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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. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia is an important and modifiable risk factor for CVD in children with CKD. Methods: In a cross-sectional study of baseline serum lipid levels in a large prospective cohort study of children with stage 3–5 (predialysis) CKD, frequencies of abnormal lipid levels and types of dyslipidemia were analyzed in the entire cohort and in subpopulations defined by fasting status or by the presence of nephrotic range proteinuria. Associated clinical and laboratory characteristics were determined by multivariable linear regression analysis. Results: A total of 681 patients aged 12.2 ± 3.3 years with a mean eGFR of 26.9 ± 11.6 ml/min/1.73 m2 were included. Kidney diagnosis was classified as CAKUT in 69%, glomerulopathy in 8.4%, and other disorders in 22.6% of patients. Nephrotic range proteinuria (defined by a urinary albumin/creatinine ratio > 1.1 g/g) was present in 26.9%. Dyslipidemia was found in 71.8%, and high triglyceride (TG) levels were the most common abnormality (54.7%). Fasting status (38.9%) had no effect on dyslipidemia status. Except for a significant increase in TG in more advanced CKD, lipid levels and frequencies of dyslipidemia were not significantly different between CKD stages. Hypertriglyceridemia was associated with younger age, lower eGFR, shorter duration of CKD, higher body mass index (BMI-SDS), lower serum albumin, and higher diastolic blood pressure. Conclusions: Dyslipidemia involving all lipid fractions, but mainly TG, is present in the majority of patients with CKD irrespective of CKD stage or fasting status and is significantly associated with other cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Despite significant medical and technical improvements in the field of dialysis, the morbidity and mortality among patients with chronic kidney disease (CKD) stage 5 on dialysis remains extremely high. Hemodiafiltration (HDF), a dialysis method that combines the two main principles of hemodialysis (HD) and hemofiltration—diffusion and convection—has had a positive impact on survival when delivered with a high convective dose. Improved outcomes with HDF have been attributed to the following factors: HDF removes middle molecular weight uremic toxins including inflammatory cytokines, increases hemodynamic stability, and reduces inflammation and oxidative stress compared to conventional HD. Two randomized trials in adults have shown improved survival with HDF compared to high-flux HD. A large prospective cohort study in children has shown that HDF attenuated the progression of cardiovascular disease, improved bone turnover and growth, reduced inflammation, and improved blood pressure control compared to conventional HD. Importantly, children on HDF reported fewer headaches, dizziness, and cramps; had increased physical activity; and improved school attendance compared to those on HD. In this educational review, we discuss the technical aspects of HDF and results from pediatric studies, comparing outcomes on HDF vs. conventional HD. Convective volume, the cornerstone of treatment with HDF and a key determinant of outcomes in adult randomized trials, is discussed in detail, including the practical aspects of achieving an optimal convective volume. [ABSTRACT FROM AUTHOR]

Assess creatinine levels in French children with Down syndrome (DS) on the basis of the relationship between creatinine levels and age. The study included 279 children with DS aged 0 to 10 years who had been regularly monitored between 2004 and 2021 in a single genetics department and who had had at least one creatinine measurement. The creatinine level curves were established by estimating the median and the quantiles of order 2.5 and 97.5% according to age. A Generalized Additive Model for Location, Scale, and Shape was used. The results showed higher creatinine levels in children with DS than in children from the general population. Conclusion: The present results allow to propose an original chart of creatinine levels according to age in French children with DS, which should help optimize their medical management and improve the early detection of renal diseases. What is Known: • Creatinine is a product of muscle breakdown and depends on muscle mass and children with Down syndrome have muscle and growth characteristics that differ from those of the general paediatric population. • Serum creatinine values in Japanese children with DS are higher than those of children from the general Japanese population. What is New: • Creatinine values in French children with DS are higher than those of children from the general French population. • The proposed original chart for creatinine values according to age, specifically designed for individuals up to 10 years old, should serve for further investigation, prevention, and follow-up of children with DS. [ABSTRACT FROM AUTHOR]

Patients with Down syndrome (DS) are at risk of multiorgan dysfunction; kidney and urological impairment are common. This is due to a likely increased risk of congenital kidney and urological malformations (odds ratio of 4.5 compared to the general population in one study), more frequent associated comorbidities at risk of kidney dysfunction (such as prematurity in 9–24% of children, intrauterine growth retardation or low birth weight in 20%, and congenital heart disease in 44%), and more frequent lower urinary tract dysfunction (reported in 27–77% of children with DS). If present, malformations and comorbidities at risk of kidney dysfunction warrant regular kidney monitoring in addition to their treatment. Serum creatinine in children with DS has been shown to be higher than in the general population and asymptomatic hyperuricemia is reported in 12–33% of children or young adults with DS. Moreover cryptorchidism and testicular cancer are also more common and should be detected by clinical examination. Thus, persons with DS at risk of presenting kidney and urological impairment should be identified by prenatal ultrasonography, comorbidities at risk of kidney sequelae considered, and during regular medical follow-up, clinically examined and questioned to diagnose testicular anomalies and lower urinary tract dysfunction. This is of importance as such kidney and urological impairments are associated with impaired quality of life and mental health, and risk of kidney failure. [ABSTRACT FROM AUTHOR]

