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Background: Nephropathic cystinosis (NC) is a rare lysosomal disease, leading to early kidney failure and extra-renal comorbidities. Its prognosis strongly relies on early diagnosis and treatment by cysteamine. Developing economies (DEing) face many challenges when treating patients for rare and chronic diseases. The aim here is to evaluate the access to investigations and treatment in DEing, and to assess for potential inequalities with Developed Economies (DEed). Methods: In this international cross-sectional study, a questionnaire on access, price and reimbursement of genetic, biological analyses, and treatment was sent to nephrology centers worldwide during 2022. Results: A total of 109 centers responded, coming from 49 countries and managing 741 patients: 43 centers from 30 DEing and Economies in transition (TrE), and 66 from 19 DEed. In 2022, genetics availability was 63% in DEing and 100% in DEed, whereas intra leukocytes cystine levels (IL-CL) were available for 30% of DEing patients, and 94% of DEed patients, both increasing over the last decade, as has access to immediate release cysteamine and to cysteamine eye drops in DEing. However, delayed released cysteamine can be delivered to only 7% vs. 74% of patients from DEing and DEed, respectively, and is still poorly reimbursed in DEing. Conclusions: Over the last decade, access to investigations (namely genetics and IL-CL) and to cysteamine have improved in DEing and TrE. However, discrepancies remain with DEed: access to delayed released cysteamine is limited, and reimbursement is still profoundly insufficient, therefore limiting their current use. [ABSTRACT FROM AUTHOR]

The article focuses on pediatric nephrologists' perception and knowledge of evidence-based guideline development methodology. Topics discussed include the importance of guidelines in clinical practice, physicians' reliance on different guidance documents, and the need for improved understanding of Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology among pediatric nephrologists.

Background: This retrospective real-world study used data from two registries, International Pediatric Peritoneal Dialysis Network (IPPN) and International Pediatric Hemodialysis Network (IPHN), to characterize the efficacy and safety of continuous erythropoietin receptor activator (C.E.R.A.) in pediatric patients with chronic kidney disease (CKD) on peritoneal dialysis (PD) or hemodialysis (HD). Methods: IPPN and IPHN collect prospective data (baseline and every 6 months) from pediatric PD and HD centers worldwide. Demographics, clinical characteristics, dialysis information, treatment, laboratory parameters, number and causes of hospitalization events, and deaths were extracted for patients on C.E.R.A. treatment (IPPN: 2007–2021; IPHN: 2013–2021). Results: We analyzed 177 patients on PD (median age 10.6 years) and 52 patients on HD (median age 14.1 years) who had ≥ 1 observation while being treated with C.E.R.A. The median (interquartile range [IQR]) observation time under C.E.R.A. exposure was 6 (0–12.5) and 12 (0–18) months, respectively. Hemoglobin concentrations were stable over time; respective means (standard deviation) at last observation were 10.9 (1.7) g/dL and 10.4 (1.7) g/dL. Respective median (IQR) monthly C.E.R.A. doses at last observation were 3.5 (2.3–5.1) µg/kg, or 95 (62–145) µg/m2 and 2.1 (1.2–3.4) µg/kg, or 63 (40–98) µg/m2. Non-elective hospitalizations occurred in 102 (58%) PD and 32 (62%) HD patients. Seven deaths occurred (19.8 deaths per 1000 observation years). Conclusions: C.E.R.A. was associated with efficient maintenance of hemoglobin concentrations in pediatric patients with CKD on dialysis, and appeared to have a favorable safety profile. The current analysis revealed no safety signals. [ABSTRACT FROM AUTHOR]

Background : The guidelines for training of patients and caregivers to perform home peritoneal dialysis (PD) uniformly include recommendations pertaining to the prevention of peritonitis. The objective of this study conducted by the International Pediatric Peritoneal Dialysis Network (IPPN) was to investigate the training practices for pediatric PD and to evaluate the impact of these practices on the peritonitis and exit-site infection (ESI) rate. Methods: A questionnaire regarding details of the PD program and training practices was distributed to IPPN member centers, while peritonitis and ESI rates were either derived from the IPPN registry or obtained directly from the centers. Poisson univariate and multivariate regression was used to determine the training-related peritonitis and ESI risk factors. Results: Sixty-two of 137 centers responded. Information on peritonitis and ESI rates were available from fifty centers. Training was conducted by a PD nurse in 93.5% of centers, most commonly (50%) as an in-hospital program. The median total training time was 24 hours, with a formal assessment conducted in 88.7% and skills demonstration in 71% of centers. Home visits were performed by 58% of centers. Shorter (< 20 hours) training duration and lower number of training tools (both p < 0.02) were associated with higher peritonitis rate, after adjustment for proportion of treated infants and income of country of residence. Conclusions: An association between training duration and the number of training tools represent potentially modifiable risk factors to reduce peritonitis rates within the pediatric PD population. [ABSTRACT FROM AUTHOR]

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Background and objectives: Dialysis disequilibrium syndrome (DDS) is a rare neurological complication, most commonly affecting patients undergoing new initiation of hemodialysis (HD), but can also be seen in patients receiving chronic dialysis who miss regular treatments, patients having acute kidney injury (AKI), and in those treated with continuous kidney replacement therapy (CKRT) or peritoneal dialysis (PD). Although the pathogenesis is not well understood, DDS is likely a result of multiple physiological abnormalities. In this systematic review, we provide a synopsis of the data available on DDS that allow for a clear picture of its pathogenesis, preventive measures, and focus on effective management strategies. Methods: We conducted a literature search on PubMed/Medline and Embase from January 1960 to January 2021. Studies were included if the patient developed DDS irrespective of age and gender. A summary table was used to summarize the data from individual studies and included study type, population group, age group, sample size, patient characteristics, blood and dialysate flow rate, and overall outcome. A descriptive analysis calculating the frequency of population size, symptoms, and various treatments was performed using R software version 3.1.0. Results: A total of 49 studies (321 samples) were identified and analyzed. Out of the included 49 studies, a total of 48 studies reported the presence of DSS among patients (1 study reported based on number of dialysis and therefore was not considered for analysis). Among these 48 studies, 74.3% (226/304) patients were reported to have DSS. The most common symptoms were nausea (25.2%), headache (24.8%), vomiting (23.9%), muscle cramps (18.1%), affected level of consciousness (8.8%), confusion (4.4%), and seizure (4.9%) among the 226 DDS patients. Furthermore, 12 studies decided to switch from HD to alternative dialysis modalities including continuous venovenous hemofiltration/hemodiafiltration (CVVH/CVVHDF) or PD which reported no DDS symptoms. Conclusion: Early recognition and timely prevention are crucial for DDS patients. We have provided comprehensive clinical practice points for pediatric, adolescent, and young adult populations. However, it is essential to recognize that DDS was reported more frequently in the early dialysis era, as there was a lack of advanced dialysis technology and limited resources. [ABSTRACT FROM AUTHOR]

