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Background: This study evaluated parenting stress, anxiety, and depression symptoms and their associated factors in parents of children with chronic kidney disease (CKD). Methods: This cross-sectional study compared parents of patients with CKD (0–18 years) with a matched control group of parents of healthy children. Both groups completed the Parenting Stress Index – Short Form, the Hospital Anxiety and Depression Scale, and a sociodemographic questionnaire. Results: The study group consisted of 45 parents (median age 39; 32 mothers) of CKD patients (median age 8; 36% female). Nearly 75% of children had CKD stages 2, 3, or 4, and 44.5% had congenital anomaly of the kidney and urinary tract. Five children (11%) were on dialysis, and 4 (9%) had a functioning kidney graft. Compared with parents of healthy children, more stress and anxiety symptoms were reported. Since the CKD diagnosis, 47% of parents perceived a deterioration of their own health, and 40% reduced work on a structural basis. Higher levels of stress, anxiety, and depression symptoms were associated with a more negative perception of own health, and more child medical comorbidities and school absence. Conclusions: This study showed higher levels of parenting stress and anxiety symptoms in parents of children with CKD compared with parents of healthy children. This was associated with a less positive perception of their own health, especially if the child had more medical comorbidities or more absence from school. Psychosocial interventions to reduce the parental burden should be integrated in the standard care of pediatric nephrology departments. [ABSTRACT FROM AUTHOR]

To promote improved trial design in upcoming randomized clinical trials in childhood chronic kidney disease (CKD), insight in the within- and inter-patient variability of uremic toxins with its nutritional, treatment- and patient-related confounding factors is of utmost importance. In this study, the within- and inter-patient variability of a selection of uremic toxins in a longitudinal cohort of children diagnosed with CKD was assessed, using the intraclass correlation coefficient (ICC) and the within-patient coefficient of variation (CV). Subsequently, the contribution of anthropometry, estimated glomerular filtration rate (eGFR), dietary fiber and protein, and use of (prophylactic) antibiotics to uremic toxin variability was evaluated. Based on 403 observations from 62 children (median seven visits per patient; 9.4 ± 5.3 years; 68% males; eGFR 38.5 [23.1; 64.0] mL/min/1.73 m2) collected over a maximum of 2 years, we found that the within-patient variability is high for especially protein-bound uremic toxins (PBUTs) (ICC < 0.7; within-patient CV 37–67%). Moreover, eGFR was identified as a predominant contributor to the within- and inter-patient variability for the majority of solutes, while the impact of the child's anthropometry, fiber and protein intake, and antibiotics on the variability of uremic toxin concentrations was limited. Based on these findings, we would recommend future intervention studies that attempt to decrease uremic toxin levels to select a (non-dialysis) CKD study population with a narrow eGFR range. As the expected effect of the selected intervention should exceed the inter-patient variability of the selected uremic toxins, a narrow eGFR range might aid in improving the trial design. [ABSTRACT FROM AUTHOR]

The population‐attributable fraction (PAF) is commonly interpreted as the proportion of events that can be ascribed to a certain exposure in a certain population. Its estimation is sensitive to common forms of time‐dependent bias in the face of a time‐dependent exposure. Predominant estimation approaches based on multistate modeling fail to fully eliminate such bias and, as a result, do not permit a causal interpretation, even in the absence of confounding. While recently proposed multistate modeling approaches can successfully eliminate residual time‐dependent bias, and moreover succeed to adjust for time‐dependent confounding by means of inverse probability of censoring weighting, inadequate application, and misinterpretation prevails in the medical literature. In this paper, we therefore revisit recent work on previously proposed PAF estimands and estimators in settings with time‐dependent exposures and competing events and extend this work in several ways. First, we critically revisit the interpretation and applied terminology of these estimands. Second, we further formalize the assumptions under which a causally interpretable PAF estimand can be identified and provide analogous weighting‐based representations of the identifying functionals of other proposed estimands. This representation aims to enhance the applied statistician's understanding of different sources of bias that may arise when the aim is to obtain a valid estimate of a causally interpretable PAF. To illustrate and compare these representations, we present a real‐life application to observational data from the Ghent University Hospital ICUs to estimate the fraction of ICU deaths attributable to hospital‐acquired infections. [ABSTRACT FROM AUTHOR]

Prevention of clotting in hemodialysis (HD) is a concern, but tools to monitor anticoagulation strategies as well as data on bleeding and its impact on quality of life (QoL) are scant. In this prospective longitudinal observational study, bleeding tendency in 70 HD patients was scored with ISTH-BAT and HAS-BLED at week 0, 4, and 8. Patient's limbs were visually scored for bruises and hematomas, and Quality of Life (QoL) was assessed using EQ5D-3L and Visual Analogue Scale (VAS) questionnaires. At week 0, the used hemodialyzer was scanned in a micro-CT scanner to quantify the number of patent fibers. Bleeding scores were 0 [0; 1] and 3 [2; 4] for ISTH-BAT and HAS-BLED, and visual scoring showed 2 [0; 4] bruises/hematomas. QoL was 0.85 [0.77; 1.00] for EQ5D and 70 [60; 80] for VAS. Fiber patency was 81 [70; 90]%, but was not associated with anticoagulation dose (p = 0.103). Patients in the highest tertile of anticoagulation dose had a worse VAS score (p = 0.027), and patients identified as having bleeding tendency by ISTH also had a worse VAS score (p = 0.010). This supports our postulate that in maintenance HD patients the current personal anticoagulation dose regimens may be too high, leading to more mainly minor bleeding that may negatively impact health related quality of life. [ABSTRACT FROM AUTHOR]

Adolescents and young adults (AYAs) benefit from healthcare transition (HCT) programs. Despite the well-established literature reviewing HCT, a considerable heterogeneity exists on the involved healthcare professionals. This review aims to explore systematic reviews on the practices and recommendations on which disciplines of professionals should be involved in HCT. An umbrella review was performed using the MEDLINE, EMBASE, and Web of Science databases. To be eligible, systematic reviews had to report on the composition and/or the rationale of members of a transition team. Seventeen reviews were included in this systematic review. A healthcare professional that coordinates HCT was identified as a key caregiver in all reviews. Other reported members of a HCT team were nurses (75% of the reviews), social workers (44%), and peers/mentors (35%). The reported key responsibilities of a HCT team were to (i) manage communication, (ii) ensure continuity of care, and (iii) maintain contact with community services. Conclusions: A team responsible for HCT should be active on the organizational, medical, and social levels. Key members of a HCT team vary little between diseases and included a coordinator, social worker, and nurse. A coordinating physician could facilitate transition in complex conditions. At all times, the condition and needs of the AYA should determine who should be involved as caregiver. What is Known: • The psychosocial needs of adolescents and young adults during healthcare transition are largely similar between chronic diseases. What is New: • Coordinators, nurses and social workers were the most involved, independent of the condition. • A liaison team should be active on organizational-, medical- and social-levels. [ABSTRACT FROM AUTHOR]

