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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.
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Taxa de Filtração Glomerular , Insuficiência Renal Crônica , Toxinas Urêmicas , Humanos , Criança , Insuficiência Renal Crônica/sangue , Masculino , Feminino , Adolescente , Pré-Escolar , Estudos LongitudinaisRESUMO
Introduction: Growth failure is considered the most important clinical outcome parameter in childhood chronic kidney disease (CKD). Central to the pathophysiology of growth failure is the presence of a chronic proinflammatory state, presumed to be partly driven by the accumulation of uremic toxins. In this study, we assessed the association between uremic toxin concentrations and height velocity in a longitudinal multicentric prospective pediatric CKD cohort of (pre)school-aged children and children during pubertal stages. Methods: In a prospective, multicentric observational study, a selection of uremic toxin levels of children (aged 0-18 years) with CKD stage 1 to 5D was assessed every 3 months (maximum 2 years) along with clinical growth parameters. Linear mixed models with a random slope for age and a random intercept for child were fitted for height (in cm and SD scores [SDS]). A piecewise linear association between age and height was assumed. Results: Data analysis included data from 560 visits of 81 children (median age 9.4 years; 2/3 male). In (pre)school aged children (aged 2-12 years), a 10% increase in concurrent indoxyl sulfate (IxS, total) concentration resulted in an estimated mean height velocity decrease of 0.002 SDS/yr (P < 0.05), given that CKD stage, growth hormone (GH), bicarbonate concentration, and dietary protein intake were held constant. No significant association with height velocity was found in children during pubertal stages (aged >12 years). Conclusion: The present study demonstrated that, especially IxS contributes to a lower height velocity in (pre)school children, whereas we could not find a role for uremic toxins with height velocity during pubertal stages.
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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.
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Ansiedade , Depressão , Saúde Mental , Pais , Insuficiência Renal Crônica , Estresse Psicológico , Humanos , Feminino , Masculino , Pais/psicologia , Estudos Transversais , Criança , Insuficiência Renal Crônica/psicologia , Insuficiência Renal Crônica/terapia , Pré-Escolar , Estresse Psicológico/etiologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Estresse Psicológico/diagnóstico , Adulto , Depressão/epidemiologia , Depressão/etiologia , Depressão/psicologia , Depressão/diagnóstico , Ansiedade/psicologia , Ansiedade/epidemiologia , Ansiedade/etiologia , Ansiedade/diagnóstico , Adolescente , Lactente , Inquéritos e Questionários , Pessoa de Meia-Idade , Recém-Nascido , Poder Familiar/psicologia , Estudos de Casos e ControlesRESUMO
Background: During extended (nocturnal) hemodialysis (ENHD), the dose of low-molecular-weight heparin (LMWH) can be administered as a single injection or as a divided dose over different time points. Our hypothesis was that a single injection might be sufficient to maintain dialyzer fiber patency. In addition, we investigated whether the biochemical clotting parameter anti-Xa accurately predicts fiber blocking. Methods: Our hypothesis was tested in 20 stable patients on ENHD in a random cross-over setting during two consecutive midweek sessions. The regular total dose of LMWH (i.e. enoxaparin, Clexane® 40-100 mg, Sanofi, Belgium) was either given (i) in a single injection at the dialysis start or (ii) divided over two injections, at the start and halfway the dialysis session. Blood samples were taken from the arterial blood line at different time points to determine plasma anti-Xa activity levels. Post-dialysis, the rinsed and dried hemodialyzers were scanned with a reference micro-computed tomography (µCT) scanning technique, and non-blocked fibers were counted in a central cross-section of the dialyzer outlet potting (ImageJ, NIH, USA). Results: The percentage of open fibers in the dialyzers after a single injection of LMWH [91 (61-96)%] versus divided administration [94 (79-98)%] was not different. Time averaged anti-Xa activity levels were clinically not significantly different between both sessions. Anti-Xa activity levels correlated with the administered anticoagulation doses normalized for body weight, but not with the percentages open fibers in the dialyzers. Conclusion: Our results indicate that there is no need to administer enoxaparin over two injections for ENHD up to 8 h. The usefulness of monitoring anti-Xa levels to predict fiber patency, assessed by µCT, can be questioned, but further clinical trials are needed.
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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.