Background: From 2006 to 2020, 24% of children starting haemodialysis in France weighed < 20 kg. Most new-generation long-term haemodialysis machines do not propose paediatric lines anymore but Fresenius has validated two devices for use in children above 10 kg. Our aim was to compare the daily use of these two devices in children < 20 kg. Methods: Retrospective single-center evaluation of daily practice with Fresenius 6008® machines, and low-volume paediatric sets (83 mL), as compared to 5008® machines with paediatric lines (108 mL). Each child was treated randomly with both generators. Results: A total of 102 online haemodiafiltration sessions were performed over 4 weeks in five children (median body weight 12.0 [range 11.5–17.0] kg). Arterial aspiration and venous pressures were maintained respectively over − 200 mmHg and under 200 mmHg. For all children, blood flow and volume treated per session were lower with 6008® vs. 5008® (p < 0.001), median difference between the two devices being 21%. In the four children treated in post-dilution mode, substituted volume was lower with 6008® (p < 0.001, median difference: 21%). Effective dialysis time was not different between the two generators; however, the difference between total duration of session and dialysis effective time was slightly higher (p < 0.05) with 6008® for three patients, due to treatment interruptions. Conclusion: These results suggest that children between 11 and 17 kg should be treated with paediatric lines on 5008® if possible. They advocate for modification of the 6008 paediatric set to decrease resistance to blood flow. The possibility to use 6008® with paediatric lines in children below 10 kg deserves further studies. [ABSTRACT FROM AUTHOR]

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 (β = 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. [ABSTRACT FROM AUTHOR]

Background: Infants with chronic kidney disease (CKD) form a vulnerable population who are highly prone to mineral and bone disorders (MBD) including biochemical abnormalities, growth retardation, bone deformities, and fractures. We present a position paper on the diagnosis and management of CKD-MBD in infants based on available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce. Methods: PICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and relevant literature searches performed covering a population of infants below 2 years of age with CKD stages 2–5 or on dialysis. Clinical practice points (CPPs) were developed and leveled using the American Academy of Pediatrics grading matrix. A Delphi consensus approach was followed. Results: We present 34 CPPs for diagnosis and management of CKD-MBD in infants, including dietary control of calcium and phosphate, and medications to prevent and treat CKD-MBD (native and active vitamin D, calcium supplementation, phosphate binders). Conclusion: As there are few high-quality studies in this field, the strength of most statements is weak to moderate, and may need to be adapted to individual patient needs by the treating physician. Research recommendations to study key outcome measures in this unique population are suggested. [ABSTRACT FROM AUTHOR]

Background: The Cardio-Renal Pediatric Dialysis Emergency Machine (CA.R.P.E.D.I.E.M.®) device is a continuous kidney replacement therapy (CKRT) equipment dedicated to neonates and small infants. This study aimed to assess the effectiveness, feasibility, outcomes, and technical considerations relating to CARPEDIEM® use. Methods: This retrospective multicenter study included 19 newborns and six infants receiving CARPEDIEM® in five French pediatric and neonatal intensive care units. Laboratory parameters were collected at the initiation and end of the first CARPEDIEM® session. Results are presented as median [IQR] (range). Results: At initiation, age was 4 days [2–13] (1–1134) with a body weight of 3.3 kg [2.5–4] (1.3–11.1). Overall, 131 sessions and 2125 h of treatment were performed. Treatment duration per patient was 42 h [24–91] (8–557). Continuous veno-venous hemofiltration (CVVH) was performed in 20 children. Blood flow rate was 8 mL/kg/min [6–9] (3–16). The effluent flow rate for CVVH was 74 mL/kg/h [43–99] (28–125) and net ultrafiltration (UF) 6 mL/kg/h [2–8] (1–12). In the five children treated by hemodialysis, the blood and dialysate flow rates were 6 mL/kg/min [5–7] (4–7) and 600 mL/h [300–600] (120–600), respectively, while session duration was 8 h [6–12] (2–24). Most infants required a catheter between 4.5 and 6.5 French. Hemodynamic instability with a need for volume replacement occurred in 31 sessions (23%). Thrombocytopenia was observed in 29 sessions (22%). No hemorrhage occurred; all the patients survived the sessions, but only eight patients (32%) were alive at hospital discharge. Conclusions: These data confirm that the use of CARPEDIEM® is safe and effective in critically ill neonates and infants. [ABSTRACT FROM AUTHOR]

Background: Pediatric ANCA vasculitis is a rare group of diseases with a scarcity of data in children. Annual incidence appeared to increase in the last several years, placing higher interest in the clinical and therapeutical outcomes of the disorder. Also, the growing use of rituximab questions the latest outcomes in these diseases. We therefore conducted a retrospective study to better understand the current characteristics, management, and the latest outcomes of the disorder. Methods: We conducted a 9-year retrospective study of 46 children in 14 different centers across France to describe their clinical and laboratory presentations, therapeutic regimens, and kidney outcome. Results: P-ANCA appeared to be a potential marker for higher relapse risk. Compared to adults, we found that ear-nose-throat presentations were frequent (45.7%) and more severe. Despite an evolution in the treatment management, kidney outcome remained poor with a substantial proportion of chronic kidney disease (54.8% at 1 year). Mortality stays low with 3 patients (6.5%) deceased at the end of our study. Conclusion: Clinical presentation was as previously described and time to diagnosis remains long. P-ANCA is a statistically significant marker for increased relapse risk. We observed a modification in the treatment regimens over the past several years with a growing use of rituximab and a decreasing use of cyclophosphamide. Despite these changes, kidney outcome remains poor and prospective studies should be conducted to assess the most appropriate therapeutic modality for each patient. [ABSTRACT FROM AUTHOR]