Background: Autosomal recessive polycystic kidney disease (ARPKD) is a rare severe hepatorenal disease. Survivors of pulmonary hypoplasia and patients with milder presentations often achieve long-term survival but frequently require kidney and/or liver transplantation. Objective: To examine the use of clinical, surrogate and patient-centered outcomes in studies on ARPKD with special attention to core outcomes of the Standardized Outcomes in NephroloGy project for children with chronic kidney disease (SONG-Kids). Data sources and study eligibility criteria: A systematic MEDLINE literature search identified 367 ARPKD studies published since 1990; however, of these 134 were excluded because they did not report any clinical outcomes (e.g. only histopathological, genetic, protein structure or radiological markers), 19 studies because they only included prenatal patients and 138 because they were case reports with ≤ 3 patients. Study appraisal: Seventy-six eligible studies were examined for study type, size, intervention, and reported outcomes by organ system and type, including all SONG-kids tier 1–3 outcomes. Participants: There were 3231 patient-reports of children and adults with ARPKD. Results: The overwhelming majority of studies reported clinical and surrogate outcomes (75/76 (98%) and 73/76 (96%)), but only 11/76 (14%) examined patient-centered outcomes and only 2/76 (3%) used validated instruments to capture them. Of the SONG-Kids core outcomes, kidney function was reported almost universally (70/76 (92%), infection and survival in three quarters (57/76 (75%), 55/76 (72%)) and measures of life participation (including neurological impairment) only rarely and inconsistently (16/76 (21%)). Limitations: Thirty studies (39%) were of low quality as they were either narrative case reports (n = 14, 18%) and/or patients with ARPKD were an indistinguishable subgroup (n = 18, 24%). Only 28 trials compared interventions, but none were randomized. Conclusions and implications: Studies that reported clinical outcomes in ARPKD usually covered the core outcome domains of kidney function, infections, and survival, but measures of life participation and patient-centered outcomes are distinctly lacking and require more attention in future trials. [ABSTRACT FROM AUTHOR]

Background: The kidney is central for maintaining water balance. As a corollary, patients with impaired kidney function are prone to pathological fluid volumes. Total body water (TBW) is distributed between the extracellular (ECW) and intracellular fluid compartments (ICW). In clinical practice, the judgment of hydration status does not allow to distinguish between ECW and ICW. Here, we evaluate the hydration status in children with chronic kidney disease by analyzing TBW, ECW, and ICW. Methods: Hydration was quantified using whole-body bioimpedance spectroscopy (BCM) in 128 outpatients (1–25 years, 52 girls). Forty-two were transplanted (TPL), 43 suffered from chronic kidney disease without kidney replacement therapy (CKD), 21 were on peritoneal dialysis (PD), and 22 on hemodialysis (HD). HD patients were investigated before, after, and sequentially during dialysis. Results: The ECW and ICW values obtained by BCM were of the same magnitude as those from the literature using isotope dilution. When compared with a healthy control group, TBW was increased in 9 TPL, 9 CKD, 1 PD, and 11 HD patients before but in none after dialysis. The decline of overhydration during dialysis (p < 0.001, n = 22) correlated with the change in body weight (R2 = 0.62). The kinetics of fluid compartment changes assessed twice in six HD patients revealed a reproducible linear decay of the ECW/ICW ratio due to an increase of ICW and a decrease of ECW. Conclusion: BCM quantifies TBW and acute changes of ECW and ICW in children with chronic kidney failure. The clinical utility of measuring TBW, ECW, and ICW should be defined in the future. [ABSTRACT FROM AUTHOR]

Changes in arterial structure and function are seen early in the course of chronic kidney disease (CKD) and have been causally associated with cardiovascular (CV) morbidity. Numerous potential injuries encompassing both traditional and uremia-specific CV risk factors can induce structural arterial changes and accelerate arterial stiffening. When the buffering capacity of the normally elastic arteries is reduced, damage to vulnerable microcirculatory beds can occur. Moreover, the resultant increase to cardiac afterload contributes to the development of left ventricular hypertrophy and cardiac dysfunction. Adult studies have linked arterial stiffness with increased risk of mortality, CV events, cognitive decline, and CKD progression. Pulse wave velocity (PWV) is currently the gold standard of arterial stiffness assessment but its measurement in children is challenging due to technical difficulties and physiologic aspects related to growth and poor standardization between algorithms for calculating PWV. Nevertheless, studies in pediatric CKD have reported increased arterial stiffness in children with advanced CKD, on dialysis, and after kidney transplantation. Development of arterial stiffness in children with CKD is closely related to mineral-bone disease and hypertension, but other factors may also play a significant role. The clinical relevance of accelerated arterial stiffness in childhood on cardiovascular outcomes in adult life remains unclear, and prospective studies are needed. In this review we discuss mechanisms leading to arterial stiffness in CKD and its clinical implications, along with issues surrounding the technical aspects of arterial stiffness assessment in children. [ABSTRACT FROM AUTHOR]

National and international registries have great potential for providing data that describe disease burden, treatments, and outcomes especially in rare diseases. In the setting of pediatric end-stage renal disease (ESRD), the available data are limited to highly developed countries, whereas the lack of data from emerging economies blurs the global perspective. In order to improve the pediatric dialysis care worldwide, provide global benchmarking of pediatric dialysis outcome, and assign useful tools and management algorithms based on evidence-based medicine, the International Pediatric Peritoneal Dialysis Network (IPPN) was established in 2007. In recent years, the Registry has provided comprehensive data on relevant clinical issues in pediatric peritoneal dialysis patients including nutritional status, growth, cardiovascular disease, anemia management, mineral and bone disorders, preservation of residual kidney function, access-related complications, and impact of associated comorbidities. A unique feature of the registry is the ability to compare practices and outcomes between countries and world regions. In the current review, we describe study design and collection methods, summarize the core IPPN findings based on its 12-year experience and 13 publications, and discuss the future perspective. [ABSTRACT FROM AUTHOR]

Congenital nephrotic syndrome (CNS) is a heterogeneous group of disorders characterized by nephrotic-range proteinuria, hypoalbuminaemia and oedema, which manifest in utero or during the first 3 months of life. The main cause of CNS is genetic defects in podocytes; however, it can also be caused, in rare cases, by congenital infections or maternal allo-immune disease. Management of CNS is very challenging because patients are prone to severe complications, such as haemodynamic compromise, infections, thromboses, impaired growth and kidney failure. In this consensus statement, experts from the European Reference Network for Kidney Diseases (ERKNet) and the European Society for Paediatric Nephrology (ESPN) summarize the current evidence and present recommendations for the management of CNS, including the use of renin-angiotensin system inhibitors, diuretics, anticoagulation and infection prophylaxis. Therapeutic management should be adapted to the clinical severity of the condition with the aim of maintaining intravascular euvolaemia and adequate nutrition, while preventing complications and preserving central and peripheral vessels. We do not recommend performing routine early nephrectomies but suggest that they are considered in patients with severe complications despite optimal conservative treatment, and before transplantation in patients with persisting nephrotic syndrome and/or a WT1-dominant pathogenic variant. [ABSTRACT FROM AUTHOR]