Background and Objectives: Defining the optimal moment to start renal replacement therapy (RRT) in acute kidney injury (AKI) remains challenging. Multiple randomized controlled trials (RCTs) addressed this question whilst using absolute criteria such as pH or serum potassium. However, there is a need for identification of the most optimal cut-offs of these criteria. We conducted a causal analysis on routinely collected data (RCD) to compare the impact of different pre-specified dynamic treatment regimes (DTRs) for RRT initiation based on time-updated levels of potassium, pH, and urinary output on 30-day ICU mortality.Design, Setting, Participants, and Measurements: Patients in the ICU of Ghent University Hospital were included at the time they met KDIGO-AKI-stage ≥ 2. We applied inverse-probability-of-censoring-weighted Aalen-Johansen estimators to evaluate 30-day survival under 81 DTRs prescribing RRT initiation under different thresholds of potassium, pH, or persisting oliguria.Results: Out of 13,403 eligible patients (60.8 ± 16.8 years, SOFA 7.0 ± 4.1), 5622 (63.4 ± 15.3 years, SOFA 8.2 ± 4.2) met KDIGO-AKI-stage ≥ 2. The DTR that delayed RRT until potassium ≥ 7 mmol/l, persisting oliguria for 24-36 h, and/or pH < 7.0 (non-oliguric) or < 7.2 (oliguric) despite maximal conservative treatment resulted in a reduced 30-day ICU mortality (from 12.7% [95% CI 11.9-13.6%] under current standard of care to 10.5% [95% CI 9.5-11.7%]; risk difference 2.2% [95% CI 1.3-3.8%]) with no increase in patients starting RRT (from 471 [95% CI 430-511] to 475 [95% CI 342-572]). The fivefold cross-validation benchmark for the optimal DTR resulted in 30-day ICU mortality of 10.7%.Conclusions: Our causal analysis of RCD to compare RRT initiation at different thresholds of refractory low pH, high potassium, and persisting oliguria identified a DTR that resulted in a decrease in 30-day ICU mortality without increase in number of RRTs. Our results suggest that the current criteria to start RRT as implemented in most RCTs may be suboptimal. However, as our analysis is hypothesis generating, this optimal DTR should ideally be validated in a multicentric RCT. [ABSTRACT FROM AUTHOR]

The optimal moment to start renal replacement therapy in a patient with acute kidney injury (AKI) remains a challenging problem in intensive care nephrology. Multiple randomized controlled trials have tried to answer this question, but these contrast only a limited number of treatment initiation strategies. In view of this, we use routinely collected observational data from the Ghent University Hospital intensive care units (ICUs) to investigate different prespecified timing strategies for renal replacement therapy initiation based on time‐updated levels of serum potassium, pH, and fluid balance in critically ill patients with AKI with the aim to minimize 30‐day ICU mortality. For this purpose, we apply statistical techniques for evaluating the impact of specific dynamic treatment regimes in the presence of ICU discharge as a competing event. We discuss two approaches, a nonparametric one — using an inverse probability weighted Aalen‐Johansen estimator — and a semiparametric one — using dynamic‐regime marginal structural models. Furthermore, we suggest an easy to implement cross‐validation technique to assess the out‐of‐sample performance of the optimal dynamic treatment regime. Our work illustrates the potential of data‐driven medical decision support based on routinely collected observational data. [ABSTRACT FROM AUTHOR]

Introduction: Hyperlactatemia is a regular condition in the intensive care unit, which is often associated with adverse outcomes. Control of the triggering condition is the most effective treatment of hyperlactatemia, but since this is mostly not readily possible, extracorporeal renal replacement therapy (RRT) is often tried as a last resort. The present study aims to evaluate the factors that may contribute to the decision whether to start RRT or not and the potential impact of the start of RRT on the outcome in patients with severe lactic acidosis (SLA) (lactate ≥5 mmol/L). Materials and Methods: We conducted a retrospective single-center cohort analysis over a 3-year period including all patients with a lactate level ≥5 mmol/L. Patients were considered as treated with RRT because of SLA if RRT was started within 24 h after reaching a lactate level ≥5 mmol/L. Results: Overall, 90-day mortality in patients with SLA was 34.5%. Of the 1,203 patients who matched inclusion/exclusion criteria, 11% (n = 133) were dialyzed within 24 h. The propensity to receive RRT was related to the lactate level and to the SOFA renal and cardio score. The most frequently used modality was continuous RRT. Patients who were started on RRT versus those who did not have 2.3 higher odds of mortality, even after adjustment for the propensity to start RRT. Conclusions: Our analysis confirms the high mortality rate of patients with SLA. It adds that odds for mortality is even higher in patients who were started on RRT versus not. We suggest keeping an open mind to the factors that may influence the decision to start dialysis and bear in mind that without being a bridge to correction of the underlying condition, dialysis is unlikely to affect the outcome. [ABSTRACT FROM AUTHOR]

The combination of "Big Data" and Artificial Intelligence (AI) is frequently promoted as having the potential to deliver valuable health benefits when applied to medical decision-making. However, the responsible adoption of AI-based clinical decision support systems faces several challenges at both the individual and societal level. One of the features that has given rise to particular concern is the issue of explainability, since, if the way an algorithm arrived at a particular output is not known (or knowable) to a physician, this may lead to multiple challenges, including an inability to evaluate the merits of the output. This "opacity" problem has led to questions about whether physicians are justified in relying on the algorithmic output, with some scholars insisting on the centrality of explainability, while others see no reason to require of AI that which is not required of physicians. We consider that there is merit in both views but find that greater nuance is necessary in order to elucidate the underlying function of explainability in clinical practice and, therefore, its relevance in the context of AI for clinical use. In this paper, we explore explainability by examining what it requires in clinical medicine and draw a distinction between the function of explainability for the current patient versus the future patient. This distinction has implications for what explainability requires in the short and long term. We highlight the role of transparency in explainability, and identify semantic transparency as fundamental to the issue of explainability itself. We argue that, in day-to-day clinical practice, accuracy is sufficient as an "epistemic warrant" for clinical decision-making, and that the most compelling reason for requiring explainability in the sense of scientific or causal explanation is the potential for improving future care by building a more robust model of the world. We identify the goal of clinical decision-making as being to deliver the best possible outcome as often as possible, and find--that accuracy is sufficient justification for intervention for today's patient, as long as efforts to uncover scientific explanations continue to improve healthcare for future patients. [ABSTRACT FROM AUTHOR]