Alagille syndrome (ALGS) is an autosomal dominant, multisystemic disease with a high interindividual variability. The two causative genes JAG1 and NOTCH2 are expressed during kidney development, can be reactivated during adulthood kidney disease, and Notch signalling is essential for vascular morphogenesis and remodelling in mice. Liver disease is the most frequent and severe involvement; neonatal cholestasis occurs in 85% of cases, pruritus in 74%, xanthomas in 24% of cases, and the cumulative incidences of portal hypertension and liver transplantation are 66% and 50% respectively at 18 years of age. Stenosis/hypoplasia of the branch pulmonary arteries is the most frequent vascular abnormality reported in ALGS. Kidney involvement is present in 38% of patients, and can reveal the disease. Congenital anomalies of the kidney and urinary tract is reported in 22% of patients, hyperchloremic acidosis in 9%, and glomerulopathy and/or proteinuria in 6%. A decreased glomerular filtration rate is reported in 10% of patients and is more frequent after liver transplantation for ALGS than for biliary atresia. Kidney failure has been frequently reported in childhood and adulthood. Renal artery stenosis and mid aortic syndrome have also frequently been reported, often associated with hypertension and stenosis and/or aneurysm of other large arteries. ALGS patients require kidney assessment at diagnosis, long-term monitoring of kidney function and early detection of vascular complications, notably if they have undergone liver transplantation, to prevent progression of chronic kidney disease and vascular complications, which account for 15% of deaths at a median age of 2.2 years in the most recent series.A higher resolution version of the Graphical abstract is available as Supplementary informationA higher resolution version of the Graphical abstract is available as Supplementary informationGraphical abstract: Alagille syndrome (ALGS) is an autosomal dominant, multisystemic disease with a high interindividual variability. The two causative genes JAG1 and NOTCH2 are expressed during kidney development, can be reactivated during adulthood kidney disease, and Notch signalling is essential for vascular morphogenesis and remodelling in mice. Liver disease is the most frequent and severe involvement; neonatal cholestasis occurs in 85% of cases, pruritus in 74%, xanthomas in 24% of cases, and the cumulative incidences of portal hypertension and liver transplantation are 66% and 50% respectively at 18 years of age. Stenosis/hypoplasia of the branch pulmonary arteries is the most frequent vascular abnormality reported in ALGS. Kidney involvement is present in 38% of patients, and can reveal the disease. Congenital anomalies of the kidney and urinary tract is reported in 22% of patients, hyperchloremic acidosis in 9%, and glomerulopathy and/or proteinuria in 6%. A decreased glomerular filtration rate is reported in 10% of patients and is more frequent after liver transplantation for ALGS than for biliary atresia. Kidney failure has been frequently reported in childhood and adulthood. Renal artery stenosis and mid aortic syndrome have also frequently been reported, often associated with hypertension and stenosis and/or aneurysm of other large arteries. ALGS patients require kidney assessment at diagnosis, long-term monitoring of kidney function and early detection of vascular complications, notably if they have undergone liver transplantation, to prevent progression of chronic kidney disease and vascular complications, which account for 15% of deaths at a median age of 2.2 years in the most recent series.A higher resolution version of the Graphical abstract is available as Supplementary informationA higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Children with chronic kidney disease (CKD) suffer from inflammation and reactive metabolite-induced stress, which massively accelerates tissue and vascular aging. Peritoneal dialysis (PD) is the preferred dialysis mode in children, but currently used PD fluids contain far supraphysiological glucose concentrations for fluid and toxin removal and glucose degradation products (GDP). While the peritoneal membrane of children with CKD G5 exhibits only minor alterations, PD fluids trigger numerous molecular cascades resulting in major peritoneal membrane inflammation, hypervascularization, and fibrosis, with distinct molecular and morphological patterns depending on the GDP content of the PD fluid used. PD further aggravates systemic vascular disease. The systemic vascular aging process is particularly pronounced when PD fluids with high GDP concentrations are used. GDP induce endothelial junction disintegration, apoptosis, fibrosis, and intima thickening. This review gives an overview on the molecular mechanisms of peritoneal and vascular transformation and strategies to improve peritoneal and vascular health in patients on PD. [ABSTRACT FROM AUTHOR]

Background: Atypical hemolytic and uremic syndrome (aHUS), a thrombotic micro-angiopathy (TMA) caused by deregulation in the complement pathway, is sometimes due to the presence of anti-complement factor H (CFH) auto-antibodies. The "standard" treatment for such aHUS combines plasma exchange therapy and immunosuppressive drugs. Eculizumab, a monoclonal antibody that blocks the terminal pathway of the complement cascade, could be an interesting alternative in association with an immunosuppressive treatment for maintenance regimen. Case–diagnosis/treatment: We report on two children, diagnosed with mildly severe aHUS due to anti-CFH antibodies, who were treated with the association eculizumab–mycophenolate mofetil (MMF). Neither side effects nor relapses were observed during the 3 years of follow-up; MMF was even progressively tapered and withdrawn successfully in one patient. Conclusions: The association of eculizumab and MMF appears to be an effective and safe option in pediatric cases of aHUS due to anti-CFH antibodies of mild severity. [ABSTRACT FROM AUTHOR]

Introduction: In nephropathic cystinosis (NC), adherence to cysteamine remains challenging; poor adherence is worsening the disease progression with a decline of kidney function and increase of extrarenal morbidities. Our objective was to describe adherence to cysteamine in NC patients, using electronic monitoring systems. Methods: Patients with confirmed NC, aged > 4 years and receiving oral cysteamine (short acting or delayed release formulation as standard of care) from 3 French reference centers, were included. Adherence to treatment was primarily assessed as the percentage of days with a good adherence score, adherence score rating from 0 (poor) to 2 (good). A descriptive analysis was performed after 1-year follow-up. Results: Seventeen patients (10 girls, median age: 13.9 (5.4–33.0) years) were included. Median age at diagnosis was 17.0 (3.0–76.9) months and age at start of cysteamine was 21.0 (15.5–116.3) months. Median daily dose of cysteamine was 1.05 (0.55–1.63) g/m2/day. Over the year, the median percentage of days with a good adherence score was 80 (1–99)% decreasing to 68 (1–99)% in patients > 11 years old. The median of average number of hours covered by treatment in a day was 22.5 (6.1–23.9) versus 14.9 (9.2–20.5) hours for delayed release versus short acting cysteamine. Conclusion: Our data are the first describing a rather good adherence to cysteamine, decreasing in adolescents and adults. We described a potential interest of the delayed release formulation. Our data highlight the need for a multidisciplinary approach including therapeutic education and individualized approaches in NC patients transitioning to adulthood. Graphical abstract [ABSTRACT FROM AUTHOR]

