Assessment and management of vitamin status in children with CKD stages 2-5, on dialysis and post-transplantation: clinical practice points from the Pediatric Renal Nutrition Taskforce.

Children with chronic kidney disease (CKD) are at risk for vitamin deficiency or excess. Vitamin status can be affected by diet, supplements, kidney function, medications, and dialysis. Little is known about vitamin requirements in CKD, leading to practice variation.The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric kidney dietitians and pediatric nephrologists, was established to develop evidence-based clinical practice points (CPPs) to address challenges and to serve as a resource for nutritional care. Questions were formulated using PICO (Patient, Intervention, Comparator, Outcomes), and literature searches undertaken to explore clinical practice from assessment to management of vitamin status in children with CKD stages 2-5, on dialysis and post-transplantation (CKD2-5D&T). The CPPs were developed and finalized using a Delphi consensus approach. We present six CPPs for vitamin management for children with CKD2-5D&T. We address assessment, intervention, and monitoring. We recommend avoiding supplementation of vitamin A and suggest water-soluble vitamin supplementation for those on dialysis. In the absence of evidence, a consistent structured approach to vitamin management that considers assessment and monitoring from dietary, physical, and biochemical viewpoints is needed. Careful consideration of the impact of accumulation, losses, comorbidities, and medications needs to be explored for the individual child and vitamin before supplementation can be considered. When supplementing, care needs to be taken not to over-prescribe. Research recommendations are suggested.

Mental health and professional outcomes in parents of children with chronic kidney disease.

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.

Transition in enuresis patients: Identifying the gaps and opportunities for the future.

BACKGROUND: Nocturnal enuresis is generally considered a children's condition, yet it may persist 1%-2% in adolescence and early adulthood. Refractory patients often demand follow-up by multidisciplinary teams, which is only restricted to some of the expert tertiary centers. However, there are no standardized transition programs/guidelines when follow-up must be passed from pediatric to adult healthcare providers. AIM, MATERIALS & METHODS: To investigate this issue, we conducted a literature search on enuresis transition, which resulted in no articles. We, therefore, proceeded in a rescue search strategy: we explored papers on transition programs of conditions that may be related and/or complicated by enuresis, nocturia, or other urinary symptoms (chronic diseases, CKD, bladder dysfunction, kidney transplant, neurogenic bladder). RESULTS: These programs emphasize the need for a multidisciplinary approach, a transition coordinator, and the importance of patient and parent participation, practices that could be adopted in enuresis. The lack of continuity in enuresis follow-up was highlighted when we investigated who was conducting research and publishing on enuresis and nocturia. Pediatric disciplines (50%) are mostly involved in children's studies, and urologists in the adult ones (37%). DISCUSSION: We propose a stepwise approach for the transition of children with enuresis from pediatric to adult care, depending on the clinical subtype: from refractory patients who demand more complex, multidisciplinary care and would benefit from a transition coordinator up to children/young adults cured of enuresis but who persist in having or present lower urinary tract symptoms (LUTS)/nocturia later on. In any case, the transition process should be initiated early at the age of 12-14 years, with adequate information to the patient and parents regarding relapses or LUTS/nocturia occurrence and of the future treating general practitioner on the enuresis characteristics and comorbidities of the patient.

Discontinuing absorbent pants in children with bedwetting: a randomized controlled trial.