Free plasma concentrations of protein-bound uremic toxins (PBUTs) may be influenced by serum albumin and hemoglobin. The potential association of serum albumin and hemoglobin with free levels of p-cresyl sulfate (pCS) and p-cresyl glucuronide (pCG) and their predictive value for cardiovascular morbidity and mortality were explored. A total of 523 non-dialysis chronic kidney disease (CKD) stages G1–G5 patients were prospectively followed for the occurrence of fatal or non-fatal cardiovascular events over a 5.5-year period. A negative correlation was found between albumin and between hemoglobin, and both total and free pCS and pCG. In multiple linear regression, PBUTs were negatively associated with eGFR (estimated glomerular filtration rate) and hemoglobin but not albumin. In multivariate Cox regression analysis, albumin was a predictor of outcome, independent of pCS and pCG, without interactions between albumin and pCS or pCG. The relation of low hemoglobin with adverse outcome was lost when albumin was entered into the model. Lower concentrations of pCS and pCG are associated with higher serum albumin and hemoglobin. This may indicate that there are two pathways in the blood that potentially contribute to attenuating the vasculotoxic effects of these PBUTs. The association of PBUTs with cardiovascular risk is not explained by albumin levels, which remains a strong and independent predictor for adverse outcome. [ABSTRACT FROM AUTHOR]

Background: There is increasing interest in incorporating clinical decision support (CDS) into electronic healthcare records (EHR). Successful implementation of CDS systems depends on acceptance of them by healthcare workers. We used a mix of quantitative and qualitative methods starting from Qsort methodology to explore expectations and perceptions of practicing physicians on the use of CDS incorporated in EHR.Methods: The study was performed in a large tertiary care academic hospital. We used a mixed approach with a Q-sort based classification of pre-defined reactions to clinical case vignettes combined with a thinking-aloud approach, taking into account COREQ recommendations The open source software of Ken-Q Analysis version 1.0.6. was used for the quantitative analysis, using principal components and a Varimax rotation. For the qualitative analysis, a thematic analysis based on the four main themes was performed based on the audiotapes and field notes.Results: Thirty physicians were interviewed (7 in training, 8 junior staff and 15 senior staff; 16 females). Nearly all respondents were strongly averse towards interruptive messages, especially when these also were obstructive. Obstructive interruption was considered to be acceptable only when it increases safety, is adjustable to user expertise level and/or allows deviations when the end-user explains why a deviation is desirable in the case at issue. Transparency was deemed an essential feature, which seems to boil down to providing sufficient clarification on the factors underlying the recommendations of the CDS, so that these can be compared against the physicians' existing knowledge, beliefs and convictions.Conclusion: Avoidance of disruptive workflows and transparency of the underlying decision processes are important points to consider when developing CDS systems incorporated in EHR. [ABSTRACT FROM AUTHOR]

Background: Fruit and vegetable intake is commonly discouraged in children with chronic kidney disease (CKD) to avoid hyperkalemia. However, direct evidence in support of this widespread practice is lacking. Furthermore, the resultant restricted fiber exposure may deprive CKD patients from potential health benefits associated with the latter. Therefore, we investigated associations between dietary potassium intake, fiber intake, and serum potassium levels in pediatric CKD. Methods: This study is a longitudinal analysis of a 2-year, prospective, multi-institutional study, following children with CKD at 3-month intervals. At each visit, dietary potassium and fiber intake were assessed, using 24-h recalls and 3-day food records. On the same occasion, serum potassium concentrations were determined. Associations between dietary potassium intake, dietary fiber intake, and serum potassium concentrations were determined using linear mixed models. Results: Fifty-two CKD patients (7 transplant recipients, none on dialysis) aged 9 [4;14] years with an estimated glomerular filtration rate (eGFR) of 49 [25;68] mL/min/1.73 m2 were included. For every g/day decrease in dietary potassium intake, the estimated mean daily fiber intake was 5.1 g lower (95% confidence interval (CI), 4.3–5.9 g/day; p < 0.001). Neither dietary potassium intake (p = 0.40) nor dietary fiber intake (p = 0.43) was associated with circulating potassium in a model adjusted for time point, eGFR, treatment with a renin–angiotensin–aldosterone system blocker, serum bicarbonate concentration, and body surface area. Conclusions: Dietary potassium and fiber intake are closely related but were not associated with circulating potassium levels in pediatric CKD. A higher-resolution version of the graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Background: Physical performance is an important determinant of quality of life in patients on haemodialysis. An association between physical performance and survival could further enhance the importance of physical performance. We aimed to assess the association between different measures of physical performance and survival in dialysis patients. Methods: 117 patients on haemodialysis were included from December 2016 and followed up to September 2020. Muscle strength (quadriceps, handgrip strength, and sit-to-stand), exercise capacity (six-minute walking test, 6MWT) and the risk of falls (Dialysis Fall Index, Tinetti, and Frailty and Injuries: Cooperative Studies of Intervention Techniques) were measured at the time of inclusion. Hospitalisation, morbidity (Davies Stoke index) and death were recorded. Data were analysed by least squares linear regression models and competing risks survival hazard models. Results: During the observation period (median 33, min 30 max 45 months), 45 patients died (= 38.5%), resulting in a mortality rate of 15% per year. Cardiovascular disease (42.9%) was the most common cause of death. All domains of physical performance were associated with mortality, with the highest hazards for an increased risk of falls (Hazard Ratio (HR) = 20.4, p = 0.003) and poor exercise capacity (HR = 7.4, p<0.001). A score lower than 298 meters (specificity = 0.583; sensitivity = 0.889) on the 6MWT was established as a haemodialysis-specific cut-off point for mortality risk. Each increase in 6MWT (m) corresponded with a 0.4% decrease in mortality risk (HR = 0.996, 95%CI [0.994; 0.998]). The 6MWT as also associated with comorbidity (F-value = 6.1, p = 0.015). Physical performance was not associated with hospitalisation. Conclusions: The 6MWT is associated with mortality in patients on haemodialysis and can be considered as a valid assessment tool to identify high-risk patients. [ABSTRACT FROM AUTHOR]