Hyperphosphatemia is common in chronic kidney disease (CKD). Often seen as the "silent killer" because of its dramatic effect on vascular calcifications, hyperphosphatemia explains, at least partly, the onset of the complex mineral and bone disorders associated with CKD (CKD-MBD), together with hypocalcemia and decreased 1-25(OH)2 vitamin D levels. The impact of CKD-MBD may be immediate with abnormalities of bone and mineral metabolism with secondary hyperparathyroidism and increased FGF23 levels, or delayed with poor growth, bone deformities, fractures, and vascular calcifications, leading to increased morbidity and mortality. The global management of CKD-MBD has been detailed in international guidelines for adults and children, however, with difficulties to obtain an agreement on the ideal PTH targets. The clinical management of hyperphosphatemia is a daily challenge for nephrologists and pediatric nephrologists, notably because of the phosphate overload in occidental diets that is mainly due to the phosphate "hidden" in food additives. The management begins with a dietary restriction of phosphate intake, and is followed by the use of calcium-based and non-calcium-based phosphate binders, and/or the intensification of dialysis. The objective of this review is to provide an overview of the pathophysiology of hyperphosphatemia in CKD, with a focus on its deleterious effects and a description of the clinical management of hyperphosphatemia in a more global setting of CKD-MBD. [ABSTRACT FROM AUTHOR]

Background: COVID-19 was declared a global health emergency. Since children are less than 1% of reported cases, there is limited information to develop evidence-based practice recommendations. The objective of this study was to rapidly gather expert knowledge and experience to guide the care of children with chronic kidney disease during the COVID-19 pandemic. Methods: A four-round multi-center Delphi exercise was conducted among 13 centers in 11 European countries of the European Pediatric Dialysis Working Group (EPDWG) between March, 16th and 20th 2020. Results were analyzed using a mixed methods qualitative approach and descriptive statistics. Results: Thirteen COVID-19 specific topics of particular need for guidance were identified. Main themes encompassed testing strategies and results (n = 4), changes in use of current therapeutics (n = 3), preventive measurements of transmission and management of COVID-19 (n = 3), and changes in standard clinical care (n = 3). Patterns of center-specific responses varied according to regulations and to availability of guidelines. Conclusions: As limited quantitative evidence is available in real time during the rapid spread of the COVID-19 pandemic, qualitative expert knowledge and experience represent the best evidence available. This Delphi exercise demonstrates that use of mixed methodologies embedded in an established network of experts allowed prompt analysis of pediatric nephrologists' response to COVID-19 during this fast-emerging public health crisis. Such rapid sharing of knowledge and local practices is essential to timely and optimal guidance for medical management of specific patient groups in multi-country health care systems such as those of Europe and the US. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is frequent in pediatric nephrology. The 2017 European guidelines recommend keeping 25OH vitamin D (25-D) levels within the 75-120 nmol/L range, ideally with daily supplementation. Intermittent supplementation with D3 has also been proposed. We aimed to assess the influence of our local protocol of intermittent vitamin D supplementation on the evolution of 25-D levels between baseline and 2 months. VITATOL is a prospective single-center study performed in our tertiary unit in children and teenagers followed for chronic kidney disease (CKD), kidney transplantation, or stable chronic nephrotic syndrome with 25-D levels below 75 nmol/L. Intermittent oral cholecalciferol (100,000 IU) was administered depending on baseline vitamin D levels and body weight. The primary outcome was the change in 25-D levels between baseline and 2 months. Secondary outcomes were the evolution of the main mineral biomarkers. Thirty-seven patients were included. Two months after beginning supplementation, corresponding to a median(min-max) of 46 (14-79) days after the last dose of vitamin D, 25-D levels increased from 50 to 76 nmol/L (p < 0.001), 18 patients having 25-D levels within the target range and 2 above. All patients displayed 25-D levels above 50 nmol/L. There were no significant changes in phosphate, PTH, alkaline phosphatase, and FGF23 levels before and after supplementation. Calcium levels increased from 2.39 to 2.44 mmol/L (p = 0.017), but no differences in calciuria and urinary calcium/creatinine ratio were observed.Conclusion: This vitamin D supplementation protocol using intermittent moderate doses of cholecalciferol seems efficient in 54% of cases, with neither significant overdose nor hypercalciuria. What is Known: • Vitamin D deficiency is frequent in pediatric nephrology. • The 2017 European guidelines recommend keeping 25OH vitamin D levels within the 75-120 nmol/L range ideally with daily supplementation, but intermittent supplementation with D3 has also been proposed. What is New: • We assessed the influence of a local protocol of intermittent vitamin D supplementation on the evolution of 25-D levels between baseline and 2 months in children and teenagers followed in pediatric nephrology. • The intermittent cholecalciferol supplementation protocol seems efficient in 54% of cases, with neither significant overdose nor hypercalciuria. [ABSTRACT FROM AUTHOR]

Objective: Mineral and bone disorders associated to chronic kidney disease (CKD-MBD) are a daily challenge for pediatric nephrologists, with a significant risk of long-term bone and vascular comorbidities.Methods: This single-center study is a prospective transversal evaluation of pediatric CKD patients of our center, part of the European 4C study. In addition to clinical and biochemical data, vascular and bone evaluation was performed: 24-h blood pressure assessment, carotid intima-media thickness (cIMT), pulse wave velocity (PWV), and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the ultra-distal tibia. Results are presented as median (range).Results: At a median age of 12.9 years (10.2-17.9), SDS height of − 1.0 (− 3.3-1.2) and estimated glomerular filtration rate (eGFR) of 33 mL/min/1.73m2 (11-72), 32 patients (8 girls) were evaluated. Median calcium, phosphate, parathyroid hormone (PTH), and 25 OHD3 levels were 2.44 mmol/L (2.24-2.78), 1.43 mmol/L (1.0-2.7), 80 pg/mL (9-359), and 70 nmol/L (32-116), respectively. Bivariate Spearman and backward multivariable analyses showed that calcium and bone trabecular thickness (Tb.Th), were positively associated with diastolic and mean arterial blood pressure (both for the 24 h, day and night assessment), whereas PTH and vitamin D did not predict blood pressure.Conclusions: We show that the greater the serum levels of calcium, the greater the (diastolic and mean) blood pressure; moreover, the greater the Tb. Th, the greater the (diastolic and mean) blood pressure. The role of calcium supplements to explain such findings in early pediatric CKD can be discussed. [ABSTRACT FROM AUTHOR]