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Contusões , Qualidade de Vida , Humanos , Estudos Prospectivos , Diálise Renal/efeitos adversos , Hematoma , Anticoagulantes/uso terapêuticoRESUMO
BACKGROUND: This cross-sectional study investigated quality of life (QoL) and illness-related parental stress in children with kidney diseases by (1) comparing mean levels of these two variables between several kidney disease categories; (2) exploring correlations between QoL and parental stress; and (3) describing which disease category reports lowest QoL and highest parental stress. METHODS: We included 295 patients with a kidney disease (0-18 years) and their parents, followed at 6 reference centers for pediatric nephrology. Children's QoL was assessed by the PedsQL™ 4.0 Generic Core Scales, and illness-related stress by the Pediatric Inventory for Parents. All patients were divided into 5 kidney disease categories according to the multidisciplinary care program criteria prescribed by the Belgian authorities: (1) structural kidney diseases, (2) tubulopathies and metabolic diseases, (3) nephrotic syndrome, (4) acquired diseases with proteinuria and hypertension, and (5) kidney transplantation. RESULTS: Child self-reports showed no differences in QoL between kidney disease categories, in contrast to parent proxy reports. Parents of transplant patients reported lower QoL in their child and more parental stress compared with the 4 non-transplant categories. QoL and parental stress were negatively correlated. Lowest QoL and highest parental stress scores were mainly found in transplant patients. CONCLUSIONS: This study showed lower QoL and higher parental stress in pediatric transplant patients compared with non-transplants, based on parent reports. Higher parental stress is associated with worse QoL in the child. These results highlight the importance of multidisciplinary care for children with kidney diseases, with special attention to transplant patients and their parents. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Nefropatias , Qualidade de Vida , Criança , Humanos , Estudos Transversais , Procurador , Nefropatias/terapia , Pais , Inquéritos e QuestionáriosRESUMO
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.
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Qualidade de Vida , Diálise Renal , Força da Mão , Humanos , Desempenho Físico Funcional , Modelos de Riscos ProporcionaisRESUMO
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.
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Diálise Renal , Toxinas Biológicas , Coagulação Sanguínea , Estudos Cross-Over , HumanosRESUMO
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.
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Potássio na Dieta , Insuficiência Renal Crônica , Criança , Fibras na Dieta , Humanos , Potássio , Estudos Prospectivos , Diálise Renal , Insuficiência Renal Crônica/terapiaRESUMO
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.
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Falência Renal Crônica , Insuficiência Renal Crônica , Bélgica , Criança , Estudos Transversais , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Masculino , Pais , Qualidade de Vida , Insuficiência Renal Crônica/diagnóstico , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Dialysis patients experience a high burden of physical and emotional symptoms directly affecting their sleep and quality of life. In this study, objective and subjective measurements to quantify sleep were performed, compared with those of healthy controls, and associated with burden of comorbidity and uraemic toxicity. METHODS: A total of 64 dialysis patients were included-10 peritoneal dialysis, 42 in-centre daytime haemodialysis (HD) and 12 in-centre nocturnal HD patients-as well as one-to-one age- and gender-matched healthy controls. Assumed and actual sleep time, sleep efficiency and fragmentation index were measured by actigraphy for at least two consecutive nights. Patients and controls also completed Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) questionnaires. The patients' blood was sampled to determine concentrations of a representative series of uraemic toxins and the Davies-Stoke comorbidity index was derived from medical records. RESULTS: Apart from the assumed sleep time, all objectively and subjectively measured sleep parameters were worse in the dialysis group compared with the healthy controls. No differences were seen in any of the measured sleep parameters among the different dialysis groups. None of the objectively measured sleep parameters were associated with ISI or PSQI scores in dialysis patients, while sleep times were related to the subjective scores in the healthy cohort. Objectively assessed sleep parameters were associated to neither the uraemic toxicity load nor the Davies-Stoke score. CONCLUSIONS: Independent of the modality, dialysis patients have sleep quality much worse than age- and gender-matched healthy controls. The objectively measured sleep parameters could not be associated to the subjective score, uraemic toxicity or comorbidity score, highlighting the need for objective measurements of sleep and clinical guidelines to aid patient management.
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Therapeutic apheresis (TA) is prescribed to patients that suffer from a severe progressive disease that is not sufficiently treated by conventional medications. A way to gain more knowledge about this treatment is usually by the local analysis of data. However, the use of large quality assessment registries enables analyses of even rare findings. Here, we report some of the recent data from the World Apheresis Association (WAA) registry. Data from >104,000 procedures were documented, and TA was performed on >15,000 patients. The main indication for TA was the collection of autologous stem cells (45% of patients) as part of therapy for therapy. Collection of stem cells from donors for allogeneic transplantation was performed in 11% of patients. Patients with indications such as neurological diseases underwent plasma exchange (28%). Extracorporeal photochemotherapy, lipid apheresis, and antibody removal were other indications. Side effects recorded in the registry have decreased significantly over the years, with approximately only 10/10,000 procedures being interrupted for medical reasons. CONCLUSION: Collection of data from TA procedures within a multinational and multicenter concept facilitates the improvement of treatment by enabling the analysis of and feedback on indications, procedures, effects, and side effects.