European Reference Networks (ERNs) were founded on the principle that many rare disease (RD) issues are pan-European and any single Member State cannot solve them alone. In 2021, ERNs are already in the deployment stage; however, their day-to-day functioning and realization of their potential are still severely hampered by many challenges, including issues in governance and regulation, lack of legal status, insufficient and unsustainable funding, lack of ERN integration into national systems, endangered collaboration with UK RD experts due to Brexit, insufficient exploitation of ERN potential in RD research, underappreciation of highly qualified human resources, problems with the involvement of patient representatives, and still unclear place of ERNs in the overall European RD and digital ecosystem. Bold and innovative solutions that must be taken to solve these challenges inevitably involve pan-European collaboration across several sectors and among multistakeholder RD communities and in many cases crucially rely on the constructive dialogue and coherent, united decisions of national and European authorities that are based on common EU values. Importantly, unresolved challenges may have a strong impact on the further sustainability of ERNs and their ability to realize full potential in addressing huge unmet needs of RD patients and their families. [ABSTRACT FROM AUTHOR]

Background: The International Pediatric Nephrology Association (IPNA) Global Kidney Replacement Therapy (KRT) Registry was established to evaluate the incidence and outcomes of kidney replacement therapy (dialysis and transplantation) provided to children worldwide. Analysis of registry data for separate regions is feasible. Methods: Three centers located in Shanghai, Guangzhou, and Zhengzhou, which have the greatest number of pediatric kidney transplantation cases in China, participated in this analysis of transplant data. Data were registered by each center for patients under the age of 19 years who received a single-organ kidney transplant for the first time between 2011 and 2018. Results: In total, 415 patients (59.8% male) aged 1.4–18.7 (median 12.1) years were followed for 0.3–97.1 (median 27.7) months. The number of kidney transplants increased from a total of 129 during 2011–2014 to 286 cases during 2015–2018. 85.8% of patients received the transplanted kidney from a pediatric (age < 19 years) donor, and deceased donors accounted for 94% of all donors. 8.0% of grafts were lost. One and 5-year patient survival rates were 97.6% and 95.5%, respectively. The major cause of death was infection (7/14). Similar graft and patient survival rates were observed for organs from pediatric and adult donors in 6–11 and 12–18 year recipient age groups, whereas recipients < 6 years showed inferior patient and graft survival. Conclusions: Pediatric kidney transplantation shows favorable short-term and medium-term outcomes in China. Our experience supports use of pediatric donors in pediatric kidney transplantation, but attention directed to the outcome of recipients aged under 6 is necessary. [ABSTRACT FROM AUTHOR]

Background: Secondary hyperparathyroidism (sHPT), a complication of chronic kidney disease (CKD) characterized by persistently elevated parathyroid hormone (PTH), alterations in calcium-phosphorus homeostasis, and vitamin D metabolism, affects 50% of children receiving dialysis. A significant proportion of these children develop CKD-mineral and bone disorder (CKD-MBD), associated with an increased risk of fractures and vascular calcification. The standard of care for sHPT in children includes vitamin D sterols, calcium supplementation, and phosphate binders. Several agents are approved for sHPT treatment in adults undergoing dialysis, including vitamin D analogs and calcimimetics, with limited information on their safety and efficacy in children. The calcimimetic cinacalcet is approved for use in adults with sHPT on dialysis, but is not approved for pediatric use outside Europe. Methods: This review provides dosing, safety, and efficacy information from Amgen-sponsored cinacalcet pediatric trials and data from non-Amgen sponsored clinical studies. Results: The Amgen cinacalcet pediatric clinical development program consisted of two Phase 3 randomized studies, one Phase 3 single arm extension study, one open-label Phase 2 study, and two open-label Phase 1 studies. Effects of cinacalcet on PTH varied across studies. Overall, 7.4 to 57.1% of subjects who received cinacalcet in an Amgen clinical trial attained PTH levels within recommended target ranges and 22.2 to 70.6% observed a ≥ 30% reduction in PTH. In addition, significant reductions in PTH were demonstrated in all non-Amgen-supported studies. Conclusions: To help inform the pediatric nephrology community, this manuscript contains the most comprehensive review of cinacalcet usage in pediatric CKD patients to date. [ABSTRACT FROM AUTHOR]

Idiopathic nephrotic syndrome newly affects 1–3 per 100,000 children per year. Approximately 85% of cases show complete remission of proteinuria following glucocorticoid treatment. Patients who do not achieve complete remission within 4–6 weeks of glucocorticoid treatment have steroid-resistant nephrotic syndrome (SRNS). In 10–30% of steroid-resistant patients, mutations in podocyte-associated genes can be detected, whereas an undefined circulating factor of immune origin is assumed in the remaining ones. Diagnosis and management of SRNS is a great challenge due to its heterogeneous etiology, frequent lack of remission by further immunosuppressive treatment, and severe complications including the development of end-stage kidney disease and recurrence after renal transplantation. A team of experts including pediatric nephrologists and renal geneticists from the International Pediatric Nephrology Association (IPNA), a renal pathologist, and an adult nephrologist have now developed comprehensive clinical practice recommendations on the diagnosis and management of SRNS in children. The team performed a systematic literature review on 9 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, formulated recommendations and formally graded them at a consensus meeting, with input from patient representatives and a dietician acting as external advisors and a voting panel of pediatric nephrologists. Research recommendations are also given. [ABSTRACT FROM AUTHOR]

Background: Prenatal ethanol exposure has been shown to reduce nephron endowment in animal models, but the effect of alcohol during human pregnancy on postnatal kidney function has not been explored. We aim to investigate the potential association of maternal alcohol consumption during pregnancy with the offspring renal function, considering potential confounding by intrauterine growth and children's current nutritional status. Methods: Prospective longitudinal study in a random sample of 1093 children from a population-based birth cohort. Anthropometrics and estimated glomerular filtration rate (eGFR) were assessed at 7 years of age. Multiple linear regression models were fitted, adjusting for child's gender, age, birthweight, and maternal age, education, prepregnancy nutritional status, and smoking. Results: Thirteen percent of mothers consumed alcohol during pregnancy. At 7 years of age, eGFR was significantly lower in children with prenatal alcohol exposure (134 ± 17 vs.138 ± 16 mL/min/1.73m2, p = 0.014). The effect was dose dependent and only present in overweight and obese children, among whom adjusted eGFR was −6.6(−12.0 to −1.1)mL/min/1.73m2 and −11.1(−21.3 to −1.2)mL/min/1.73m2 in those exposed to ≤ 40 g and to > 40 g of alcohol per week, respectively, compared to no consumption (ptrend = 0.002). Conclusions: Prenatal alcohol exposure has a dose-dependent adverse effect on renal function at school age in overweight and obese children. [ABSTRACT FROM AUTHOR]

