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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 m.sup.2 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. Graphical abstract A higher-resolution version of the graphical abstract is available as Supplementary information., Author(s): Amina El Amouri [sup.1] , Kato Delva [sup.2] , Aurélie Foulon [sup.2] , Charlotte Vande Moortel [sup.2] , Koen Van Hoeck [sup.3] , Griet Glorieux [sup.2] , Wim Van [...]

Background Children with chronic kidney disease (CKD) have a low quality of life (QoL). The PedsQL[TM] 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[TM] 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[TM] 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 ([alpha]'s) for the PedsQL[TM] 3.0 ESRD Module demonstrated excellent reliability for the Total Scale scores. For all 7 subscales, [alpha]'s were greater than 0.60, except for Perceived Physical Appearance. Overall, intercorrelations with the PedsQL[TM] 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[TM] 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. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information., Author(s): Elke De Bruyne [sup.1] , Sunny Eloot [sup.2] , Johan Vande Walle [sup.3] , Ann Raes [sup.3] , Wim Van Biesen [sup.2] , Liesbet Goubert [sup.4] , Tine Vervoort [...]

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]

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, Author(s): Amina El Amouri [sup.1] , Evelien Snauwaert [sup.1] , Aurélie Foulon [sup.2] , Charlotte Vande Moortel [sup.2] , Maria Van Dyck [sup.3] , Koen Van Hoeck [sup.4] , Nathalie [...]

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]

Author(s): Evelien Snauwaert [sup.1] , Wim Van Biesen [sup.2] , Ann Raes [sup.3] , Griet Glorieux [sup.2] , Raymond Vanholder [sup.2] , Johan Vande Walle [sup.3] , Sunny Eloot [sup.2] [...]

Background Chronic kidney disease (CKD) in childhood is characterised by the accumulation of uraemic toxins resulting in a multisystem disorder that has a negative impact on quality of life. Childhood CKD is predominantly defined by a decrease in glomerular filtration rate, estimated (eGFR) by a single serum measurement of endogenous biomarkers, e.g. creatinine. The objective of this study was to evaluate how accurately eGFR predicts the concentration of uraemic toxins in a paediatric CKD cohort. Methods In 65 children (10.8 [5.1; 14.7] years) with CKD (eGFR 44 [20; 64] mL/min/1.73 m.sup.2), serum concentrations were determined of small solutes (uric acid [UA], urea, symmetric dimethylarginine [SDMA], asymmetric dimethylarginine [ADMA]), middle molecules ([beta]2-microglobulin [[beta]2M], complement factor D [CfD]) and protein-bound solutes (p-cresylglucuronide [pCG], hippuric acid, indole acetic acid, indoxyl sulphate [IxS], p-cresylsulfate [pCS] and 3-carboxy-4-methyl-5-propyl-furanpropionic acid [CMPF]). Spearman's correlation coefficients (r) were calculated to correlate uraemic toxin concentrations with three different eGFR equations, based on either serum creatinine or [beta]2M. Results Updated Schwartz eGFR was correlated reasonably well with concentrations of creatinine (r = -0.98), urea (r.sub.s = -0.84), SDMA (r = -0.82) and middle molecules CfD and [beta]2M (both r.sub.s = -0.90). In contrast, poor correlation coefficients were found for CMPF (r.sub.s = -0.32), UA (r.sub.s = -0.45), ADMA (r.sub.s = -0.47) and pCG (r.sub.s = -0.48). The other toxins, all protein-bound, had r.sub.s between -0.75 and -0.57. Comparable correlations were found between the three evaluated eGFR equations and uraemic toxin concentrations. Conclusions This study demonstrates that eGFR poorly predicts concentrations of protein-bound uraemic toxins, UA and ADMA in childhood CKD. Therefore, eGFR only partially reflects the complexity of the accumulation pattern of uraemic toxins in childhood CKD., Author(s): Evelien Snauwaert [sup.1] , Wim Van Biesen [sup.2] , Ann Raes [sup.3] , Els Holvoet [sup.2] , Griet Glorieux [sup.2] , Koen Van Hoeck [sup.4] , Maria Van Dyck [...]

Evidence-based medicine (EBM) is gaining importance in the current paediatric healthcare landscape. Improvement of paediatric health status is its major aim. However, for EBM to be successful, all stakeholders involved should understand what EBM really is, why and how EBM should or should not be practiced, and have the necessary skills to distinguish methodologically sound papers from biased opinion papers, and understand how and why guidelines are different from systematic reviews. Improving patient outcome requires attention to high-quality evidence and understanding of the processes of medical decision-making. Rigorous methodology is the cornerstone of guideline production, but in cases where quality evidence cannot be produced, as is often the case in paediatric nephrology because of low patient numbers, consensus-based guidance may be suitable to assist the practitioner at the bedside, as long as the underlying process is transparent. Most importantly, EBM should support patient involvement in a shared decision-making process. The more consistent and accurately predictable the effect of certain interventions is, clinically relevant to patients rather than affecting surrogate outcomes, and a priority for patients and other stakeholders, the more likely it is that adherence to the guidance provided will improve the outcome of patients., Author(s): Evelien Snauwaert [sup.1] , Johan VandeWalle [sup.1] , Evi V. Nagler [sup.2] [sup.3] , Wim Van Biesen [sup.2] [sup.3] Author Affiliations: (1) Department of Paediatric Nephrology, Ghent University Hospital, [...]

In this review we summarize the world-wide epidemiology of acute kidney injury (AKI) in children with special emphasis on low-income countries, notably those of the sub-Saharan continent. We discuss definitions and classification systems used in pediatric AKI literature. At present, despite some shortcomings, traditional Pediatric Risk Injury Failure Loss and End Stage Kidney Disease (pRIFLE) and Kidney Disease Improving Global Outcomes (KDIGO) systems are the most clinically useful. Alternative definitions, such as monitoring serum cystatin or novel urinary biomarkers, including cell cycle inhibitors, require more long-term studies in heterogenous pediatric AKI populations before they can be recommended in routine clinical practice. A potentially interesting future application of some novel biomarkers could be incorporation into the 'renal angina index', a concept recently introduced in pediatric nephrology. The most reliable epidemiological data on AKI in children come from high-outcome countries and are frequently focused on critically ill pediatric intensive care unit populations. In these patients AKI is often secondary to other systemic illnesses or their treatment. Based on a recent literature search performed within the framework of the 'AKI 0by25' project of the International Society of Nephrology, we discuss the scarce and often inaccurate data on AKI epidemiology in low-income countries, notably those on the African continent. The last section reflects on some of the many barriers to improvement of overall health care in low-income populations. Although preventive strategies for AKI in low-income countries should essentially be the same as those in high-income countries, we believe any intervention for earlier detection and better treatment of AKI must address all health determinants, including educational, cultural, socio-economic and environmental factors, specific for these deprived areas., Author(s): Norbert Lameire [sup.1] , Wim Van Biesen [sup.1] , Raymond Vanholder [sup.1] Author Affiliations: (1) 0000 0004 0626 3303grid.410566.0Renal Division, Department of Medicine, University Hospital, De Pintelaan 285, 9000, [...]