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BACKGROUND: While systemic anticoagulation is most widely used in haemodialysis (HD), contraindications to its use might occur in particular settings. The Solacea™ haemodialyser with an asymmetric triacetate membrane claims improved biocompatibility and has already shown promising results when used in combination with only half dose of anticoagulation. To quantify the performance of the Solacea™ when further decreasing anticoagulation to zero, fibre blocking was assessed by micro-computed tomography (micro-CT). METHODS: Ten maintenance HD patients underwent six dialysis sessions at midweek using a Solacea™ 19H dialyser, consecutively in pre-dilution haemodiafiltration (pre-HDF), HD and post-dilution HDF (post-HDF). After the first three sessions with only a quarter of their regular anticoagulation dose (one-quarter), the last three sessions were performed without anticoagulation (zero). Dialyser fibre blocking was quantified in the dialyser outlet potting using a 3D micro-CT scanning technique post-dialysis. RESULTS: Even in case of reduced (one-quarter) anticoagulation, the relative number of open fibres post-dialysis was almost optimal, i.e. 0.96 (0.87-0.99) with pre-HDF, 0.99 (0.97-0.99) with HD and 0.97 (0.92-0.99) with post-HDF. Fibre patency was mildly decreased for pre-HDF and HD when anticoagulation was decreased from one-quarter to zero, i.e. to 0.76 (0.61-0.85) with pre-HDF (P = 0.004) and to 0.80 (0.77-0.89) with HD (P = 0.013). Comparing the results for zero anticoagulation, post-HDF [i.e. 0.94 (0.82-0.97)] performed as well as HD and pre-HDF. CONCLUSIONS: The Solacea™ dialyser provides promising results for use in conditions where systemic anticoagulation is contraindicated. Post-HDF, although inducing haemoconcentration in the dialyser, is equally effective for fibre patency in case of zero anticoagulation as pre-HDF and HD when using Solacea™.
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Acute neonatal hyperammonemia is associated with poor neurological outcomes and high mortality. We developed, based on kinetic modeling, a user-friendly and widely applicable algorithm to tailor the treatment of acute neonatal hyperammonemia. A single compartmental model was calibrated assuming a distribution volume equal to the patient's total body water (V), as calculated using Wells' formula, and dialyzer clearance as derived from the measured ammonia time-concentration curves during 11 dialysis sessions in four patients (3.2 ± 0.4 kg). Based on these kinetic simulations, dialysis protocols could be derived for clinical use with different body weights, start concentrations, dialysis machines/dialyzers and dialysis settings (e.g., blood flow QB). By a single measurement of ammonia concentration at the dialyzer inlet and outlet, dialyzer clearance (K) can be calculated as K = QBâ[(Cinlet - Coutlet)/Cinlet]. The time (T) needed to decrease the ammonia concentration from a predialysis start concentration Cstart to a desired target concentration Ctarget is then equal to T = (-V/K)âLN(Ctarget/Cstart). By implementing these formulae in a simple spreadsheet, medical staff can draw an institution-specific flowchart for patient-tailored treatment of hyperammonemia.
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Algoritmos , Hiperamonemia/terapia , Amônia/sangue , Modelos Epidemiológicos , Humanos , Recém-Nascido , Cinética , Diálise Renal/métodos , Ureia/sangueRESUMO
Imbalanced colonic microbial metabolism plays a pivotal role in generating protein-bound uraemic toxins (PBUTs), which accumulate with deteriorating kidney function and contribute to the uraemic burden of children with chronic kidney disease (CKD). Dietary choices impact the gut microbiome and metabolism. The aim of this study was to investigate the relation between dietary fibre and gut-derived PBUTs in paediatric CKD. Sixty-one (44 male) CKD children (9 ± 5 years) were prospectively followed for two years. Dietary fibre intake was evaluated by either 24-h recalls (73%) or 3-day food records (27%) at the same time of blood sampling for assessment of total and free serum levels of different PBUTs using liquid chromatography. We used linear mixed models to assess associations between fibre intake and PBUT levels. We found an inverse association between increase in fibre consumption (g/day) and serum concentrations of free indoxyl sulfate (-3.1% (-5.9%; -0.3%) (p = 0.035)), free p-cresyl sulfate (-2.5% (-4.7%; -0.3%) (p = 0.034)), total indole acetic acid (IAA) (-1.6% (-3.0%; -0.3%) (p = 0.020)), free IAA (-6.6% (-9.3%; -3.7%) (p < 0.001)), total serum p-cresyl glucuronide (pCG) (-3.0% (-5.6%; -0.5%) (p = 0.021)) and free pCG levels (-3.3% (-5.8%; -0.8%) (p = 0.010)). The observed associations between dietary fibre intake and the investigated PBUTs highlight potential benefits of fibre intake for the paediatric CKD population. The present observational findings should inform and guide adaptations of dietary prescriptions in children with CKD.