It is unknown whether early diagnosis of autosomal dominant polycystic kidney disease (ADPKD) can enable earlier management and improve outcomes. We conducted a post hoc analysis of data from the TEMPO 3:4 trial. Subjects were stratified by ADPKD diagnosis at age ≤18 (childhood diagnosis [CD]) or>18 (adulthood diagnosis [AD]). Groups were compared for baseline characteristics and total kidney volume (TKV) growth and estimated glomerular filtration rate (eGFR) decline over 3 years. 294 CD and 1148 AD subjects were analyzed. At inclusion, CD subjects were younger (mean age 34.2 versus 39.8 years; p < 0.0001) and had better eGFR (mean ± SD 87.4 ± 23.9 versus 80.1 ± 20.7 mL/min/1.73 m2; p < 0.0001), while CD had more severe Mayo risk classification (p < 0.0001) and more PKD1 mutations (p = 0.003). No statistical differences were found in TKV or eGFR change. At study end, placebo-treated CD subjects had better eGFR than projected by a prediction equation (mean difference ±SD for observed versus predicted eGFR: 2.18 ± 10.7 mL/min/1.73 m2; p = 0.0475). However, these results are not confirmed when excluding stage 1 CKD. Whether CD subjects, despite their risk profile, have a slower disease course than predicted remains inconclusive. Future studies are needed to confirm that early diagnosis and management can alter the disease course of ADPKD. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is a life-limiting comorbidity in patients with chronic kidney disease (CKD). In childhood, imaging studies have demonstrated early phenotypic characteristics including increases in left ventricular mass, carotid artery intima-media thickness, and pulse wave velocity, which occur even in young children with early stages of CKD. Vascular calcifications are the signature of an advanced phenotype and are mainly found in adolescents and young adults treated with dialysis. Association studies have provided valuable information regarding the significance of a multitude of risk factors in promoting CVD in children with CKD by using intermediate endpoints of measurements of surrogate parameters of CVD. Dialysis aggravates pre-existing risk factors and accelerates the progression of CVD with additional dialysis-related risk factors. Coronary artery calcifications in children and young adults with CKD accumulate in a time-dependent manner on dialysis. Identification of risk factors has led to improved understanding of principal mechanisms of CKD-induced damage to the cardiovascular system. Treatment strategies include assessment and monitoring of individual risk factor load, optimization of treatment of modifiable risk factors, and intensified hemodialysis if early transplantation is not possible. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate outcome of children on chronic peritoneal dialysis (PD) with a concurrent colostomy. Methods: Patients were identified through the International Pediatric Peritoneal Dialysis Network (IPPN) registry. Matched controls were randomly selected from the registry. Data were collected through the IPPN database and a survey disseminated to all participating sites. Results: Fifteen centers reported 20 children who received chronic PD with a co-existing colostomy. The most common cause of end stage kidney disease was congenital anomalies of the kidney and urinary tract (n = 16, 80%). The main reason for colostomy placement was anorectal malformation (n = 13, 65%). The median age at colostomy creation and PD catheter (PDC) insertion were 0.1 (IQR, 0–2.2) and 2.8 (IQR 0.2–18.8) months, respectively. The colostomies and PDCs were present together for a median 18 (IQR, 4.9–35.8) months. The median age at PDC placement in 46 controls was 3.4 (IQR, 0.2–7.4) months of age. Fourteen patients (70%) developed 39 episodes of peritonitis. The annualized peritonitis rate was significantly higher in the colostomy group (1.13 vs. 0.70 episodes per patient year; p = 0.02). Predominant causative microorganisms were Staphylococcus aureus (15%) and Pseudomonas aeruginosa (13%). There were 12 exit site infection (ESI) episodes reported exclusively in colostomy patients. Seven colostomy children (35%) died during their course of PD, in two cases due to peritonitis. Conclusion: Although feasible in children with a colostomy, chronic PD is associated with an increased risk of peritonitis and mortality. Continued efforts to reduce infection risk for this complex patient population are essential. [ABSTRACT FROM AUTHOR]

This report describes the rationale and design of a study assessing tolvaptan in children with autosomal dominant polycystic kidney disease (ADPKD). Phase A is a 1-year, randomized, double-blind, placebo-controlled, multicenter trial. Phase B is a 2-year, open-label extension. The target population is at least 60 children aged 12-17 years, diagnosed by family history and/or genetic criteria and the presence of ≥ 10 renal cysts, each ≥ 0.5 cm on magnetic resonance imaging. Subjects will be allocated into 4 groups: females 15-17 years; females 12-14 years; males 15-17 years; and males 12-14 years. Up to 40 subjects aged 4-11 years may also enroll, provided they meet the entry criteria. Weight-adjusted tolvaptan doses, titrated once to achieve a tolerated maintenance dose, and matching placebo will be administered twice-daily. Assessments include spot urine osmolality and specific gravity (co-primary endpoints), height-adjusted total kidney volume, estimated glomerular filtration rate, pharmacodynamic parameters (urine volume, fluid intake and fluid balance, serum sodium, serum creatinine, free water clearance), pharmacokinetic parameters, safety (aquaretic adverse events, changes from baseline in creatinine, vital signs, laboratory values including liver function tests), and generic pediatric quality of life assessments.Conclusion: This will be the first clinical study to evaluate tolvaptan in pediatric ADPKD. What is Known: • Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder causing the development of cysts that impede kidney function over time and eventually induce renal failure • There are few data on the effects of tolvaptan, the only treatment approved for adults to slow disease progression, in pediatric ADPKD patients with early-stage disease What is New: • A phase 3, placebo-controlled study is evaluating tolvaptan over 3 years in children and adolescents with ADPKD • This study is designed to account for challenges of tolvaptan dosing and outcome assessment specific to the pediatric population. [ABSTRACT FROM AUTHOR]

Intradialytic hypotension (IDH) is a common adverse event resulting in premature interruption of hemodialysis, and consequently, inadequate fluid and solute removal. IDH occurs in response to the reduction in blood volume during ultrafiltration and subsequent poor compensatory mechanisms due to abnormal cardiac function or autonomic or baroreceptor failure. Pediatric patients are inherently at risk for IDH due to the added difficulty of determining and attaining an accurate dry weight. While frequent blood pressure monitoring, dialysate sodium profiling, ultrafiltration-guided blood volume monitoring, dialysate cooling, hemodiafiltration, and intradialytic mannitol and midodrine have been used to prevent IDH, they have not been extensively studied in pediatric population. Lack of large-scale studies on IDH in children makes it difficult to develop evidence-based management guidelines. Here, we aim to review IDH preventative strategies in the pediatric population and outlay recommendations from the Pediatric Continuous Renal Replacement Therapy (PCRRT) Workgroup. Without strong evidence in the literature, our recommendations from the expert panel reflect expert opinion and serve as a valuable guide. [ABSTRACT FROM AUTHOR]

Background: Current guidelines advocate use of arteriovenous fistula (AVF) over central venous catheter (CVC) for children starting hemodialysis (HD). European data on current practice, determinants of access choice and switches, patient survival, and access to transplantation are limited.Methods: We included incident patients from 18 European countries who started HD from 2000 to 2013 for whom vascular access type was reported to the ESPN/ERA-EDTA Registry. Data were evaluated using descriptive statistics, logistic and Cox regression models, and cumulative incidence competing risk analysis.Results: Three hundred ninety-three (55.1%) of 713 children started HD with a CVC and were more often females, younger, had more often an unknown diagnosis, glomerulonephritis, or vasculitis, and lower hemoglobin and height-SDS at HD initiation. AVF patients were 91% less likely to switch to a second access, and two-year patient survival was 99.6% (CVC, 97.2%). Children who started with an AVF were less likely to receive a living donor transplant (adjusted HR, 0.30; 95% CI, 0.16-0.54) and more likely to receive a deceased donor transplant (adjusted HR, 1.50; 95% CI, 1.17-1.93), even after excluding patients who died or were transplanted in the first 6 months.Conclusions: CVC remains the most frequent type of vascular access in European children commencing HD. Our results suggest that the choice for CVC is influenced by the time of referral, rapid onset of end-stage renal disease, young age, and an expected short time to transplantation. The role of vascular access type on the pattern between living and deceased donation in subsequent transplantation requires further study. [ABSTRACT FROM AUTHOR]