Research regarding the drivers of acceptance of clinical decision support systems (CDSS) by physicians is still rather limited. The literature that does exist, however, tends to focus on problems regarding the user-friendliness of CDSS. We have performed a thematic analysis of 24 interviews with physicians concerning specific clinical case vignettes, in order to explore their underlying opinions and attitudes regarding the introduction of CDSS in clinical practice, to allow a more in-depth analysis of factors underlying (non-)acceptance of CDSS. We identified three general themes from the results. First, 'the perceived role of the AI', including items referring to the tasks that may properly be assigned to the CDSS according to the respondents. Second, 'the perceived role of the physician', referring to the aspects of clinical practice that were seen as being fundamentally 'human' or non-automatable. Third, 'concerns regarding AI', including items referring to more general issues that were raised by the respondents regarding the introduction of CDSS in general and/or in clinical medicine in particular. Apart from the overall concerns expressed by the respondents regarding user-friendliness, we will explain how our results indicate that our respondents were primarily occupied by distinguishing between parts of their job that should be automated and aspects that should be kept in human hands. We refer to this distinction as 'the division of clinical labor.' This division is not based on knowledge regarding AI or medicine, but rather on which parts of a physician's job were seen by the respondents as being central to who they are as physicians and as human beings. Often the respondents' view that certain core parts of their job ought to be shielded from automation was closely linked to claims concerning the uniqueness of medicine as a domain. Finally, although almost all respondents claimed that they highly value their final responsibility, a closer investigation of this concept suggests that their view of 'final responsibility' was not that demanding after all. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) are important in pathophysiology of type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Dietary AGEs (dAGEs) contribute to the overall AGE pool in the body. Forty elderly T2DM patients with DKD were randomly allocated to a low-AGE (n = 20) or regular diabetic (n = 20) diet group. A three-day meal questionnaire was used to estimate average quantity of dAGEs. AGE accumulation was measured using skin autofluorescence and urine spectroscopy. sRAGE (soluble receptor AGE) was quantified using ELISA. After 8 weeks, the mean consumption of dAGEs was considerably reduced, both in the low-AGE diet (p = 0.004) and the control (p = 0.019) group. The expected urinary emission peak at 490 nm was shifted to 520 nm in some spectra. dAGEs did not correspond with urine AGE output. An AGE-limited diet for two months did not affect AGE content in skin and urine, or sRAGE concentration in the blood. The role of glycemia is likely to be greater than the impact of dAGE consumption. The unique observation of a fluorescence pattern at 520 nm warrants further examination, since it might point to genetic differences in AGE regulation, which could have clinical consequences, as AGE content depends on its formation and elimination. [ABSTRACT FROM AUTHOR]

Background: Children with chronic kidney disease (CKD) have a low quality of life (QoL). The PedsQL™ 4.0 Generic Core Scales are widely used to assess general QoL in children. The aim of this cross-sectional study was to translate the original version of the CKD-specific PedsQL™ 3.0 End Stage Renal Disease Module into a Dutch version and to evaluate its validity and reliability. Methods: The forward–backward translation method based on the guidelines from the original developer was used to produce the Dutch version of the PedsQL™ 3.0 ESRD Module. Fifty-eight CKD patients (aged 8–18 years) and their parents (n = 31) filled in both generic and disease-specific modules. The non-clinical control group consisted of the same number of healthy children (matched for gender and age) and their parents. Results: Cronbach's alpha coefficients (α's) for the PedsQL™ 3.0 ESRD Module demonstrated excellent reliability for the Total Scale scores. For all 7 subscales, α's were greater than 0.60, except for Perceived Physical Appearance. Overall, intercorrelations with the PedsQL™ 4.0 Generic Core Scales were in the medium to large range, supporting construct validity. Parent proxy reports showed lower generic QoL for all domains in CKD patients compared to healthy children. Child self-reports only demonstrated lower QoL on the domain School Functioning in children with CKD compared to healthy children. Conclusions: This study shows good validity and reliability for the Dutch version of the PedsQL™ 3.0 ESRD Module. However, testing with a larger study group is recommended in order to make final conclusions about the psychometric qualities of this measure. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Previous studies revealed the importance of biocompatibility, anticoagulation strategy, and dialysis mode and duration on fiber blocking at the end of a hemodialysis session. The present study was set up in ten hemodialysis patients to relate fiber patency to dialyzer extraction and removal of small and middle molecules. With only 1/4th of the regular anticoagulation dose, and using a Solacea 19H and FX800 CorDiax dialyzer, fiber patency was quantified using 3D micro-CT scanning for different dialysis durations (i.e. 60, 120 and 240 min). While Solacea showed enhanced fiber patency in all test sessions, fiber blocking in the FX800 CorDiax did not follow a linear process during dialysis, but was rather accelerated near the end of dialysis. Dialyzer extraction ratios were correlated with the percentages of open fibers. While the fiber blocking process affected extraction ratios (i.e. for phosphorus and myoglobin in the FX800 CorDiax), it had only minor impact on the removal of toxins up to at least 12 kDa. [ABSTRACT FROM AUTHOR]

Background: Immunocompromised patients are at increased risk of severe COVID-19 and impaired vaccine response. In this observational prospective study, we evaluated immunogenicity of the BNT162b2 mRNA vaccine in cohorts of primary or secondary immunocompromised patients. Methods: Five clinical groups of immunocompromised patients [primary immunodeficiency (PID) (n=57), people living with HIV (PLWH) (n=27), secondary immunocompromised patients with a broad variety of underlying rheumatologic (n=23) and homogeneous (multiple sclerosis) neurologic (n=53) conditions and chronic kidney disease (CKD) (n=39)] as well as a healthy control group (n=54) were included. Systemic humoral and cellular immune responses were evaluated by determination of anti-SARS-CoV-2 Spike antibodies using a TrimericS IgG assay (Diasorin) and through quantification of interferon gamma release in response to SARS-CoV-2 antigen with QuantiFERON SARS-CoV-2 assay (Qiagen), respectively. Responses were measured at pre-defined time-points after complete vaccination. Results: All healthy controls, PLWH and CKD-patients had detectable antibodies 10 to 14 days (T2) and 3 months (T3) after administration of the second vaccination. In contrast, only 94.5% of the PID, 50.0% of the rheumatologic and 48.0% of neurologic patients developed antibodies at T2 and only 89.1% of the PID, 52.4% of the rheumatologic and 50.0% of neurologic patients developed antibodies at T3. At T3 no significant differences in cellular response between the healthy control group and the PLWH and CKD groups were found, while proportions of reactive subjects were lower in PID and rheumatologic patients and higher in neurologic patients. Humoral and cellular immune responses significantly correlated in the healthy control, PID, PLWH groups for all 3 antigens. Conclusion: Patients with acquired or inherited immune disorders may show variable immune responses to vaccination with the BNT162b2 mRNA vaccine against SARS-CoV-2. Whether humoral, cellular or both immune responses are delayed depends on the patient group, therapy and individual risk factors. These data may guide the counselling of patients with immune disorders regarding vaccination of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The use of artificial intelligence (AI) in healthcare comes with opportunities but also numerous challenges. A specific challenge that remains underexplored is the lack of clear and distinct definitions of the concepts used in and/or produced by these algorithms, and how their real world meaning is translated into machine language and vice versa, how their output is understood by the end user. This "semantic" black box adds to the "mathematical" black box present in many AI systems in which the underlying "reasoning" process is often opaque. In this way, whereas it is often claimed that the use of AI in medical applications will deliver "objective" information, the true relevance or meaning to the end‐user is frequently obscured. This is highly problematic as AI devices are used not only for diagnostic and decision support by healthcare professionals, but also can be used to deliver information to patients, for example to create visual aids for use in shared decision‐making. This paper provides an examination of the range and extent of this problem and its implications, on the basis of cases from the field of intensive care nephrology. We explore how the problematic terminology used in human communication about the detection, diagnosis, treatment, and prognosis of concepts of intensive care nephrology becomes a much more complicated affair when deployed in the form of algorithmic automation, with implications extending throughout clinical care, affecting norms and practices long considered fundamental to good clinical care. [ABSTRACT FROM AUTHOR]