Background: Post-transplant diabetes mellitus (PTDM) is a major complication of immunosuppressive therapy, with many risk factors reported in adults with renal transplantation. The objective of this study was to investigate potential non-genetic and genetic risk factors of PTDM in children with renal transplantation treated with tacrolimus.Methods: A national database was screened for patients developing PTDM within 4 years following tacrolimus introduction. PTDM was defined as glucose disorder requiring anti-diabetic treatment. PTDM patients were matched to “non-PTDM” control transplanted children according to age, gender, and duration of post-transplant follow-up. Patients were genotyped for six selected genetic variants in POR*28 (rs1057868), PPARa (rs4253728), CYP3A5 (rs776746), VDR (rs2228570 and rs731236), and ABCB1 (rs1045642) genes, implicated in glucose homeostasis and tacrolimus disposition.Results: Among the 98 children with renal transplantation enrolled in this multicentre study, 18 developed PTDM. None of the clinical and biological parameters was significant between PTDM and control patients. Homozygous carriers of POR*28 or wild-type ABCB1 (rs1045642) gene variants were more frequent in PTDM than in control patients with differences close to significance (p = 0.114 and p = 0.066 respectively). A genetic score based on these variants demonstrated that POR*28/*28 and ABCB1 CC or CT genotype carriers were at a significantly higher risk of developing PTDM after renal transplantation.Conclusion: Identification of PTDM risk factors should allow clinicians to allocate the best immunosuppressant for each patient with renal transplantation, and improve care for patients who are at a higher risk. [ABSTRACT FROM AUTHOR]

Background: Childhood-onset systemic lupus erythematosus (cSLE) is rare, and considered more severe than its adult-onset counterpart. Lupus nephritis (LN) occurs more frequently in children, accounting for higher long-term morbidity and mortality compared with adults. Thus, reliable biological markers are needed to predict disease course. This study aimed to investigate the capacity of anti-C1q autoantibodies (Abs) to predict renal flare and global disease activity in cSLE patients, and association with disease activity and kidney involvement. Methods: Twenty-eight patients with cSLE including 19 patients (68%) with a history of LN were included retrospectively. Anti-C1q Abs were analysed by ELISA at renal flare-up or in the quiescent phase of disease and compared with Farr dsDNA assay. Results: Thirty-one flares occurred during follow-up: anti-C1q Abs were positive in 26 (84%), strongly associated with active disease status ( p < 0.0001), and correlated with global disease activity score ( p < 0.0001) and anti-dsDNA Abs presence ( p < 0.0001). The specificity of anti-C1q Abs was higher than anti-dsDNA (73% vs 19%) in discriminating LN patients, whereas the receiver operating characteristic curves were not statistically different (0.83 ± 0.06 vs 0.78 ± 0.08 respectively), similar to C3 dosage. The presence of anti-C1q Abs at diagnosis was not predictive for global or renal flare. Introduction of a modified SLEDAI score excluding dsDNA Abs, demonstrated a stronger correlation of anti-C1q Abs titres with SLEDAI score in comparison with the Farr test. Conclusion: Anti-C1q Abs seem very specific to flares, including LN in children, and their role in daily practice compared with the Farr dsDNA assay needs to be defined. [ABSTRACT FROM AUTHOR]

Background: Peritoneal dialysis (PD) remains the modality of choice in children, but there is no clear evidence to support a better outcome in children treated with PD. We aimed to assess factors that have an impact on the choice of dialysis modality in children and young adults in France and sought to determine the roles of medical factors and center practices. Methods: We included all patients aged <20 years at the start of renal replacement therapy (RRT), recorded in the French RRT Registry between 2002 and 2013. Hierarchical logistic regression models were used to study the association between the patient/center characteristics and the probability of receiving PD as the first dialysis modality. Results: We included 806 patients starting RRT in 177 centers, 23 of which were specialized pediatric centers. Six hundred and one patients (74.6 %) started with hemodialysis (HD), whereas 205 (25.4 %) started with PD. A greater probability of PD was found in younger children, whereas starting the treatment in an emergency setting was associated with a low use of PD. We found a significant variability among centers that accounted for 43 % of the total variability. The probability of PD was higher in adult centers and was proportional to the rate of PD in the center. Conclusions: Center practices are a major factor in the choice of dialysis modality. This raises concerns about patient and family choices and to what extent doctors may influence the final decision. Further pediatric studies focusing on children's and parents' wishes are needed to provide care as close as possible to patients' and families' expectations. [ABSTRACT FROM AUTHOR]