Background: This randomized phase 3 study evaluated the efficacy and safety of cinacalcet in children with secondary hyperparathyroidism (SHPT) receiving dialysis.Methods: This study had double-blind and open-label phases. Eligible patients aged 6-< 18 years were randomized to cinacalcet (starting dose ≤ 0.20 mg/kg) or placebo. The primary endpoint was ≥ 30% reduction from baseline in mean intact parathyroid hormone (iPTH). Secondary endpoints included mean iPTH ≤ 300 pg/mL; percentage change from baseline in corrected total serum calcium, phosphorus, and calcium phosphorus product (Ca × P); and safety.Results: The double-blind phase comprised 43 patients (cinacalcet, n = 22; placebo, n = 21). Nineteen months into the study, regulatory authorities were notified of a fatality; the study was subsequently terminated after a 14-month clinical hold. Before the hold, 12 patients (55%) on cinacalcet and four (19%) on placebo achieved the primary endpoint (p = 0.017), and 27% and 24%, respectively, achieved iPTH ≤ 300 pg/mL. The between-group differences (95% CI) in percentage changes for total serum calcium, phosphorus, and Ca × P were − 4% (− 9 to 1%), − 6% (− 21 to 8%), and − 10% (− 23 to 3%). The mean maximum actual weight-adjusted daily cinacalcet dosage administered was 0.99 mg/kg/day. Overall, 82% of patients on cinacalcet and 86% on placebo had ≥ 1 treatment-emergent adverse event; the most common were vomiting (32%, 24%, respectively), hypocalcemia (23%, 19%), nausea (18%, 14%), and hypertension (14%, 24%).Conclusions: Despite early termination, efficacy and safety outcomes observed with cinacalcet in children with SHPT on dialysis were consistent with adult observations, suggesting cinacalcet may meet an unmet medical need for this population. [ABSTRACT FROM AUTHOR]

Background: Bioimpedance spectroscopy (BIS) with a whole-body model to distinguish excess fluid from major body tissue hydration can provide objective assessment of fluid status. BIS is integrated into the Body Composition Monitor (BCM) and is validated in adults, but not children. This study aimed to (1) assess agreement between BCM-measured total body water (TBW) and a gold standard technique in healthy children, (2) compare TBW_BCM with TBW from Urea Kinetic Modelling (UKM) in haemodialysis children and (3) investigate systematic deviation from zero in measured excess fluid in healthy children across paediatric age range.Methods: TBW_BCM and excess fluid was determined from standard wrist-to-ankle BCM measurement. TBW_D2O was determined from deuterium concentration decline in serial urine samples over 5 days in healthy children. UKM was used to measure body water in children receiving haemodialysis. Agreement between methods was analysed using paired t test and Bland-Altman method comparison.Results: In 61 healthy children (6-14 years, 32 male), mean TBW_BCM and TBW_D2O were 21.1 ± 5.6 and 20.5 ± 5.8 L respectively. There was good agreement between TBW_BCM and TBW_D2O (R2 = 0.97). In six haemodialysis children (4-13 years, 4 male), 45 concomitant measurements over 8 months showed good TBW_BCM and TBW_UKM agreement (mean difference − 0.4 L, 2SD = ± 3.0 L). In 634 healthy children (2-17 years, 300 male), BCM-measured overhydration was − 0.1 ± 0.7 L (10-90th percentile − 0.8 to + 0.6 L). There was no correlation between age and OH (p = 0.28).Conclusions: These results suggest BCM can be used in children as young as 2 years to measure normally hydrated weight and assess fluid status. [ABSTRACT FROM AUTHOR]

Background: To describe the factors affecting the incidence of renal replacement therapy (RRT) among children, information from RRT registries is required. We aimed to give an overview of existing pediatric RRT registries worldwide, identify regions with a need to commence or increase data collection on pediatric RRT, and provide a rationale for developing a global RRT registry.Methods: A survey assessing pediatric RRT registry status was sent to International Pediatric Nephrology Associateion (IPNA) members in 127 countries in January 2016. The survey was complemented by a systematic literature search for active pediatric RRT registries.Results: Complete survey responses were retrieved from 94 countries (representing 86.2% of the world childhood population), with 84 (81.2%) having the means to provide RRT to children, given that there are no other limitations such as financial, social, or religious restraints. Fifty-one (35.3%) countries had national registries for both dialysis and transplantation, nine (30.0%) either had a dialysis or a transplant registry, six participated in international registries only (2.7%), and in 18 (13.2%), children on RRT were not followed in any registry. The search identified 92 pediatric RRT registries, primarily national registries located in Europe, North America, and Asia.Conclusions: Although pediatric RRT can be provided in 84 countries representing 81.2% of the world’s childhood population, national pediatric RRT registries are unavailable in many countries. To improve knowledge about the incidence and outcomes of pediatric RRT around the globe, an international population-based pediatric RRT registry has recently been initiated. [ABSTRACT FROM AUTHOR]

Background: As outcome data for prune belly syndrome (PBS) complicated by end-stage renal disease are scarce, we analyzed characteristics and outcomes of children with PBS using the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry data. Methods: Data were available for 88 male PBS patients aged <20 years who started renal replacement therapy (RRT) between 1990 and 2013 in 35 European countries. Patient characteristics, survival, and transplantation outcomes were compared with those of male patients requiring RRT due to congenital obstructive uropathy (COU) and renal hypoplasia or dysplasia (RHD). Results: Median age at onset of RRT in PBS was lower [7.0; interquartile range (IQR) 0.9-12.2 years] than in COU (9.6; IQR: 3.0-14.1 years) and RHD (9.4; IQR: 2.7-14.2 years). Unadjusted 10-year patient survival was 85% for PBS, 94% for COU, and 91% for RHD. After adjustment for country, period, and age, PBS mortality was similar to that of RHD but higher compared with COU [hazard ratio (HR) 1.96, 95% confidence interval (CI) 1.03-3.74]. Seventy-four PBS patients (84%) received a first kidney transplant after a median time on dialysis of 8.4 (IQR 0.0-21.1) months. Outcomes with respect to time on dialysis before transplantation, chance of receiving a first transplant within 2 years after commencing RRT, and death-censored, adjusted risk of graft loss were similar for all groups. Conclusions: This study in the largest cohort of male patients with PBS receiving RRT to date demonstrates that outcomes are comparable with other congenital anomalies of the kidney and urinary tract, except for a slightly higher mortality risk compared with patients with COU. [ABSTRACT FROM AUTHOR]