The objective of this study is to examine the effect of discontinuing wearing protective garments (absorbent pyjama pants - APP) in children with severe childhood nocturnal enuresis (NE). The study employs a multicenter, parallel, randomized controlled trial. Following a 4-week run-in period, participants were randomly allocated in a 2:1 group allocation to discontinue or continue using APP. The research was conducted across seven European pediatric incontinence centers. The study included treatment-naïve children aged 4-8 years with severe (7/7 wet nights per week) mono-symptomatic NE, who had used nighttime protection for at least 6 months prior to the study. The study consisted of a 4-week run-in period (± 7 days), where all children slept wearing APP (DryNites®). At week 4 (± 7 days), if meeting randomization criteria (7/7 wet nights during the last week of run-in), participants were randomized to continue to sleep in APP or to discontinue their use for a further 4 weeks, with the option of another 4 weeks in the extension period. The primary outcome was the difference between groups of wet nights during the last week of intervention. Quality of life (QoL) and sleep were secondary endpoints. In total, 105 children (43 girls and 62 boys, mean age 5.6 years [SD 1.13]) were randomized (no-pants group n = 70, pants group n = 35). Fifteen children (21%) in the no-pants group discontinued early due to stress related to the intervention. Children in the no-pants group experienced fewer wet nights compared to the pants group during the last week (difference 2.3 nights, 95% CI 1.54-3.08; p < 0.0001). In the no-pants group, 20% responded to the intervention, of whom 13% had a full response. Clinical improvement was detected within 2 weeks. Sleep and QoL were reported as negatively affected by APP discontinuation in the extension period but not in the core period.    Conclusion: A ~ 10% complete resolution rate was associated with discontinuing APP. While statistically significant, the clinical relevance is debatable, and the intervention should be tried only if the family is motivated. Response was detectable within 2 weeks. Discontinuing APP for 4-8 weeks was reported to negatively affect QoL and sleep quality. No severe side effects were seen.Trial registration: Clinicaltrials.gov Identifier: NCT04620356; date registered: September 23, 2020. Registered under the name: "Effect of Use of DryNites Absorbent Pyjama Pants on the Rate of Spontaneous Resolution of Paediatric Nocturnal Enuresis (NE)."

Have We Neglected to Study Target-Site Drug Exposure in Children? A Systematic Review of the Literature.

BACKGROUND AND OBJECTIVE: Drug dosing should ideally be based on the drug concentrations at the target site, which, for most drugs, corresponds to the tissue. The exact influence of growth and development on drug tissue distribution is unclear. This systematic review compiles the current knowledge on the tissue distribution of systemically applied drugs in children, with the aim to identify priorities in tissue pharmacokinetic (PK) research in this population. METHODS: A systematic literature search was performed in the MEDLINE and Embase databases. RESULTS: Forty-two relevant articles were identified, of which 71% investigated antibiotics, while drug classes from the other studies were anticancer drugs, antifungals, anthelmintics, sedatives, thyreostatics, immunomodulators, antiarrhythmics, and exon skipping therapy. The majority of studies (83%) applied tissue biopsy as the sampling technique. Tonsil and/or adenoid tissue was most frequently examined (70% of all included patients). The majority of studies had a small sample size (median 9, range 1-93), did not include the youngest age categories (neonates and infants), and were of low reporting quality. Due to the heterogeneous data from different study compounds, dosing schedules, populations, and target tissues, the possibility for comparison of PK data between studies was limited. CONCLUSION: The influence of growth and development on drug tissue distribution continues to be a knowledge gap, due to the paucity of tissue PK data in children, especially in the younger age categories. Future research in this field should be encouraged as techniques to safely investigate drug tissue disposition in children are available.

Investigating the use of finerenone in children with chronic kidney disease and proteinuria: design of the FIONA and open-label extension studies.

INTRODUCTION: Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria. OBJECTIVE: FIONA and the associated open-label extension (OLE) study aim to demonstrate that combining finerenone with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) is safe, well-tolerated, and effective in sustainably reducing urinary protein excretion in children with CKD and proteinuria. DESIGN: FIONA (NCT05196035; Eudra-CT: 2021-002071-19) is a randomized (2:1), double-blind, placebo-controlled, multicenter, phase III study of 6 months' duration in approximately 219 pediatric patients. Patients must have a clinical diagnosis of CKD (an eGFR ≥ 30 mL/min/1.73 m2 if ≥ 1 to < 18 years or a serum creatinine level ≤ 0.40 mg/dL for infants 6 months to < 1 year) with significant proteinuria despite ACEi or ARB usage. The primary objective is to demonstrate that finerenone, added to an ACEi or ARB, is superior to placebo in reducing urinary protein excretion. FIONA OLE (NCT05457283; Eudra-CT: 2021-002905-89) is a single-arm, open-label study, enrolling participants who have completed FIONA. The primary objective of FIONA OLE is to provide long-term safety data. FIONA has two primary endpoints: urinary protein-to-creatinine ratio (UPCR) reduction of ≥ 30% from baseline to day 180 and percent change in UPCR from baseline to day 180. A sample size of 198 participants (aged 2 to < 18 years) in FIONA will provide at least 80% power to reject the null hypothesis of either of the two primary endpoints. CONCLUSION: FIONA is evaluating the use of finerenone in children with CKD and proteinuria. Should safety, tolerability, and efficacy be demonstrated, finerenone could become a useful additional therapeutic agent in managing proteinuria and improving kidney outcomes in children with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05196035. Registered on 19 January 2022.