Unlabelled: Determination of plasma creatinine (Pcr) should be associated to an estimation of glomerular filtration rate (eGFR). Pottel et al. established a height-independent equation, eGFR = 107.3/(Pcr/Q) where Q is the median of Pcr (Pottel-Belgium). The aims were to 1) determine a local height-independent equation (Pottel-Lyon), 2) evaluate the performance of these equations compared to the Schwartz 2009 and Schwartz-Lyon equations, and 3) evaluate the height-independent equations in laboratory routine. Therefore, 1) all first pediatric Pcr determination (December 2009-June 2011) were collected, and median of Pcr was determined for each 1-year age interval (Q-Lyon), 2) GFR was measured (mGFR) in 359 children (438 measures) and compared to eGFR, and 3) all first Pcr determination (January 2012-June 2013) were used to calculate eGFR with the Pottel-Lyon and the Pottel-Belgium equations. Pcr was determined by an IDMS-standardized enzymatic assay. In the population with a mGFR, the Pottel-Lyon and the Schwartz-Lyon showed the best performance (bias, P10 and P30). However, the performance in identifying patients with a mGFR < 75 mL/min/1.73 m(2) was similar for all the studied equations.Conclusion: The performance of the height-independent and dependent equations to identify mild renal dysfunction is similar. The height-independent Pottel equation could be proposed as an excellent screening tool for kidney disease when height information is not available. "What Is Known: " • Determination of plasma creatinine in children is rarely associated to an estimation of glomerular filtration rate due to the lack of height information. • Pottel et al. developed a height-independent equation (eGFR = 107.3/(Pcr/Q) where Q is the median of Pcr for each age class. "What Is New: " • The performance of the height-independent (Pottel) or height-dependent (Schwartz) equations is similar to identify renal dysfunction (GFR < 75 mL/min/1.73 m (2) ) in children. • The height-independent Pottel equation could be an excellent screening tool for kidney disease in a general pediatric laboratory when height information is not available. [ABSTRACT FROM AUTHOR]

Background: The management of tubulopathies after renal transplantation (RTx) may require high doses of sodium and bicarbonate, reducing the quality of life and therapeutic compliance of the patient. Some studies on adult patients have highlighted the benefits of fludrocortisone (fludro) in the treatment of severe tubulopathies. Methods: This study was a retrospective review of the medical charts of 15 children, aged 12.4 (range 3.6-17.4) years who received fludro after RTx. Results: With the administration of fludro, both sodium bicarbonate and chloride supplementation decreased, from 10 (range 0-14) to 0 (0-5) g/day, and from 9 (0-20) to 0 (0-3) g/day, respectively (both p < 0.001). Serum potassium also significantly decreased (4.6 ± 0.4 vs. 3.3 ± 0.6 mmol/L; p < 0.001), but there was no significant effect on renal function. Both systolic and diastolic blood pressure increased significantly. Fludro therapy was stopped in six patients due to side-effects (arterial hypertension, hypokalemia during acute diarrhea, gastric pain, n = 3), parental decision ( n = 1), inefficacy and/or non-compliance ( n = 1) and scheduled withdrawal ( n = 1). Four of these patient had subsequent increasing requirements for bicarbonate and/or sodium supplementation, which ultimately required the re-introduction of fludro in two of these patients. Conclusions: Based on our findings, fludro would appear to be an effective therapy in most cases of severe tubulopathy after RTx. Further prospective studies are required to validate this indication and to determine the optimal dose and timing of treatment to avoid side-effects as well as the clinical and biological follow-up. [ABSTRACT FROM AUTHOR]

Background: C3 glomerulopathy (C3G) is characterized by predominant C3 deposits in glomeruli and dysregulation of the alternative pathway of complement. Half of C3G patients have a C3 nephritic factor (C3NeF). C3G incorporated entities with a range of features on microscopy including dense deposit diseases (DDD) and C3 glomerulonephritis (C3GN). The aim of this work was to study children cases of C3G associated with C3NeF. Methods: We reviewed 18 cases of C3G with a childhood onset associated with C3NeF without identified mutations in CFH, CFI, and MCP genes. Results: Clinical histories started with recurrent hematuria for seven patients, nephrotic syndrome for four, acute post-infectious glomerulonephritis for three and acute renal failure for four. Twelve patients had a low C3 at first investigation. Kidney biopsy showed ten C3GN and eight DDD. Twenty-three percent of the patients tested presented elevated sC5b9. Seven patients relapsed 3 to 6 years after the onset. At the end of follow-up, two patients were under dialysis, 11 had a persistent proteinuria, five had none; four patients did not follow any treatment. Steroids were first used in 80 % of cases. Conclusions: C3NeF associated C3G has a heterogeneous presentation and outcome. Anti-proteinuric agents may control the disease during follow-up, even after nephrotic syndrome at the onset. The efficiency of immunosuppressive therapy remains questionable. [ABSTRACT FROM AUTHOR]

Background: Deferasirox (DFX) is an oral iron chelator with an established dose-dependent efficacy in transfusion-related iron overload. Whereas emerging long-term data confirm the safety of the drug, with transient moderate elevation of serum creatinine level, several authors have reported renal tubular dysfunction. The aim of this study was to evaluate tubular and glomerular function before and after the initiation of DFX therapy in a pediatric patient population. Methods: Ten children (4 girls, mean age 12.4 ± 3.9 years) enrolled in a routine blood transfusion program were treated with 24.8 ± 9.6 mg/kg per day of DFX, and renal function was assessed before and 17.2 ± 8.9 months after the initiation of DFX therapy. Results: Prior to treatment with DFX, all patients had a normal glomerular function rate (GFR) (125 ± 15 ml/min per 1.73 m) and normal tubular function. Following the initiation of DFX therapy, the GFR decreased by approximately 20 % with one patient with a GFR of <80 mL/min per 1.73 m and seven patients with a GFR of <100 mL/min per 1.73 m. Two patients experienced a generalized proximal tubular dysfunction whereas nine patients presented at least one sign of proximal tubular dysfunction. Conclusions: Renal toxicity is a frequent adverse event of DFX treatment, presenting as both glomerular and proximal dysfunction. A routine renal assessment is therefore required to prevent chronic kidney disease that may result from prolonged tubular injury. [ABSTRACT FROM AUTHOR]