Purpose: Almost all CKD patients have a poor nutritional status, while elderly CKD patients are specifically frail and malnourished. Our aim is to conduct a systematic review of the up to date primary studies that look at methods of improving nutritional status in CKD patients in the elderly demographic. Methods: A focussed and sensitive search strategy was applied to the PUBMED database to identify relevant English language articles. Once articles were identified a detailed quality and bias assessment was performed. Two independent researchers (MZ and SM) then subsequently carried out detailed data extraction and analysis and this was subsequently verified by a third researcher (IN). Results: A total of 19 studies were included in our systematic review which included 7 non-randomised control trials and 15 randomised controlled trials. The outcomes that we considered to be most relevant for our subject title were: mortality data, SGA, albumin, total protein, isoleucine, leucine, prealbumin, transferrin, leptin, valine, TAG, HDL, LDL and total amino acids. Detailed bias analysis of the different studies was also conducted. Conclusion: This is the first systematic review of the literature, so far, on the subject, involving elderly CKD patients. The quality of trials is low, very heterogenic in patients, methods and outcomes. However, we found a positive effect of dietary interventions on the nutritional status of most patients studied, highlighted by improvement in serum albumin and SGA, the most measured outcomes. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) in children is a pro-inflammatory condition leading to a high morbidity and mortality. Accumulation of organic metabolic waste products, coined as uraemic toxins, parallels kidney function decline. Several of these uraemic toxins are protein-bound (PBUT) and gut-derived. Gut dysbiosis is a hallmark of CKD, resulting in a state of increased proteolytic fermentation that might be counteracted by dietary fibre. Data on fibre intake in children with CKD are lacking. We aimed to assess dietary fibre intake in a paediatric CKD cohort and define its relationship with PBUT concentrations. Methods: In this multi-centre, cross-sectional observational study, 61 non-dialysis CKD patients (9 ± 5 years) were included. Dietary fibre intake was assessed through the use of 24-h recalls or 3-day food records and coupled to total and free levels of 4 PBUTs (indoxyl sulfate (IxS), p-cresyl sulfate (pCS), p-cresyl glucuronide (pCG) and indole acetic acid (IAA). Results: In general, fibre intake was low, especially in advanced CKD: 10 ± 6 g/day/BSA in CKD 4–5 versus 14 ± 7 in CKD 1–3 (p = 0.017). Lower concentrations of both total (p = 0.036) and free (p = 0.036) pCG were observed in the group with highest fibre intake, independent of kidney function. Conclusions: Fibre intake in paediatric CKD is low and is even worse in advanced CKD stages. Current dietary fibre recommendations for healthy children are not being achieved. Dietary management of CKD is complex in which too restrictive diets carry the risk of nutritional deficiencies. The relation of fibre intake with PBUTs remains unclear and needs further investigation. Graphical abstract [ABSTRACT FROM AUTHOR]

Most reports on AKI claim to use KDIGO guidelines but fail to include the urinary output (UO) criterion in their definition of AKI. We postulated that ignoring UO alters the incidence of AKI, may delay diagnosis of AKI, and leads to underestimation of the association between AKI and ICU mortality. Using routinely collected data of adult patients admitted to an intensive care unit (ICU), we retrospectively classified patients according to whether and when they would be diagnosed with KDIGO AKI stage ≥ 2 based on baseline serum creatinine (Screa) and/or urinary output (UO) criterion. As outcomes, we assessed incidence of AKI and association with ICU mortality. In 13,403 ICU admissions (62.2% male, 60.8 ± 16.8 years, SOFA 7.0 ± 4.1), incidence of KDIGO AKI stage ≥ 2 was 13.2% when based only the SCrea criterion, 34.3% when based only the UO criterion, and 38.7% when based on both criteria. By ignoring the UO criterion, 66% of AKI cases were missed and 13% had a delayed diagnosis. The cause-specific hazard ratios of ICU mortality associated with KDIGO AKI stage ≥ 2 diagnosis based on only the SCrea criterion, only the UO criterion and based on both criteria were 2.11 (95% CI 1.85–2.42), 3.21 (2.79–3.69) and 2.85 (95% CI 2.43–3.34), respectively. Ignoring UO in the diagnosis of KDIGO AKI stage ≥ 2 decreases sensitivity, may lead to delayed diagnosis and results in underestimation of KDIGO AKI stage ≥ 2 associated mortality. [ABSTRACT FROM AUTHOR]

Background: The incidence of Acute Kidney Injury (AKI) and its human and economic cost is increasing steadily. One way to reduce the burden associated with AKI is to prevent the event altogether. An important step in prevention lies in AKI risk prediction. Due to the increasing number of available risk prediction models (RPMs) clinicians need to be able to rely on systematic reviews (SRs) to provide an objective assessment on which RPM can be used in a specific setting. Our aim was to assess the quality of SRs of RPMs in AKI. Methods: The protocol for this overview was registered in PROSPERO. MEDLINE and Embase were searched for SRs of RPMs of AKI in any setting from 2003 till August 2020. We used the ROBIS tool to assess the methodological quality of the retrieved SRs. Results: Eight SRs were retrieved. All studies were assessed as being at high risk for bias using the ROBIS tool. Eight reviews had a high risk of bias in study eligibility criteria (domain 1), five for study identification and selection (domain 2), seven for data collection and appraisal (domain 3) and seven for synthesis and findings (domain 4). Five reviews were scored at high risk of bias across all four domains. Risk of bias assessment with a formal risk of bias tool was only performed in five reviews. Primary studies were heterogeneous and used a wide range of AKI definitions. Only 19 unique RPM were externally validated, of which 11 had only 1 external validation report. Conclusion: The methodological quality of SRs of RPMs of AKI is inconsistent. Most SRs lack a formal risk of bias assessment. SRs ought to adhere to certain standard quality criteria so that clinicians can rely on them to select a RPM for use in an individual patient. Trial registration: PROSPERO registration number is CRD 42020204236, available at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=204236. [ABSTRACT FROM AUTHOR]

Over the last decades, the face of health care has changed dramatically, with big improvements in what is technically feasible. However, there are indicators that the current approach to evaluating evidence in health care is not holistic and hence in the long run, health care will not be sustainable. New conceptual and normative frameworks for the evaluation of health care need to be developed and investigated. The current paper presents a novel framework of justifiable health care and explores how the use of artificial intelligence and big data can contribute to achieving the goals of this framework. [ABSTRACT FROM AUTHOR]

