqsR:MqsA form a novel toxin:antitoxin (TA) pair. MqsR adopts an alpha/beta fold that is homologous with the RelE/YoeB family of bacterial ribonuclease toxins. MqsA is an elongated dimer that neutralizes MqsR toxicity. As expected for a TA pair, MqsA binds its own promoter. Unexpectedly, it also binds the promoters of genes important for E. coli physiology (e.g., mcbR, spy). Unlike canonical antitoxins, MqsA is also structured throughout its entire sequence, binds zinc and coordinates DNA via its C- and not N-terminal domain. These studies reveal that TA systems, especially the antitoxins, are significantly more diverse than previously recognized and provide new insights into the role of toxins in maintaining the persister state.