Technical requirements and devices available for long-term hemodialysis in children-mind the gap!

Children requiring long-term kidney replacement therapy are a "rare disease" cohort. While the basic technical requirements for hemodialysis (HD) are similar in children and adults, key aspects of the child's cardiovascular anatomy and hemodynamic specifications must be considered. In this article, we describe the technical requirements for long-term HD therapy for children and the devices that are currently available around the world. We highlight the characteristics and major technical shortcomings of permanent central venous catheters, dialyzers, dialysis machines, and software available to clinicians who care for children. We show that currently available HD machines are not equipped with appropriately small circuits and sensitive control mechanisms to perform safe and effective HD in the youngest patients. Manufacturers limit their liability, and health regulatory agencies permit the use of devices, only in children according to the manufacturers' pre-specified weight limitations. Although registries show that 6-23% of children starting long-term HD weigh less than 15 kg, currently, there is only one long-term HD device that is cleared for use in children weighing 10 to 15 kg and none is available and labelled for use in children weighing less than 10 kg anywhere in the world. Thus, many children are being treated "off-label" and are subject to interventions delivered by medical devices that lack pediatric safety and efficacy data. Moreover, recent improvements in dialysis technology offered to adult patients are denied to most children. We, in turn, advocate for concerted action by pediatric nephrologists, industry, and health regulatory agencies to increase the development of dedicated HD machines and equipment for children.

First uninterrupted sleep period in children and adolescents with nocturnal enuresis: Added value in diagnosis and follow-up during therapy.

BACKGROUND: The first uninterrupted sleep period (FUSP, time up to the first episode of enuresis/nocturia after falling asleep) is a frequently investigated parameter in adults with nocturia, as it correlates with quality of life. However, it has not been included in pediatric enuresis studies. AIM: Investigate FUSP, circadian renal water and sodium handling, as well as sleep quality before and after desmopressin therapy in enuresis. MATERIALS AND METHODS: We conducted a post hoc analysis of a prospective study in 30 treatment-naïve children with enuresis who underwent a video-polysomnography and a 24-h urine concentration profile before and after 6 months of desmopressin therapy. We analyzed FUSP, periodic limb movements in sleep (PLMS), and arousal indexes and their correlations with the urinary parameters. RESULTS: Sixteen children with a mean age of 10.9 ± 3.1 years had full registrations and were included in this subanalysis. After therapy, FUSP was significantly longer (p < 0.001), and the PLMS index was lower (p = 0.023). Significant differences in the circadian rhythm of diuresis (night/day diuresis, p = 0.041), nocturnal urinary osmolality (p = 0.009), and creatinine (p = 0.001) were found, demonstrating the increase of urinary concentration overnight by desmopressin, as well as a significant antidiuretic effect (diuresis [p = 0.013] and diuresis rate (p = 0.008). There was no correlation between the difference of FUSP, PLMS index, and urinary parameters. Nevertheless, despite this study being underpowered, there are indications of a correlation between nocturnal diuresis and diuresis rate. RESULTS: Our results support the need for further research regarding FUSP in children with enuresis, in accordance with nocturia studies in adults, as this parameter could be valuable in the follow-up and evaluation of therapeutic strategies for enuresis.

European expert recommendations on clinical investigation and evaluation of high-risk medical devices for children.

Several high-risk medical devices for children have become unavailable in the European Union (EU), since requirements and costs for device certification increased markedly due to the EU Medical Device Regulation. The EU-funded CORE-MD project held a workshop in January 2023 with experts from various child health specialties, representatives of European paediatric associations, a regulatory authority and the European Commission Directorate General Health and Food Safety. A virtual follow-up meeting took place in March 2023. We developed recommendations for investigation of high-risk medical devices for children building on participants' expertise and results of a scoping review of clinical trials on high-risk medical devices in children. Approaches for evaluating and certifying high-risk medical devices for market introduction are proposed.

Sodium intake and urinary losses in children on dialysis: a European multicenter prospective study.