Machine learning (ML) is gaining increased interest in clinical laboratory medicine, mainly triggered by the decreased cost of generating and storing data using laboratory automation and computational power, and the widespread accessibility of open source tools. Nevertheless, only a handful of ML-based products are currently commercially available for routine clinical laboratory practice. In this review, we start with an introduction to ML by providing an overview of the ML landscape, its general workflow, and the most commonly used algorithms for clinical laboratory applications. Furthermore, we aim to illustrate recent evolutions (2018 to mid-2020) of the techniques used in the clinical laboratory setting and discuss the associated challenges and opportunities. In the field of clinical chemistry, the reviewed applications of ML algorithms include quality review of lab results, automated urine sediment analysis, disease or outcome prediction from routine laboratory parameters, and interpretation of complex biochemical data. In the hematology subdiscipline, we discuss the concepts of automated blood film reporting and malaria diagnosis. At last, we handle a broad range of clinical microbiology applications, such as the reduction of diagnostic workload by laboratory automation, the detection and identification of clinically relevant microorganisms, and the detection of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

We present a patient with an angiosarcoma in an arteriovenous fistula and we reviewed current treatments for angiosarcomas. We extended the systematic review by Oskrochi et al. on this topic in 2015, using the same search query. We searched systematically OVID, EMBASE and PubMed from April 2015 until January 2020 with the aim to update the state of the art in managing this rare but serious condition. We retrieved 12 new case reports about 11 unique patients. Mean age was 61.5 ± 11 years. Six arteriovenous fistulas had failed spontaneously. Two fistulas were operatively closed post‐transplant. Nine patients (81.8%) were receiving ongoing immunosuppressive therapy. Pain and growing lesions, mass or swelling were the most frequent symptoms. Angiosarcoma mostly presents with a nonspecific clinical picture of pain, growing lesions and swelling of a previously normal arteriovenous fistula. Amputation of the limb was most frequently conducted as treatment in localized disease. Treatment of systemic disease included supportive care, chemotherapy, especially with paclitaxel and change of immunosuppressive regimen. Metastasized angiosarcoma has a very poor prognosis. Classical chemotherapy has rather low response rates. There is limited data supporting treatment of angiosarcomas with tyrosine kinase inhibitors or immunotherapy. Further comparative research is needed. [ABSTRACT FROM AUTHOR]

Objectives: In this study, the possibilities of Fourier-transformed infrared spectroscopy (FTIR) for analysis of urine sediments and for detection of bacteria causing urinary tract infections (UTIs) were investigated. Methods: Dried urine specimens of control subjects and patients presenting with various nephrological and urological conditions were analysed using mid-infrared spectroscopy (4,000–400 cm−1). Urine samples from patients with a UTI were inoculated on a blood agar plate. After drying of the pure bacterial colonies, FTIR was applied and compared with the results obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Chemometric data analysis was used to classify the different species. Results: Due to the typical molecular assignments of lipids, proteins, nucleic acids and carbohydrates, FTIR was able to identify bacteria and showed promising results in the detection of proteins, lipids, white and red blood cells, as well as in the identification of crystals. Principal component analysis (PCA) allowed to differentiate between Gram-negative and Gram-positive species and soft independent modelling of class analogy (SIMCA) revealed promising classification ratios between the different pathogens. Conclusions: FTIR can be considered as a supplementary method for urine sediment examination and for detection of pathogenic bacteria in UTI. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of bedside handover, as contrasted with traditional handovers, on length of hospital stay, unplanned readmission, hospital-acquired pressure ulcers (HAPUs), patient falls, unscheduled intravenous reinfusion and pain. Design: A multicentre matched-controlled longitudinal design. Method: Bedside handover was implemented at five intervention wards in a convenience sample of four hospitals (three surgical/medical wards and two wards for medical rehabilitation). Four control wards continued to use their traditional handover (two surgical-medical wards, one medical rehabilitation ward and one mixed surgicalmedical rehabilitation ward; one for each hospital). Patient records, including reports on individual patients in the electronic incident reporting systems, were consulted (N intervention = 509; N control = 265). The study was carried out between May 2016- February 2018 and data were collected between March 2018-June 2018. The data were analysed using generalized linear mixed-model analysis. Results: No significant differences in length of stay, unplanned readmission, HAPUs, unnecessary intravenous drips, pain or patients falls could be attributed to the use of bedside handovers, whether over time or between the intervention and the control groups. Conclusion: No long-term effects were found on patient safety arising from bedside handover. This lack of significance possibly indicates that: (a) caution is needed when generalizing the results of previous smaller-scale studies; and that (b) bedside handovers do not create hazardous situations for patients. Impact: Nurses traditionally perform change-of-shift handovers without the patient. However, the growth in attention paid to reducing adverse events and the demand for more participative and patient-centred approaches in health care both suggest that bedside handovers might be a logical intervention. This study could not confirm the positive results found in the international literature on the impact of bedside handovers on patient safety. Bedside handover should thus be considered as an equally safe, more patient-centred alternative to traditional handover models. [ABSTRACT FROM AUTHOR]

Background: Physical impairments are common in uraemia, as reflected by the high risk of falls of haemodialysis (HD) patients. Furthermore, these patients often suffer from malnutrition. Objective: Up to now, it is unknown which aspects of physical performance are predominantly driven by malnutrition in HD patients. As this answer could steer different interventions, the aim of this study was to evaluate the cross-sectional relationship between nutritional status, muscle strength, exercise capacity and the risk of falls. Methods: This study recruited HD patients between December 2016 and March 2018 from two hospital-based and five satellite dialysis units (registration number on clinicaltrial.gov: NCT03910426). The mini-nutritional assessment scale as well as objective measures of protein-energy wasting were obtained (total iron-binding capacity, total protein levels, and CRP). Physical assessment included muscle strength (quadriceps, handgrip force, and sit-to-stand test), exercise capacity (six-minute walking test) and the risk of falls (Tinetti, FICSIT, and dialysis fall index). Their interrelationship was analysed by ridge regression models. Results: Out of 113 HD patients (mean age 67 years ± 16.1, 57.5% male) 36.3% were malnourished according to the mini-nutritional assessment scale and a majority had impaired quadriceps force (86.7%), six-minute walking test (92%), and an increased risk of falls (73.5%). Total protein and CRP levels were identified as relevant nutritional factors in the association with physical performance. Nutritional parameters explained 9.2% of the variance in the risk of falls and 7.6% of the variance in exercise capacity. No conclusive association was found between nutritional status and muscle strength. Conclusion: Protein-energy wasting is a determinant of the risk of falls and exercise capacity in patients on HD. The association between malnutrition and muscle weakness remains inconclusive. [ABSTRACT FROM AUTHOR]