Background: We aimed to study the impact of obesity on urinary excretion of angiotensinogen (U-AGT) in prepubertal children, focusing on the duration of obesity and gender. Also, we aimed to evaluate whether plasma angiotensinogen (P-AGT) and hydrogen peroxide (HO) play a role in the putative association. Methods: Cross-sectional evaluation of 305 children aged 8-9 years (160 normal weight, 86 overweight, and 59 obese). Anthropometric measurements and 24-h ambulatory blood pressure monitoring were performed. Angiotensinogen (AGT) was determined by a commercial enzyme-linked immunosorbent assay (ELISA) kit and HO by a microplate fluorometric assay. Results: U-AGT and P-AGT levels were similar across body mass index (BMI) groups and between sexes. However, boys who were overweight/obese since the age of 4 years presented lower levels of U-AGT compared with those of normal weight at the same age. In children who were overweight/obese since the age of 4, urinary HO decreased with P-AGT. Conclusions: A higher duration of obesity was associated with decreased U-AGT in boys, thus reflecting decreased intrarenal activity of the renin-angiotensin system. Also, children with a longer duration of obesity showed an inverse association between urinary HO and P-AGT. Future studies should address whether these results reflect an early compensatory mechanism to limit obesity-triggered renal dysfunction. [ABSTRACT FROM AUTHOR]

Background: Urinary neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-beta-D-glucosaminidase (NAG), and interleukin 18 (IL-18) were found to be useful for early detection of acute kidney injury (AKI). The objective of this study was to determine the predictive ability of biomarkers for mortality and variation in levels in relation to different stages of AKI, need for dialysis, etiologies, and with duration of hospital stay. Methods: Urinary NGAL, NAG, and IL-18 levels were measured in 50 children with AKI and 30 age- and gender-matched healthy controls. AKI was classified as per pediatric Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria. Results: Median NGAL, NAG, and IL-18 values were significantly increased in AKI patients compared with controls ( p < 0.001), with significant increase among risk, injury, and failure stages. Nonsurvivors had significantly higher median levels of NGAL ( p = 0.008) and NAG ( p = 0.018) than survivors. NGAL had highest area under the curve (AUC) at 0.750 [confidence interval (CI) 0.580-0.920], followed by NAG at 0.724 (CI 0.541-0.907), with sensitivity and specificity of 75 % each; and IL-18 (AUC 0.688, CI 0.511-0.864), with sensitivity 62.5 % and specificity 70.8 %, for predicting mortality. Values were significantly higher in patients who required peritoneal dialysis (PD) than in those in whom it was not indicated. Levels were comparable among different etiologies. Only NGAL level was found to be a significant risk factor associated with longer duration of hospital stay. Conclusions: Urinary NGAL and NAG had modest predictive ability for mortality. Children requiring dialysis had significantly raised levels, and the NGAL level had significant association with duration of hospital stay. [ABSTRACT FROM AUTHOR]

Background: Congenital nephrotic syndrome (CNS) of the Finnish type, NPHS1, is the most severe form of CNS. Outcomes of renal replacement therapy (RRT) in NPHS1 patients in Europe were analysed using data from the ESPN/ERA-EDTA Registry. As NPHS1 is most prevalent in Finland and the therapeutic approach differs from that in many other countries, we compared outcomes in Finnish and other European patients. Methods: NPHS1 mutations were confirmed in 170 children with CNS who initiated RRT (dialysis or renal transplantation) between 1991 and 2012. Finnish ( n = 66) and non-Finnish NPHS1 patients ( n = 104) were compared with respect to treatment policy, age at first RRT and renal transplantation (RTX), patient and graft survival, estimated glomerular filtration rate (eGFR) and growth. Age-matched patients with congenital anomalies of the kidney and urinary tract (CAKUT) served as controls. Results: Finnish NPHS1 patients were significantly younger than non-Finnish patients, both at the start of RRT and at the time of RTX. We found similar overall 5-year patient survival on RRT (91 %) and graft survival (89 %) in both NPHS1 groups and CAKUT controls. At the start of RRT, height standard deviation score (SDS) was higher in Finnish patients than in non-Finnish patients (mean [95 % CI]: −1.31 [−2.13 to −0.49] and −3.0 [−4.22 to −1.91], p < 0.01 respectively), but not at 5 years of age. At 5 years of age height and body mass index (BMI) SDS were similar to those of CAKUT controls. Conclusions: Overall, 5-year patient and graft survival of both Finnish and non-Finnish NPHS1 patients on RRT were excellent and comparable with CAKUT patients with equally early RRT onset and was independent of the timing of RRT initiation and RTX. [ABSTRACT FROM AUTHOR]

End-stage renal disease (ESRD) in children is a medically challenging condition. Due to its rarity and special features, methodologically sound collaborative studies are required. In 2007, a new European registry of pediatric renal replacement therapy (RRT), the ESPN/ERA-EDTA Registry, was launched. In recent years, the Registry has provided comprehensive data on incidence, prevalence, patient characteristics, RRT modalities, and mortality in pediatric ESRD, along with relevant insights into cardiovascular risk, anemia, nutrition and growth, transplantation outcomes, and rare diseases. In this review, we describe the study design and structure underlying the ESPN/ERA-EDTA Registry, summarize the major research findings from more than 20 publications, and discuss current limitations and the future challenges to overcome. [ABSTRACT FROM AUTHOR]

Background: In children acute liver failure is a rare but life-threatening condition from which two-thirds do not recover with supportive therapy. Treatment is limited by the availability of liver transplants. Molecular adsorbent recirculating system (MARS) dialysis is a bridge to transplantation that enhances the chances of survival during the waiting period for a transplant, although it cannot improve survival. Open albumin dialysis (OPAL) is a new mode of albumin dialysis developed to further improve dialysis efficiency. Case diagnosis/treatment: We report a paediatric case of acute-on-chronic liver failure and compare the two modes of albumin dialysis, namely, the MARS and OPAL, used to treat this patient's cholestatic pruritus. Removal of total and direct bilirubin, ammonia and bile acids were measured by serial blood tests. There was an increased removal of bile acids with the OPAL mode, whereas the removal of total and direct bilirubin and ammonia was similar in both modes. The patient reported better improvement in pruritus following OPAL compared to dialysis with the MARS. Conclusion: OPAL may offer a better solution than the MARS in the treatment of refractory pruritus in liver failure. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated with high patient morbidity and mortality. There is no consensus on the best RRT modality for pediatric AKI. Methods: The efficacy and safety of continuous peritoneal dialysis (cPD) and daily intermittent hemodialysis (dHD) were compared in 136 children aged 1 month to 16 years requiring RRT for AKI. Mortality, risk factors and causes of death, 1-month and 3-month renal recovery rates, and technique-related complications were assessed. Results: Uremia control and the rate of catheter-related complications were comparable in the groups. Thirty-day survival was 60.7 % (51 out of 84) with cPD and 36.5 % (19 out of 52) with dHD ( p = 0.019). Although age <1 year, extended time lag from disease onset to RRT initiation, mechanical ventilation, and extended vasopressor dependence independently predicted death, adjusted mortality was higher with dHD relative to cPD (hazard ratio [HR] 1.75, 95%CI 1.18-2.84, p = 0.022). Almost all fatalities in the dHD group (94 %) occurred during or within an hour of a HD session. Renal function normalized in 27 % of survivors after 4 weeks and in 51 % after 3 months. The risk of permanent end-stage renal disease was increased in patients with an intrinsic renal cause of AKI (HR 2.72; 95 % CI 1.37-3.83; p = 0.029) and in those with delayed RRT initiation (HR 2.17; 95 % CI 123-2.93; p = 0.015), but did not differ between patients treated with dHD and cPD. Conclusions: Favorable patient survival with cPD compared with dHD in children treated for AKI was evident in this study. [ABSTRACT FROM AUTHOR]