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Bactérias/metabolismo , Fibras na Dieta/administração & dosagem , Microbioma Gastrointestinal , Intestinos/microbiologia , Insuficiência Renal Crônica/dietoterapia , Toxinas Biológicas/sangue , Uremia/dietoterapia , Adolescente , Fatores Etários , Bélgica , Criança , Pré-Escolar , Disbiose , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/microbiologia , Uremia/sangue , Uremia/diagnóstico , Uremia/microbiologiaRESUMO
[This corrects the article DOI: 10.1093/ckj/sfz163.][This corrects the article DOI: 10.1093/ckj/sfz163.].
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BACKGROUND: Different strategies can be used to counteract coagulation of extracorporeal systems. Systemic anticoagulation is most widely used in routine clinical practice, but can be contraindicated in specific settings. The Solacea™ dialyser, containing the asymmetric triacetate membrane, claims improved biocompatibility, which should result in decreased tendency for coagulation. We quantified the performance of the Solacea™ versus the FX800CORDIAX dialyser regarding resistance to fibre blocking as assessed by micro-computed tomography (CT). METHODS: This cross-over study with four arms randomized consecutively 10 maintenance haemodialysis patients to a 4-h post-dilution haemodiafiltration session at midweek, using either Solacea™ 19 H or FX800CORDIAX, with either regular or half dose of anticoagulation (EC2017/1459-NCT03820401). Dialyser fibre blocking was visualized in the dialyser outlet potting using a 3D CT scanning technique on micrometre resolution. Extraction ratios of middle molecules [myoglobin, lambda and kappa free light chains (FLCs)] were determined. RESULTS: The relative number of open fibres post-dialysis was lower in FX800CORDIAX versus Solacea™ dialyser, and this was irrespective of the anticoagulation dose used or the threshold for counting open fibres. Extraction ratios of FLCs were not different at regular anticoagulation between Solacea™ and FX800CORDIAX (21% ± 4% for kappa and 32% ± 8% for lambda with Solacea™ versus 23% ± 7% and 38% ± 6% for FX800CORDIAX), but were superior with the Solacea™ (34% ± 12% versus 22% ± 8% with FX800CORDIAX; P = 0.02) for myoglobin in case of halving anticoagulation dose. No clinically relevant albumin loss was detected. CONCLUSIONS: The Solacea™ dialyser seems to be promising for use in conditions where systemic anticoagulation is contraindicated, as even under conditions of low systemic anticoagulation, virtually no signs of fibre blocking could be observed using the sensitive micro-CT scanning technique. This finding is in line with its presumed good performance in terms of biocompatibility.
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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.
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Insuficiência Renal Crônica , Uremia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Fibras na Dieta , Humanos , Toxinas Biológicas , Toxinas UrêmicasRESUMO
The evidence on impact of intradialytic exercise on the removal of urea, is conflictive. Impact of exercise on kinetics of serum levels of protein-bound uraemic toxins, known to exert toxicity and to have kinetics dissimilar of those of urea, has so far not been explored. Furthermore, if any effect, the most optimal intensity, time point and/or required duration of intradialytic exercise to maximise removal remain obscure. We therefore studied the impact of different intradialytic cycling schedules on the removal of protein-bound uraemic toxins during haemodialysis (HD).This randomised cross-over study included seven stable patients who were dialysed with an FX800 dialyser during three consecutive midweek HD sessions of 240 min: (A) without cycling; (B) cycling for 60 min between 60th and 120th minutes of dialysis; and (C) cycling for 60 min between 150th and 210th minutes, with the same cycling load as in session B. Blood and dialysate flows were respectively 300 and 500 mL/min. Blood was sampled from the blood inlet at different time points, and dialysate was partially collected (300 mL/h). Small water soluble solutes and protein-bound toxins were quantified and intradialytic reduction ratios (RR) and overall removal were calculated per solute.Total solute removal and reduction ratios were not different between the three test sessions, except for the reduction ratios RR60-120 and RR150-210 for potassium.In conclusion, we add evidence to the existing literature that, regardless of the timing within the dialysis session, intradialytic exercise has no impact on small solute clearance, and demonstrated also a lack of impact for protein-bound solutes.