Background: Autosomal dominant polycystic kidney disease (ADPKD) in children is often regarded as a benign condition. However, previous studies pointed out renal-related anomalies which may benefit from early appropriate treatments. This study was conducted to evaluate the prevalence and severity of early renal dysfunction in ADPKD children. Methods: An extensive renal evaluation was performed in 52 consecutive ADPKD patients diagnosed either from prenatal screening or post-natal ultrasound (US) examination (54 % males, mean age 10 ± 4 years [1-17]). Results: Three patients had both systolic (SBP) and diastolic (DBP) blood pressure above the 95th percentile, one patient had a 'high normal' DBP, and one child was treated with an angiotensin-converting enzyme inhibitor (ACEI). The mean ± SD glomerular filtration rate (GFR ml/min per 1.73 m, inulin clearance) was 115 ± 26 [47-168] but six children (12 %) had a GFR < 90 and 11 (21 %) experienced hyperfiltration (GFR > 135). Microalbuminuria (2 < Ualb/Ucr≤20mg/mmol) was found in 25 patients and five had macroalbuminuria (>20 mg/mmol). Conclusions: Early renal manifestations are frequent in ADPKD children, including hypertension in 6 %, albuminuria in 58 %, and decreased GFR in 12 %. In conclusion, renal function in children with ADPKD should be regularly assessed in order to manage early renal dysfunction and even consider further therapeutic intervention. [ABSTRACT FROM AUTHOR]

Bone damage in children with chronic kidney disease (CKD) is a challenge for pediatric nephrologists. Areal measurements of bone mineral density (BMD) by dual x-ray absorptiometry (DXA) have been routinely performed to assess bone mass but recent international guidelines have concluded that DXA was of less value in CKD. The aim of this study is to evaluate bone quality in CKD children using new bone imaging techniques in a pilot cross-sectional single-center study. We performed bone imaging (high-resolution peripheral quantitative computed tomography, HR-pQCT, XtremeCT, Scanco Medical AG, Switzerland), to assess compartmental volumetric BMD and trabecular microarchitecture in 22 CKD children and 19 controls. In seven younger patients (i.e., under 10 years of age), we performed bone texture analysis (BMA, D3A Medical Systems, France) in comparison to 15 healthy prepubertal controls. Among older children, CKD patients had significantly lower height and body weight without significant impairment of BMD and microarchitecture than healthy controls. In univariate analysis, there were significant correlations between cortical BMD and glomerular filtration rate ( r = -0.46), age ( r = 0.60) and body mass index ( r = 0.67). In younger children, bone texture parameters were not different between patients and controls. Our results did not show significant differences between healthy controls and CKD children for compartmental bone densities and microarchitecture, but the small sample size and the heterogeneity of the CKD group require caution in the interpretation. Novel bone imaging techniques seem feasible in children, and further longitudinal studies are required to thoroughly explore long-term cardiovascular and bone consequences of phosphate-calcium metabolism deregulation during CKD. [ABSTRACT FROM AUTHOR]

McKusick type metaphyseal chondrodysplasia, or cartilage hair hypoplasia (CHH), is a rare autosomal recessive osteochondrodysplasia secondary to a mutation in the RMRP gene. In addition to the metaphyseal chondrodysplasia and the short-limb dwarfism, patients may present with a multisystemic disease, associating immune deficiency with recurrent infantile or childhood infections, hematological abnormalities, and gastrointestinal dysfunction. The probability of malignancy is increased in these patients, as are disimmune manifestations. We report on a 12-year-old girl with a new mutation of the RMRP gene and a severe multisystemic CHH (hematological and pulmonary lesions, severe immune deficiency, arthritis, pancreatic insufficiency, malabsorption, chronic diarrhea) receiving parenteral nutrition who presented with acute symptomatic hypocalcemia and hypercalciuria associated with the presence of autoantibodies directed against the calcium-sensor receptor. At the same time, there was an important escalation of diarrhea. Corticosteroids led to a progressive improvement of biological signs (hypocalcemia, hypoparathyroidism). By contrast, gastrointestinal symptoms and malabsorption did not improve. To our knowledge, this is the first report of autoimmune hypoparathyroidism in CHH. [ABSTRACT FROM AUTHOR]

Human herpesvirus 6 (HHV-6) infection can induce unusual complications in transplant patients, such as interstitial pneumonitis, encephalitis and marrow aplasia. We describe the clinical course of HHV-6 infection in a girl with renal transplantation. She presented with diarrhea and poor feeding on day 36 post-transplantation (Tx), after a 5-day steroid pulse for clinical signs of acute rejection. A week later she developed fever and had elevated plasma creatinine and lactic dehydrogenase levels, but a physical examination did not reveal any anomalies with respect to suggest rash, pneumonitis, encephalitis or lymphadenopathy. Two weeks later, the patient developed anemia and leucopenia. HHV-6 was the only pathogen detected by the PCR assay of the serum and marrow aspiration. The patient had a successful recovery without specific treatment. This case report highlights the wide spectrum of complications resulting from HHV-6 infection in immunosuppressed patients. [ABSTRACT FROM AUTHOR]