Background: Glomerular filtration rate (GFR) is conventionally indexed to body surface area (BSA), but this may lead to biased results when applied to subjects of abnormal body size. The aim of our study was to examine the impact of normalization to the BSA and alternative body size descriptors on measured and estimated GFR in overweight and obese children. Methods: This was a cross-sectional study of 313 children aged 8-9 years old. GFR was measured by 24-h creatinine clearance (CrCl) and additionally estimated from serum creatinine and cystatin C (CysC) using the combined Zappitelli formula, both as absolute values and adjusted to various body size descriptors. The results were compared between 163 normal-weight, 89 overweight and 61 obese children. Results: Compared to the normal-weight children, mean absolute GFR (both measured and estimated) was higher in the overweight and obese children, whereas BSA-adjusted GFR was lower. Linear regression models fitted in normal-weight children revealed equally close associations between absolute GFR and squared height, ideal body weight (IBW) and BSA derived from IBW. Normalization of GFR to the IBW-derived BSA completely eliminated the discrepancy between absolute and BSA-indexed GFR in overweight and obese children. Conclusions: Indexing of GFR to BSA calculated from the ideal-rather than actual-body weight is a promising approach to avoid overcorrection when studying obese children. Further studies should assess the accuracy of this approach across the full range of age and BMI distribution. [ABSTRACT FROM AUTHOR]

The genome-wide association study (GWAS) has become an established scientific method that provides an unbiased screen for genetic loci potentially associated with phenotypes of clinical interest, such as chronic kidney disease (CKD). Thus, GWAS provides opportunities to gain new perspectives regarding the genetic architecture of CKD progression by identifying new candidate genes and targets for intervention. As such, it has become an important arm of translational science providing a complementary line of investigation to identify novel therapeutics to treat CKD. In this review, we describe the method and the challenges of performing GWAS in the pediatric CKD population. We also provide an overview of successful GWAS for kidney disease, and we discuss the established pediatric CKD cohorts in North America and Europe that are poised to identify genetic risk variants associated with CKD progression. [ABSTRACT FROM AUTHOR]

Background: Limited prospective data are available on the long-term safety of darbepoetin alfa (DA) for treating anemia in children with chronic kidney disease (CKD). Methods: In this prospective, phase IV, observational registry study, children ≤16 years of age with CKD anemia and receiving DA were observed for ≤2 years. Adverse events (AEs), DA dosing, hemoglobin (Hb) concentrations, and transfusions were recorded. Results: A total of 319 patients were included in the analysis (mean age, 9.1 years), 158 (49.5 %) of whom were on dialysis at study entry. Of 434 serious AEs reported in 162 children, the most common were peritonitis (10.0 %), gastroenteritis (6.0 %), and hypertension (4.1 %). Six patients (1.9 %) died (unrelated to DA). Four patients (1.3 %) experienced six serious adverse drug reactions. The geometric mean DA dose range was 1.4-2.0 μg/kg/month. Mean baseline Hb concentration was 11.1 g/dl; mean values for children receiving and not receiving dialysis at baseline ranged between 10.9 and 11.5 g/dl and 11.2-11.7 g/dl, respectively. Overall, 48 patients (15.0 %) received ≥1 transfusion. Conclusions: No new safety signals for DA were identified in children receiving DA for CKD anemia for ≤2 years. Based on Hb concentrations and transfusion requirements, DA was effective at managing anemia in these patients. [ABSTRACT FROM AUTHOR]

Background: Fibrogenic cytokines are recognized as putative drivers of disease activity and histopathological deterioration in various kidney diseases. We compared urinary transforming growth factor β1 (U-TGF-β1) and endothelin 1 (U-ET-1) levels across body mass index classes and assessed their association with the level of urinary angiotensinogen (U-AGT), a biomarker of intrarenal renin-angiotensin-aldosterone system (RAAS). Methods: The was a cross-sectional evaluation of 302 children aged 8-9 years. Ambulatory blood pressure (BP), insulin resistance (HOMA-IR), aldosterone level and renal function were evaluated. U-ET-1, U-TGF-β1 and U-AGT levels were determined by immunoenzymatic methods. Results: Obese children presented with the lowest levels of U-ET-1 and U-TGF-β1, but the difference was only significant for U-ET-1. In obese children, the median levels of both U-ET-1 and U-TGF-β1 tended to increase across tertiles (T1-T3) of U-AGT (U-ET-1: T1, 19.9 (14.2-26.3); T2, 32.5 (23.3-141.6); T3, 24.8 (18.7-51.5) ng/g creatinine, p = 0.007; U-TGF-β1: T1, 2.2 (1.8-4.0); T2, 4.3 (2.7-11.7); T3, 4.9 (3.8-10.1) ng/g creatinine, p = 0.004]. In multivariate models, in the obese group, U-ET-1 was associated with HOMA-IR and aldosterone and U-AGT levels, and U-TGF-β1 was associated with U-AGT levels and 24 h-systolic BP. Conclusions: Whereas the initial hypothesis of higher levels of urinary fibrogenic cytokines in obese children was not confirmed in our study, both TGF-β1 and U-ET-1 levels were associated with U-AGT level, which likely reflects an early interplay between tissue remodeling and RAAS in obesity-related kidney injury. [ABSTRACT FROM AUTHOR]

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early, or who are small-for-date newborns, have a relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy-makers, and caregivers about the needs and possibilities surrounding kidney disease in childhood. [ABSTRACT FROM AUTHOR]

Background: Corticosteroid therapy can cause behavioural abnormalities in children with nephrotic syndrome. The objective of this study was to explore the timing of the appearance of abnormalities in their first episode. Methods: Forty-five children with a first episode of idiopathic nephrotic syndrome (30 aged 2-5 and 15 aged 6-14 years) were assessed for behavioural problems using the Child Behaviour Checklist (CBCL) before, and after 6 and 12 weeks of oral steroid treatment. Sixty healthy children were included as controls. Results: In both age groups, marked abnormalities of externalising behaviour were noticed, specifically in the domains of aggressive behaviour and attention problems. Clinical range or borderline externalising abnormalities were present in 73 % of the younger children and 60 % of the schoolchildren after 6 weeks of treatment. In the schoolchildren, abnormal internalising behaviour was also noted at 6 weeks, in 40 % at borderline level and in 20 % within the clinical range. Elevated scores were observed for the anxious/depressed and withdrawn/depressed domains. Most changes persisted at the 12-week observation. Conclusions: Children of both age groups showed significant attention problems and aggressive and abnormal externalising behaviour within 6 weeks of starting treatment. Parents should be informed and counselled about this potential adverse effect of steroid therapy. [ABSTRACT FROM AUTHOR]