BACKGROUND: Sodium (Na) balance is unexplored in dialyzed children. We assessed a simplified sodium balance (sNaB) and its correlates in pediatric patients receiving maintenance dialysis. METHODS: Patients < 18 years old on hemodialysis (HD) or peritoneal dialysis (PD) in six European Pediatric Dialysis Working Group centers were recruited. sNaB was calculated from enteral Na, obtained by a 3-day diet diary, Na intake from medications, and 24-h urinary Na (uNa). Primary outcomes were systolic blood pressure and diastolic blood pressure standard deviation scores (SBP and DBP SDS), obtained by 24-h ambulatory blood pressure monitoring or office BP according to age, and interdialytic weight gain (IDWG). RESULTS: Forty-one patients (31 HD), with a median age of 13.3 (IQR 5.2) years, were enrolled. Twelve patients (29.3%) received Na-containing drugs, accounting for 0.6 (0.7) mEq/kg/day. Median total Na intake was 1.5 (1.1) mEq/kg/day, corresponding to 60.6% of the maximum recommended daily intake for healthy children. Median uNa and sNaB were 0.6 (1.8) mEq/kg/day and 0.9 (1.7) mEq/kg/day, respectively. The strongest independent predictor of sNaB in the cohort was urine output. In patients receiving HD, sNaB correlated with IDWG, pre-HD DBP, and first-hour refill index, a volume index based on blood volume monitoring. sNaB was the strongest predictor of IDWG in multiple regression analysis (ß = 0.63; p = 0.005). Neither SBP SDS nor DBP SDS correlated with sNaB. CONCLUSIONS: Na intake is higher than uNa in children on dialysis, and medications may be an important source of Na. sNaB is best predicted by urine output in the population, and it is a significant independent predictor of IDWG in children on HD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Nutritional management of children with acute kidney injury-clinical practice recommendations from the Pediatric Renal Nutrition Taskforce.

The nutritional management of children with acute kidney injury (AKI) is complex. The dynamic nature of AKI necessitates frequent nutritional assessments and adjustments in management. Dietitians providing medical nutrition therapies to this patient population must consider the interaction of medical treatments and AKI status to effectively support both the nutrition status of patients with AKI as well as limit adverse metabolic derangements associated with inappropriately prescribed nutrition support. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric renal dietitians and pediatric nephrologists, has developed clinical practice recommendations (CPR) for the nutritional management of children with AKI. We address the need for intensive collaboration between dietitians and physicians so that nutritional management is optimized in line with AKI medical treatments. We focus on key challenges faced by dietitians regarding nutrition assessment. Furthermore, we address how nutrition support should be provided to children with AKI while taking into account the effect of various medical treatment modalities of AKI on nutritional needs. Given the poor quality of evidence available, a Delphi survey was conducted to seek consensus from international experts. Statements with a low grade or those that are opinion-based must be carefully considered and adapted to individual patient needs, based on the clinical judgment of the treating physician and dietitian. Research recommendations are provided. CPRs will be regularly audited and updated by the PRNT.

Illness-related parental stress and quality of life in children with kidney diseases.

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.

The efficacy of standard urotherapy in the treatment of nocturnal enuresis in children: A systematic review.

INTRODUCTION: Standard urotherapy in children with nocturnal enuresis (NE) is first-line treatment according to the current International Children's Continence Society (ICCS) guidelines. ICCS defines standard urotherapy as information and demystification, instruction in how to resolve lower urinary tract dysfunction, lifestyle advice, registration of symptoms and voiding habits, and support and encouragement. These interventions often are time consuming and some aspects of urotherapy, such as fluid restrictions, can be a frustrating process for a child, which emphasizes the importance of clarifying their relevance. The purpose of this review is to perform a systematic search in literature to evaluate the use of standard urotherapy in the treatment of children with primary NE (PNE). STUDY DESIGN: A systematic literature search was conducted in MEDLINE, Embase, and CENTRAL based on the key concepts of standard urotherapy and NE. We identified 2,476 studies. After a systematic selection process using the Covidence tool, 39 studies were included. The quality of the studies was assessed by the QualSyst Checklist. Our protocol adheres to the PRISMA statement and was registered in PROSPERO database (CRD42020185611). RESULTS: Most of the 39 included studies scored low in quality. All studies combined several urotherapy interventions and studied different study populations. Twenty-two randomized controlled trials (RCTs) were included, which reported 0-92% of children being dry after urotherapy treatment. Three RCTs, all individualizing and optimizing drinking and voiding during the day and practicing optimal toilet posture, scored higher in quality based on the QualSyst score, and reported few children experiencing complete resolution of NE (5-33%). Eight studies compared the efficacy of urotherapy to a control group, however, conflicting results were found. DISCUSSION: This systematic review presents available literature in the field of standard urotherapy in the treatment of children with PNE. One possible explanation for low efficacy rates of urotherapy in NE is the large heterogeneity of the study populations and interventions. Additionally, the intervention period and the intensity of intervention can have an impact on the outcome. CONCLUSION: The number of clinical studies on standard urotherapy in children with NE is limited and many of them are of poor quality. High quality research in a well-defined NE population is needed to establish the role of standard urotherapy in first-line treatment of children with NE or as an add-on to other first line treatments. We conclude that at present there is insufficient evidence for recommending standard urotherapy to children with PNE as a first line treatment modality.