Background: Patient-centeredness, respect for patient autonomy, and shared decision-making have now made it to center stage in discussions on quality of care. Knowing what actually counts in care and how it should be accomplished from the patients' and nurses' perspective seems crucial. Aim: To explore how patients and their nurses perceive the importance and enactment of values in their healthcare. Research design: An observational, cross-sectional study using a self-developed questionnaire, consisting of 15 items related to seven values (e.g. uniqueness, autonomy, professionalism, compassion, responsiveness, partnership, and empowerment) as described in the taxonomy of Bastemeijer et al. Participants and research context: The survey was completed by 384 patients and 81 nurses. Participants were recruited on eight internal medicine wards of a 1000-bed university hospital in Belgium. Ethical considerations: This study was approved by the ethical committee of the Ghent University Hospital (B670201836799). Findings: (1) Patients and nurses prioritize values of care differently; (2) nurses report not being able to enact the values they prioritize in actual practice as much as one would like to; and (3) there is a gap in experienced delivery of a comprehensible explanation of all treatment options, a conversation based on equality, making shared decisions, and being non-judgmental between nurses and patients. Discussion: Our findings challenge nurses' overemphasis on professional compassion and uniqueness while arguing for increased attention on authentic shared decision-making and empowerment. The first step to a patient-centered culture truly involving patients in their healthcare is communication and information provision, rather than focusing on tangible and normative constructs. Conclusion: Our findings revealed differences in prioritization and actual enactment of values in care between patients and nurses. This was especially so for values related to communication, provision of complete unbiased information, and shared decision-making. Nurses should prioritize providing comprehensible information and using conversations based on equality to make decision together with patients. [ABSTRACT FROM AUTHOR]

Purpose: Malnutrition is prevalent in patients on dialysis and is associated with morbidity and mortality. Nutritional status can be assessed by a variety of biochemical and physical parameters or nutritional assessment scores. Most of these methods are expensive or cumbersome to use and are not suitable for routine repetitive follow-up in dialysis patients. The Mini Nutritional Assessment (MNA) has a short form screening set (MNA-SF), which would be suitable as a screening tool, but has not been validated yet in dialysis patients. We aimed to assess whether the MNA is an appropriate tool for identifying nutritional problems in dialysis patients. Method: MNA, routine biochemistry, physical parameters, comorbidities were assessed in cross-sectional multicentric cohorts of hemodialysis and peritoneal dialysis patients with a longitudinal follow up of 2 years for mortality. Results: In this cohort of 216 patients, mortality was 27.3% at a follow up of 750±350 days. The mean MNA-SF score was 9.9±1.8, with 30.1%, 59.3% and 10.6% of patients categorized as having normal nutritional status, at risk for malnutrition and malnourished, respectively. The screening score was associated with mortality (HR 0.86, 95% CI 0.75–0.98 per point). With normal nutrition as reference, adjusted mortality was 2.50 (95% CI 1.16–5.37) and 3.89 (95% CI 1.48–10.13) for patients at risk for malnutrition and with malnutrition, respectively. After recalibrating the MNA full score for the specificity of some of its domains for dialysis patients, the MNA-SF had a good sensitivity and specificity for not being well nourished (0.95 and 0.63 respectively) in the full score, and a high negative predictive value (0.91). Conclusion: The MNA-SF is independently associated with 2 year mortality in dialysis patients. It has a high negative predictive value for excluding being at risk or having malnutrition in the full score. Therefore, it can be advocated as a screening tool for nutritional status in dialysis patients. [ABSTRACT FROM AUTHOR]

Background: Impaired physical function due to muscle weakness and exercise intolerance reduces the ability to perform activities of daily living in patients with end-stage kidney disease, and by consequence, Health-Related Quality of Life (HRQoL). Furthermore, the risk of falls is an aggregate of physical function and, therefore, could be associated with HRQoL as well. The present study examined the associations between objective and subjective measures of physical function, risk of falls and HRQoL in haemodialysis patients.Methods: This cross-sectional multicentre study included patients on maintenance haemodialysis. Physical function (quadriceps force, handgrip force, Sit-to-Stand, and six-minute walking test), the risk of falls (Tinetti, FICSIT-4, and dialysis fall index) and HRQoL (PROMIS-29 and EQ-5D-3 L) were measured and analysed descriptively, by general linear models and logistic regression.Results: Of the 113 haemodialysis patients (mean age 67.5 ± 16.1, 57.5% male) enrolled, a majority had impaired quadriceps force (86.7%) and six-minute walking test (92%), and an increased risk of falls (73.5%). Whereas muscle strength and exercise capacity were associated with global HRQoL (R2 = 0.32) and the risk of falls, the risk of falls itself was related to psycho-social domains (R2 = 0.11) such as depression and social participation, rather than to the physical domains of HRQoL. Objective measures of physical function were not associated with subjective fatigue, nor with subjective appreciation of health status.Conclusions: More than muscle strength, lack of coordination and balance as witnessed by the risk of falls contribute to social isolation and HRQoL of haemodialysis patients. Mental fatigue was less common than expected, whereas, subjective and objective physical function were decreased. [ABSTRACT FROM AUTHOR]

Bedside handover is the delivery of the nurse-to-nurse handover at the patient's bedside. Although increasingly used in nursing, nurses report many barriers for delivering the bedside handover. Among these barriers is the possibility of breaching the patient's privacy. By referring to this concept, nurses add a legal and ethical dimension to the delivery of the bedside handover, making implementation of the method difficult or even impossible. In this discussion article, the concept of privacy during handovers is being discussed by use of observations, interviews with nurses, and interviews with patients. These findings are combined with international literature from a narrative review on the topic. We provide a practice-oriented answer in which two mutually exclusive possibilities are discussed. If bedside handover does pose problems concerning privacy, this situation is not unique in healthcare and measures can be taken during the bedside handover to safeguard the patient. If bedside handover does not pose problems concerning privacy, privacy is misused by nurses to hide professional uncertainties and/or a reluctance toward patient participation. Therefore, a possible breach of privacy—whether a justified argument or not—is not a reason for not delivering the bedside handover. [ABSTRACT FROM AUTHOR]

Dialyzer clearance of urea multiplied by dialysis time and normalized for urea distribution volume (Kt/Vurea or simply Kt/V) has been used as an index of dialysis adequacy since more than 30 years. This article reviews the flaws of Kt/V, starting with a lack of proof of concept in three randomized controlled hard outcome trials (RCTs), and continuing with a long list of conditions where the concept of Kt/V was shown to be flawed. This information leaves little room for any conclusion other than that Kt/V, as an indicator of dialysis adequacy, is obsolete. The dialysis patient might benefit more if, instead, the nephrology community concentrates in the future on pursuing the optimal dialysis dose that conforms with adequate quality of life and on factors that are likely to affect outcomes more than Kt/V. These include residual renal function, volume status, dialysis length, ultrafiltration rate, the number of intra-dialytic hypotensive episodes, interdialytic blood pressure, serum potassium and phosphate, serum albumin, and C reactive protein. [ABSTRACT FROM AUTHOR]