Background: Our aim was to determine the prevalence of sub-target hemoglobin (Hb) levels in children with a renal allograft and to identify potential determinants associated with these Hb levels. Methods: Data from 3669 children with a functioning renal allograft, aged <18 years between 1 January 2000 and 31 December 2012, from 20 European countries were retrieved from the ESPN/ERA-EDTA Registry, providing 16,170 Hb measurements. Results: According to the NKF/KDOQI classification and the UK-NICE guidelines, 49.8 and 7.8 % of the patients, respectively, were anemic. Hb levels were strongly associated with graft function, with Hb levels of 12.6 g/dl in children with chronic kidney disease (CKD) stage 1, declining to 10.7 g/dl in children with CKD stage 5 ( P < 0.001). Higher Hb levels were associated with the use of tacrolimus compared to ciclosporin (0.14 g/dl; 95 % confidence interval 0.02-0.27; P = 0.002). Low Hb levels were associated with an increased risk of graft failure ( P = 0.01) or combined graft failure and death ( P < 0.01), but not with death alone (not significant). Conclusions: Anemia is present in a significant proportion of European pediatric kidney transplant recipients and is associated with renal allograft dysfunction and type of immunosuppressants used. In our patient cohort, higher Hb levels were associated with better graft and patient survival and less hypertension. [ABSTRACT FROM AUTHOR]

Background: Most modifiable risk factors for high blood pressure (BP), such as obesity and salt intake, are imprinted in childhood and persist into adulthood. The aim of our study was to evaluate the intake of salt in children and to assess its impact on BP taking into account gender and nutritional status. Methods: A total of 298 children aged 8-9 years were evaluated in a cross-sectional study. Anthropometric measurements and 24-h ambulatory monitoring were performed, and salt intake was determined by 24-h urinary sodium excretion. Results: The average estimated salt intake among the entire cohort of children enrolled in the study was 6.5 ± 2.2 g/day, and it was significantly higher in boys than in girls (6.8 ± 2.4 vs. 6.1 ± 1.9 g/day, respectively; p = 0.018) and in overweight/obese children than in normal weight children (6.8 ± 2.4 vs. 6.1 ± 2.0 g/day, respectively; p = 0.006). Salt intake exceeded the upper limit of the US Dietary Reference Intake in 72 % of children. Daytime systolic BP increased by 1.00 mmHg (95 % confidence interval 0.40-1.59) per gram of daily salt intake in overweight/obese boys, but not in normal weight boys or in girls. Conclusions: Our results demonstrate an extremely high salt intake among 8- to 9-year-old Portuguese children. Higher salt intake was associated with higher systolic BP in boys, specifically in those who were overweight/obese. Longitudinal studies are needed to further evaluate the causal relationship between obesity and high BP and the mechanism by which salt intake modulates this relationship. Nonetheless, based on our results, we urge that dietary salt reduction interventions, along with measures to fight the global epidemic of obesity, be implemented as early in life as possible. [ABSTRACT FROM AUTHOR]

Background: Recombinant human (rh) growth hormone (GH) raises the glomerular filtration rate (GFR) in healthy individuals. Concern has been raised that long-term rhGH treatment in short children with chronic kidney disease (CKD) may accelerate the progression of CKD via induction of glomerular hyperfiltration. Patients and methods: We compared the decline in GFR in children with CKD enrolled in two large clinical studies with (KIGS registry) and without (ESCAPE trial) concomitant rhGH treatment and followed for up to 10 years. Estimated GFR (eGFR) was determined at yearly intervals. The annual decline in eGFR was analyzed cross-sectionally for up to 10 years and longitudinally for 5 years. Results: In the KIGS registry 367 patients with CKD stages II-IV (mean age 8.0 years; 72 % boys; mean eGFR 38.4 ml/min/1.73 m) were treated with 0.33 mg rhGH/kg per week for at least 1 year. In the ESCAPE trial 274 non-rhGH-treated patients with CKD stages II-IV (mean age 11.6 years; 61 % boys; mean GFR 47.3 ml/min/1.73 m) were followed for at least 1 year. At the 5-year follow-up, the mean loss of eGFR in the KIGS children receiving continuous rhGH treatment ( n = 97) did not differ significantly from that in the controls ( n = 113) in the ESCAPE trial (−5.8 vs. −8.6 ml/5 years, respectively; p = 0.17). Absolute height and eGFR at baseline were significant correlates of the annual eGFR loss (model R =0.121). Conclusions: Long-term rhGH-treatment does not accelerate the decline in GFR in short children with CKD. Height and baseline eGFR are significant predictors of the loss of GFR in CKD patients. [ABSTRACT FROM AUTHOR]

There is a growing international agreement on the need to provide greater access to research data and bio-specimen collections to optimize their long-term value and exploit their potential for health discovery and validation. This is especially evident for rare disease research. Currently, the rising value of data and bio-specimen collections does not correspond with an equal increase in data/sample-sharing and data/sample access. Contradictory legal and ethical frameworks across national borders are obstacles to effective sharing: more specifically, the absence of an integrated model proves to be a major logistical obstruction. The Charter intends to amend the obstacle by providing both the ethical foundations on which data sharing should be based, as well as a general Material and Data Transfer Agreement (MTA/DTA). This Charter is the result of a careful negotiation of different stakeholders' interest and is built on earlier consensus documents and position statements, which provided the general international legal framework. Further to this, the Charter provides tools that may help accelerate sharing. The Charter has been formulated to serve as an enabling tool for effective and transparent data and bio-specimen sharing and the general MTA/DTA constitutes a mechanism to ensure uniformity of access across projects and countries, and may be regarded as a consistent basic agreement for addressing data and material sharing globally. The Charter is forward looking in terms of emerging issues from the perspective of a multi-stakeholder group, and where possible, provides strategies that may address these issues. [ABSTRACT FROM AUTHOR]

Background: Soluble urokinase-type plasminogen activator receptor (suPAR) could be a causative factor in idiopathic focal segmental glomerulosclerosis (FSGS). It is currently unknown to what extent suPAR levels could be affected by treatment with immunosuppressive drugs such as cyclosporin A (CsA) and mycophenolate mofetil (MMF). Treatment with CsA, but not MMF, is accompanied by nephrotoxicity, and since suPAR levels correlate with glomerular filtration rate (GFR), treatment with these drugs could indirectly modulate suPAR levels by their effect on renal function. Methods: We measured suPAR levels in a recent prospective multicenter crossover trial comparing the efficacy of MMF and CsA in pediatric patients with minimal change disease (MCD) and frequently relapsing steroid-sensitive nephrotic syndrome (FR-SSNS). All patients had biopsy-proven MCD and normal renal function; they were treated with each drug for 1 year in a crossover study design. Serum suPAR levels were measured before and after 1 year of therapy with MMF ( n = 40) and CsA ( n = 35). Results: The suPAR levels decreased after 1 year of treatment with MMF ( p < 0.05). Conversely, suPAR levels increased after 1 year of treatment with CsA in the same patients ( p = 0.01). These changes in suPAR levels were not correlated to the estimated glomerular filtration rate (eGFR) or changes in the GFR. Conclusions: Data from this prospective randomized trial suggest that treatment with MMF and CsA is associated with different effects on suPAR levels in children with MCD and that these are independent of their effects on GFR. [ABSTRACT FROM AUTHOR]