Clinical characteristics and outcomes of a patient population with atypical hemolytic uremic syndrome and malignant hypertension: analysis from the Global aHUS registry.

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) often caused by alternative complement dysregulation. Patients with aHUS can present with malignant hypertension (MHT), which may also cause TMA. METHODS: This analysis of the Global aHUS Registry (NCT01522183) assessed demographics and clinical characteristics in eculizumab-treated and not-treated patients with aHUS, with (n = 71) and without (n = 1026) malignant hypertension, to further elucidate the potential relationship between aHUS and malignant hypertension. RESULTS: While demographics were similar, patients with aHUS + malignant hypertension had an increased need for renal replacement therapy, including kidney transplantation (47% vs 32%), and more pathogenic variants/anti-complement factor H antibodies (56% vs 37%) than those without malignant hypertension. Not-treated patients with malignant hypertension had the highest incidence of variants/antibodies (65%) and a greater need for kidney transplantation than treated patients with malignant hypertension (65% vs none). In a multivariate analysis, the risk of end-stage kidney disease or death was similar between not-treated patients irrespective of malignant hypertension and was significantly reduced in treated vs not-treated patients with aHUS + malignant hypertension (adjusted HR (95% CI), 0.11 [0.01-0.87], P = 0.036). CONCLUSIONS: These results confirm the high severity and poor prognosis of untreated aHUS and suggest that eculizumab is effective in patients with aHUS ± malignant hypertension. Furthermore, these data highlight the importance of accurate, timely diagnosis and treatment in these populations and support consideration of aHUS in patients with malignant hypertension and TMA. TRIAL REGISTRATION DETAILS: Atypical Hemolytic-Uremic Syndrome (aHUS) Registry. Registry number: NCT01522183 (first listed 31st January, 2012; start date 30th April, 2012).

Reliability of glomerular filtration rate estimating formulas compared to iohexol plasma clearance in critically ill children.