In patients with enhanced risk for bleeding, heparin‐free hemodialysis (HD) with conventional dialyzers is routinely used. To explore the potential benefit of using heparin‐coated dialyzers, we used a reference CT‐scanning technique and registered different clotting parameters to quantify coagulation with heparin‐coated versus non‐coated dialyzers. Six HD patients with thrombocytopenia were dialyzed 240 min in a randomized crossover study with Evodial 1.3 or FX600 Cordiax, each without anticoagulation. Blood samples were taken from the vascular access predialysis, and from the dialyzer inlet and outlet at 5 and 240 min after dialysis start. Predialysis blood samples were analyzed for hemoglobin, hematocrit, thrombocytes, fibrinogen, and activated partial thromboplastin time. On dialyzer inlet and outlet blood samples, a viscoelastic measurement of blood coagulation was performed using a Sonoclot analyzer. After dialysis, dialyzers were visually scored, subsequently dried for 24 h, weighed, and scanned with micro‐CT at a resolution of 25 µm. After image reconstruction, the open, non‐coagulated fibers were counted in a representative cross‐section at the dialyzer outlet. No sessions were terminated prematurely for circuit clotting. Heparin‐coated dialyzers had more patent fibers on micro‐CT versus non‐coated dialyzers and also had a better score of subjective visual assessment of fiber clotting. There was no difference in subjective assessment of clotting at the venous drip chamber. With both dialyzers, all ACT values remained in the normal range, and were lower at the dialyzer outlet versus inlet. In conclusion, dialysis with a heparin‐coated versus non heparin‐coated membrane results in substantially less coagulated fibers during 4 h hemodialysis without systemic anticoagulation. Eventual leaching of heparin, immobilized on the fiber membrane, does not result in measurable systemic anticoagulation. [ABSTRACT FROM AUTHOR]

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Background: Clinical trials are most informative for evidence-based decision-making when they consistently measure and report outcomes of relevance to stakeholders, especially patients, clinicians, and policy makers. However, sometimes terminology used is interpreted differently by different stakeholders, which might lead to confusion during shared decision making. The construct dialysis adequacy is frequently used, suggesting it is an important outcome both for health care professionals as for patients. Objective: To assess the scope and consistency of the construct dialysis adequacy as reported in randomised controlled trials in hemodialysis, and evaluate whether these align to the insights and understanding of this construct by patients. Methods: To assess scope and consistency of dialysis adequacy by professionals, we performed a systematic review searching the Cochrane Central Register of Controlled Trials (CENTRAL) up to July 2017. We identified all randomised controlled trails (RCT) including patients on hemodialysis and reporting dialysis adequacy, adequacy or adequacy of dialysis and extracted and classified all reported outcomes. To explore interpretation and meaning of the construct of adequacy by patients, we conducted 11 semi-structured interviews with HD patients using thematic analysis. Belgian registration number B670201731001. Findings: From the 31 included trials, we extracted and classified 98 outcome measures defined by the authors as adequacy of dialysis, of which 94 (95%) were biochemical, 3 (3%) non-biochemical surrogate and 2 (2%) patient-relevant. The three most commonly reported measures were all biochemical. None of the studies defined adequacy of dialysis as a patient relevant outcome such as survival or quality of life. Patients had a substantially different understanding of the construct dialysis adequacy than the biochemical interpretation reported in the literature. Being alive, time spent while being on dialysis, fatigue and friendliness of staff were the most prominent themes that patients linked to the construct of dialysis adequacy. Conclusion: Adequacy of dialysis as reported in the literature refers to biochemical outcome measures, most of which are not related with patient relevant outcomes. For patients, adequate dialysis is a dialysis that enables them to spend as much quality time in their life as possible. [ABSTRACT FROM AUTHOR]

Background: There is a gradual increase in serum concentrations of protein-bound colon-derived uremic toxins indoxyl sulphate (IxS) and p-cresyl sulphate (pCS) as chronic kidney disease (CKD) progresses. In acute kidney injury (AKI), up till now, the retention pattern has not been studied.Methods: In this study, 194 adult patients admitted with sepsis to the intensive care unit were included. IxS, pCS and serum creatinine (sCrea) were quantified at inclusion (D0) and at day 4, unless follow-up ended earlier (Dend).Results: Serum levels of sCrea (P < 0.001), IxS (P < 0.001) and pCS (P < 0.05) were higher in patients with AKI according to RIFLE classification at D0. In contrast with sCrea, IxS and pCS levels only increased from stage I (IxS) and F (pCS) on. When grouped according to evolution in RIFLE class from D0 to Dend, all solute concentrations were higher (P < 0.001) in the group with unfavourable evolution. In this group, there was a marked rise in sCrea (P < 0.001), a moderate one for pCS (P < 0.05), but no change for IxS (P = 0.112). There was a decrease (P < 0.001) of all solute concentrations in the group with favourable evolution. Comparing AKI with CKD patients matched for sCrea, total levels of both IxS and pCS were higher (P < 0.01) in patients with CKD.Conclusions: Although concentrations of IxS and pCS both tend to rise in sepsis patients with AKI, their evolution does not conform with that of sCrea. For the same level of sCrea, IxS and pCS concentrations are lower in AKI compared with CKD. [ABSTRACT FROM AUTHOR]

Background: After transplantation, cell-free DNA derived from the donor organ (ddcfDNA) can be detected in the recipient’s circulation. We aimed to quantify ddcfDNA levels in plasma of kidney transplant recipients thereby investigating the kinetics of this biomarker after transplantation and determining biological variables that influence ddcfDNA kinetics in stable and non-stable patients. Materials and methods: From 107 kidney transplant recipients, plasma samples were collected longitudinally after transplantation (day 1–3 months) within a multicenter set-up. Cell-free DNA from the donor was quantified in plasma as a fraction of the total cell-free DNA by next generation sequencing using a targeted, multiplex PCR-based method for the analysis of single nucleotide polymorphisms. A subgroup of stable renal transplant recipients was identified to determine a ddcfDNA threshold value. Results: In stable transplant recipients, plasma ddcfDNA% decreased to a mean (SD) ddcfDNA% of 0.46% (± 0.21%) which was reached 9.85 (± 5.6) days after transplantation. A ddcfDNA threshold value of 0.88% (mean + 2SD) was determined in kidney transplant recipients. Recipients that did not reach this threshold ddcfDNA value within 10 days after transplantation showed a higher ddcfDNA% on the first day after transplantation and demonstrated a higher individual baseline ddcfDNA%. Conclusion: In conclusion, plasma ddcfDNA fractions decreased exponentially within 10 days after transplantation to a ddcfDNA threshold value of 0.88% or less. To investigate the role of ddcfDNA for rejection monitoring of the graft, future research is needed to determine causes of ddcfDNA% increases above this threshold value. [ABSTRACT FROM AUTHOR]