Protein-bound uremic toxins (PBUTs) play a role in the multisystem disease that children on hemodialysis (HD) are facing, but little is known about their levels and protein binding (%PB). In this study, we evaluated the levels and %PB of six PBUTs cross-sectionally in a large pediatric HD cohort (n = 170) by comparing these with healthy and non-dialysis chronic kidney disease (CKD) stage 4–5 (n = 24) children. In parallel β2-microglobulin (β2M) and uric acid (UA) were evaluated. We then explored the impact of age and residual kidney function on uremic toxin levels and %PB using analysis of covariance and Spearman correlation coefficients (r_s). We found higher levels of β2M, p-cresyl glucuronide (pCG), hippuric acid (HA), indole acetic acid (IAA), and indoxyl sulfate (IxS) in the HD compared to the CKD4–5 group. In the HD group, a positive correlation between age and pCG, HA, IxS, and pCS levels was shown. Residual urine volume was negatively correlated with levels of β2M, pCG, HA, IAA, IxS, and CMPF (r_s −0.2 to −0.5). In addition, we found overall lower %PB of PBUTs in HD versus the CKD4–5 group, and showed an age-dependent increase in %PB of IAA, IxS, and pCS. Furhtermore, residual kidney function was overall positively correlated with %PB of PBUTs. In conclusion, residual kidney function and age contribute to PBUT levels and %PB in the pediatric HD population.

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.

Purpose Since 1997, strong incentives have been introduced worldwide to improve access to safe and effective medicines addressing the therapeutic needs of children. ACE inhibitors, the most prescribed antihypertensive drugs in the paediatric population, are one of the prototype drugs targeted by the legislation initiatives. Our purpose in assembling this review is to evaluate and describe the current evidence for the efficacy and safety profile of ACE inhibitors in the paediatric population. Methods The authors made a descriptive review of the literature from 1980 to 2015 using the following search terms: hypertension, child, paediatric, ACE (inhibitors), renin–angiotensin aldosterone system, captopril, lisinopril, enalapril, ramipril and fosinopril. Results A total of 16 studies evaluating efficacy and safety of ACE inhibitors were included in this review. The included studies demonstrate that ACE inhibitors have the potency to decrease the systolic and/or diastolic blood pressure with an overall favourable safety profile in a short-term period. More importantly, the incentives resulted in an improvement of the overall availability of paediatric labelling, dosing and safety information for ACE inhibitors. However, they failed to fulfil several of paediatric needs: absence of long-term safety data on growth and maturation, absence of commercially available child-friendly formulations and incomplete evaluation of the entire paediatric hypertension population. Conclusion Additional efforts are needed to close the gap between the availability of drugs that are labelled and indicated for paediatric use and the actual drug usage in children, especially in young children, neonates and children with severe hypertension, renal transplantation or severe renal impairment.

While it is widely accepted that the nutritional management of the infant with chronic kidney disease (CKD) is paramount to achieve normal growth and development, nutritional management is also of importance beyond 1 year of age, particularly in toddlers, to support the delayed infantile stage of growth that may extend to 2–3 years of age. Puberty is also a vulnerable period when nutritional needs are higher to support the expected growth spurt. Inadequate nutritional intake throughout childhood can result in failure to achieve full adult height potential, and there is an increased risk for abnormal neurodevelopment. Conversely, the rising prevalence of overweight and obesity among children with CKD underscores the necessity for effective nutritional strategies to mitigate the risk of metabolic syndrome that is not confined to the post-transplant population. Nutritional management is of primary importance in improving metabolic equilibrium and reducing CKD-related imbalances, particularly as the range of foods eaten by the child widens as they get older (including increased consumption of processed foods), and as CKD progresses. The aim of this review is to integrate the Pediatric Renal Nutrition Taskforce (PRNT) clinical practice recommendations (CPRs) for children (1–18 years) with CKD stages 2–5 and on dialysis (CKD2–5D). We provide a holistic approach to the overall nutritional management of the toddler, child, and young person. Collaboration between physicians and pediatric kidney dietitians is strongly advised to ensure comprehensive and tailored nutritional care for children with CKD, ultimately optimizing their growth and development. Graphical

Background: Haemodiafiltration (HDF) is accepted to effectively lower plasma levels of middle molecules in the long term, while data are conflicting with respect to the additive effect of convection on lowering protein-bound uraemic toxins (PBUTs). Here we compared pre-dialysis β2-microglobulin (β2M) and PBUT levels and the percentage of protein binding (%PB) in children on post-dilution HDF versus conventional high- (hf) or low-flux (lf) haemodialysis (HD) over 12 months of treatment.Methods: In a prospective multicentre, non-randomized parallel-arm intervention study, pre-dialysis levels of six PBUTs and β2M were measured in children (5–20 years) on post-HDF (n = 37), hf-HD (n = 42) and lf-HD (n = 18) at baseline and after 12 months. Analysis of variance was used to compare levels and %PB in post-HDF versus conventional hf-HD and lf-HD cross-sectionally at 12 months and longitudinal from baseline to 12 months.Results: For none of the PBUTs, no difference was found in either total and free plasma levels or %PB between post-HDF versus the hf-HD and lf-HD groups. Children treated with post-HDF had lower pre-dialysis β2M levels [median 23.2 (21.5; 26.6) mg/dL] after 12 months versus children on hf-HD [P<0.01; 35.2 (29.3; 41.2) mg/dL] and children on lf-HD [P<0.001; 47.2 (34.3; 53.0) mg/dL]. While β2M levels remained steady in the hf-HD and lf-HD group, a decrease in β2M was demonstrated for children on post-HDF (P<0.01).Conclusions: While post-HDF successfully decreased β2M, no additive effect on PBUT over 12 months of treatment was found. PBUT removal is complex and hampered by several factors. In children, these factors might be different from adults and should be explored in future research.