Accurate renal function assessment is crucial to guide intensive care decision-making and drug dosing. Estimates of glomerular filtration rate (eGFR) are routinely used in critically ill children; however, these formulas were never evaluated against measured GFR (mGFR) in this population. We aimed to assess the reliability of common eGFR formulas compared to iohexol plasma clearance (CLiohexol) in a pediatric intensive care (PICU) population. Secondary outcomes were the prevalence of acute kidney injury (AKI) (by pRIFLE criteria) and augmented renal clearance (ARC) (defined as standard GFR for age + 2 standard deviations (SD)) within 48 h after admission based on mGFR and eGFR by the revised Schwartz formula and the difference between these two methods to diagnose AKI and ARC. In children, between 0 and 15 years of age, without chronic renal disease, GFR was measured by CLiohexol and estimated using 26 formulas based on creatinine (Scr), cystatine C (CysC), and betatrace protein (BTP), early after PICU admission. eGFR and mGFR results were compared for the entire study population and in subgroups according to age, using Bland-Altman analysis with calculation of bias, precision, and accuracy expressed as percentage of eGFR results within 30% (P30) and 10% (P10) of mGFR. CLiohexol was measured in 98 patients. Mean CLiohexol (± SD) was 115 ± 54 ml/min/1.73m2. Most eGFR formulas showed overestimation of mGFR with large bias and poor precision reflected by wide limits of agreement (LoA). Bias was larger with CysC- and BTP-based formulas compared to Scr-based formulas. In the entire study population, none of the eGFR formulas showed the minimal desired P30 > 75%. The widely used revised Schwartz formula overestimated mGFR with a high percentage bias of - 18 ± 51% (95% confidence interval (CI) - 29; - 9), poor precision with 95% LoA from - 120 to 84% and insufficient accuracy reflected by P30 of only 51% (95% CI 41; 61), and P10 of 21% (95% CI 13; 66) in the overall population. Although performance of Scr-based formulas was worst in children below 1 month of age, exclusion of neonates and younger children did not result in improved agreement and accuracy. Based on mGFR, prevalence of AKI and ARC within 48 h was 17% and 45% of patients, respectively. There was poor agreement between revised Schwartz formula and mGFR to diagnose AKI (kappa value of 0.342, p < 0.001; sensitivity of 30%, 95% CI 5; 20%) and ARC (kappa value of 0.342, p < 0.001; sensitivity of 70%, 95% CI 33; 58). CONCLUSION: In this proof-of-concept study, eGFR formulas were found to be largely inaccurate in the PICU population. Clinicians should therefore use these formulas with caution to guide drug dosing and therapeutic interventions in critically ill children. More research in subgroup populations is warranted to conclude on generalizability of these study findings. CLINICALTRIALS: gov NCT05179564, registered retrospectively on January 5, 2022. WHAT IS KNOWN: • Both acute kidney injury and augmented renal clearance may be present in PICU patients and warrant adaptation of therapy, including drug dosing. • Biomarker-based eGFR formulas are widely used for GFR assessment in critically ill children, although endogenous filtration biomarkers have important limitations in PICU patients and eGFR formulas have never been validated against measured GFR in this population. WHAT IS NEW: • eGFR formulas were found to be largely inaccurate in the PICU population when compared to measured GFR by iohexol clearance. Clinicians should therefore use these formulas with caution to guide drug dosing and therapeutic interventions in critically ill children. • Iohexol plasma clearance could be considered an alternative for accurate GFR assessment in PICU patients.

Impact of New vs. Old International Children's Continence Society Standardization on the Classification of Treatment Naïve Enuresis Children at Screening: The Value of Voiding Diaries and Questionnaires.

Expert consensus papers recommend differentiating enuresis using questionnaires and voiding diaries into non- (NMNE) and monosymptomatic enuresis (MNE) is crucial at intake to decide the most appropriate workout and treatment. This national, Belgian, prospective study investigates the correlation, consistency, and added value of the two methods, the new against the old International Children's Continence Society (ICCS) definitions, and documents the prevalence of the two enuresis subtypes in our population. Ninety treatment-naïve enuretic children were evaluated with the questionnaire, and the voiding diary and the two clinical management tools were compared. Almost 30% of the children had a different diagnosis with each method, and we observed inconsistencies between them in registering Lower Tract Symptoms (κ = -0.057-0.432 depending on the symptom). Both methods had a high correlation in identifying MNE (rs = 0.612, p = 0.001) but not for NMNE (rs = 0.127, p = 0.248). According to the latest ICCS definitions, the incidence of MNE was significantly lower (7 vs. 48%) with the old standardization. Conclusion: The voiding diary and the questionnaire, as recommended by the ICCS at the screening of treatment-naïve enuretic patients, are considerably inconsistent and have significantly different sensitivities in identifying LUTS and thus differentiating MNE from NMNE. However, the high incidence of LUTS and very low prevalence of MNE suggest that differentiating MNE from NMNE to the maximum might not always correlate with different therapy responses.

Mental Health Outcomes Among Parents of Children With a Chronic Disease During the COVID-19 Pandemic: The Role of Parental Burn-Out.

OBJECTIVE: The COVID-19 pandemic and associated quarantine measures highly impacted parental psychological well-being. Parents of children with chronic diseases might be specifically vulnerable as they already face multiple challenges to provide adequate care for their child. The research questions of the current study were twofold: (a) to examine whether parents of children with a chronic disease experienced more anxiety and depression compared to parents of healthy children and (b) to examine a series of risk factors for worsened well-being (i.e., depression, anxiety, and sleep problems), such as sociodemographic variables, COVID-19-specific variables (i.e., financial worries, living space, and perceived quality of health care), and parental psychological experiences (i.e., parental burn-out and less positive parenting experiences). METHODS: Parents of children with a chronic disease (i.e., the clinical sample; N = 599 and 507 for Research Questions 1 and 2, respectively) and parents of healthy children (i.e., the reference sample: N = 417) filled out an online survey. RESULTS: Findings demonstrated that the parents in the clinical sample reported higher levels of anxiety than parents in the reference sample. Analyses within the clinical sample indicated that COVID-19-specific stressors and parental psychological experiences were associated with higher levels of anxiety, depression, and sleep problems. Mediation analyses furthermore indicated that the association of COVID-19-specific stressors with all outcome measures was mediated by parental burn-out. CONCLUSIONS: Parents of children with a chronic disease constitute a vulnerable group for worse well-being during the current pandemic. Findings suggest interventions directly targeting parental burn-out are warranted.

Assessment and management of obesity and metabolic syndrome in children with CKD stages 2-5 on dialysis and after kidney transplantation-clinical practice recommendations from the Pediatric Renal Nutrition Taskforce.

Obesity and metabolic syndrome (O&MS) due to the worldwide obesity epidemic affects children at all stages of chronic kidney disease (CKD) including dialysis and after kidney transplantation. The presence of O&MS in the pediatric CKD population may augment the already increased cardiovascular risk and contribute to the loss of kidney function. The Pediatric Renal Nutrition Taskforce (PRNT) is an international team of pediatric renal dietitians and pediatric nephrologists who develop clinical practice recommendations (CPRs) for the nutritional management of children with kidney diseases. We present CPRs for the assessment and management of O&MS in children with CKD stages 2-5, on dialysis and after kidney transplantation. We address the risk factors and diagnostic criteria for O&MS and discuss their management focusing on non-pharmacological treatment management, including diet, physical activity, and behavior modification in the context of age and CKD stage. The statements have been graded using the American Academy of Pediatrics grading matrix. Statements with a low grade or those that are opinion-based must be carefully considered and adapted to individual patient needs based on the clinical judgment of the treating physician and dietitian. Research recommendations are provided. The CPRs will be periodically audited and updated by the PRNT.

Influenza and pneumococcus vaccination rates in pediatric dialysis patients in Europe: recommendations vs reality A European Pediatric Dialysis Working Group and European Society for Pediatric Nephrology Dialysis Working Group study

Background/aim: Children on dialysis are under increased risk of influenza and invasive pneumococcal disease. Although vaccination against these microorganisms are recommended in dialysis patients and despite the fact that these vaccines can reduce disease burden and rates of hospitalization due to infection, vaccination rates are below expected and desired. We aimed to evaluate influenza and pneumococcal vaccination and infection rates in European pediatric dialysis centers. Materials and methods: In 16 centers from 11 countries, 357 pediatric dialysis patients were evaluated retrospectively during 1 year of observation period between 01.01.2014 and 01.01.2015. Results: In all centers, vaccination policy included immunization of dialysis patients with inactive influenza vaccine and pneumococcal conjugate vaccine (PCV). Fifty percent of the centers recommended pneumococcal polysaccharide vaccine following routine PCV series. A significantly higher pneumococcal vaccination rate (43.9%) was seen in peritoneal dialysis (PD) patients compared to those on hemodialysis (HD) (32.9%) (p = 0.035), while the rates for influenza were similar (42.4% and 46.1% respectively, p = 0.496). Among all dialysis patients, 2.2% (n = 8) developed pneumonia and 6.4% (n = 23) was infected by Influenza. Pneumococcic pneumonia rate was 5% for 140 patients who received antipneumococcal vaccine, while only one pneumonia episode was recorded out of 217 unvaccinated patients (p = 0.007). The influenza virus infection rates were similar for patients vaccinated and nonvaccinated (7 % and 6 %, respectively). Conclusions: Although influenza and pneumococcal vaccines are highly recommended in pediatric dialysis patients, vaccination rates were lower than expected. Pneumococcal vaccination rates were higher in PD compared to the patients on HD. The rate of children with influenza infection was higher than pneumonia. The efficacy of influenza and pneumococcal vaccines was highlighted by the low infection rates. Higher pneumonia rates in patients vaccinated against pneumococcus compared to unvaccinated ones might be due to coexisting risk factors.