Renal transplantation (Tx) is the treatment of choice for end-stage renal disease. The incidence of acute rejection after renal Tx has decreased because of improving early immunosuppression, but the risk of disease recurrence (DR) is becoming relatively high, with a greater prevalence in children than in adults, thereby increasing patient morbidity, graft loss (GL) and, sometimes, mortality rate. The current overall graft loss to DR is 7–8%, mainly due to primary glomerulonephritis (70–80%) and inherited metabolic diseases. The more typical presentation is a recurrence of the full disease, either with a high risk of GL (focal and segmental glomerulosclerosis 14–50% DR, 40–60% GL; atypical haemolytic uraemic syndrome 20–80% DR, 10–83% GL; membranoproliferative glomerulonephritis 30–100% DR, 17–61% GL; membranous nephropathy ∼30% DR, ∼50% GL; lipoprotein glomerulopathy ∼100% DR and GL; primary hyperoxaluria type 1 80–100% DR and GL) or with a low risk of GL [immunoglobulin (Ig)A nephropathy 36–60% DR, 7–10% GL; systemic lupus erythematosus 0–30% DR, 0–5% GL; anti-neutrophilic cytoplasmic antibody (ANCA)-associated glomerulonephritis]. Recurrence may also occur with a delayed risk of GL, such as insulin-dependent diabetes mellitus, sickle cell disease, endemic nephropathy, and sarcoidosis. In other primary diseases, the post-Tx course may be complicated by specific events that are different from overt recurrence: proteinuria or cancer in some genetic forms of nephrotic syndrome, anti-glomerular basement membrane antibodies-associated glomerulonephritis (Alport syndrome, Goodpasture syndrome), and graft involvement as a consequence of lower urinary tract abnormality or human immunodeficiency virus (HIV) nephropathy. Some other post-Tx conditions may mimic recurrence, such as de novo membranous glomerulonephritis, IgA nephropathy, microangiopathy, or isolated specific deposits (cystinosis, Fabry disease). Adequate strategies should therefore be added to kidney Tx, such as donor selection, associated liver Tx, plasmatherapy, specific immunosuppression protocols. In such conditions, very few patients may be excluded from kidney Tx only because of a major risk of DR and repeated GL. In the near future the issue of DR after kidney Tx may benefit from alternatives to organ Tx, such as recombinant proteins, specific monoclonal antibodies, cell/gene therapy, and chaperone molecules. [ABSTRACT FROM AUTHOR]

Long-term outcome of idiopathic steroid-resistant nephrotic syndrome was retrospectively studied in 78 children in eight centers for the past 20 years. Median age at onset was 4.4 years (1.1–15.0 years) and the gender ratio was 1.4. Median follow-up period was 7.7 years (1.0–19.7 years). The disease in 45 patients (58%) was initially not steroid-responsive and in 33 (42%) it was later non-responsive. The main therapeutic strategies included administration of ciclosporine (CsA) alone ( n = 29; 37%) and CsA + mycophenolate mofetil ( n = 18; 23%). Actuarial patient survival rate after 15 years was 97%. Renal survival rate after 5 years, 10 years and 15 years was 75%, 58% and 53%, respectively. An age at onset of nephrotic syndrome (NS) > 10 years was the only independent predictor of end-stage renal disease (ESRD) in a multivariate analysis using a Cox regression model ( P < 0.001). Twenty patients (26%) received transplants; ten showed recurrence of the NS: seven within 2 days, one within 2 weeks, and two within 3–5 months. Seven patients lost their grafts, four from recurrence. Owing to better management, kidney survival in idiopathic steroid-resistant nephrotic syndrome (SRNS) has improved during the past 20 years. Further prospective controlled trials will delineate the potential benefit of new immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

Studies have suggested involvement of interleukin 17 (IL-17) in autoimmune diseases, although its effect on B cell biology has not been clearly established. Here we demonstrate that IL-17 alone or in combination with B cell–activating factor controlled the survival and proliferation of human B cells and their differentiation into immunoglobulin-secreting cells. This effect was mediated mainly through the nuclear factor-κB-regulated transcription factor Twist-1. In support of the relevance of our observations and the potential involvement of IL-17 in B cell biology, we found that the serum of patients with systemic lupus erythematosus had higher concentrations of IL-17 than did the serum of healthy people and that IL-17 abundance correlated with the disease severity of systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]

We report on a case of hepatitis B virus-related polyarteritis nodosa (PAN) in a 4-year-old Turkish boy who was first admitted because of severe arterial hypertension. The diagnosis of PAN was provided by conventional renal arteriography and the child was successfully treated with intensive sequential therapy combining short-term prednisone, plasma exchange and interferon-α-2b. Nine years later, he had no sign of PAN, normal blood pressure and normal renal function in the absence of any treatment. [ABSTRACT FROM AUTHOR]

The occurrence of membranous nephropathy in pediatric series of systemic lupus erythematosus has been reported only rarely, probably due to a very low frequency. One hundred fifty-four children who were seen in 100 French pediatric centers between January 2002 and April 2005 were included. Fifteen (12 girls and three boys) out of the 81 (18.5 %) children with renal involvement presented histological features of membranous nephropathy. Their ages ranged from six to 15 years old (mean=11.3) at the age of SLE diagnosis and 8/15 children were of African origin. Isolated membranous nephropathy was observed in nine patients, of whom five patients displayed a complete recovery following immunosuppressive treatment. Associated proliferative lesions were observed on the first kidney specimen in two patients and in a further renal biopsy in four other patients, leading to a less favorable course of lupus nephropathy. [ABSTRACT FROM AUTHOR]

Primary hyperoxaluria type 1, the most common form of primary hyperoxaluria, is an autosomal recessive disorder caused by a deficiency of the liver-specific enzyme alanine: glyoxylate aminotransferase (AGT). This results in increased synthesis and subsequent urinary excretion of the metabolic end product oxalate and the deposition of insoluble calcium oxalate in the kidney and urinary tract. As glomerular filtration rate (GFR) decreases due to progressive renal involvement, oxalate accumulates and results in systemic oxalosis. Diagnosis is still often delayed. It may be established on the basis of clinical and sonographic findings, urinary oxalate ± glycolate assessment, DNA analysis and, sometimes, direct AGT activity measurement in liver biopsy tissue. The initiation of conservative measures, based on hydration, citrate and/or phosphate, and pyridoxine, in responsive cases at an early stage to minimize oxalate crystal formation will help to maintain renal function in compliant subjects. Patients with established urolithiasis may benefit from extracorporeal shock-wave lithotripsy and/or JJ stent insertion. Correction of the enzyme defect by liver transplantation should be planned, before systemic oxalosis develops, to optimize outcomes and may be either sequential (biochemical benefit) or simultaneous (immunological benefit) liver–kidney transplantation, depending on facilities and access to cadaveric or living donors. Aggressive dialysis therapies are required to avoid progressive oxalate deposition in established end-stage renal disease (ESRD), and minimization of the time on dialysis will improve both the patient’s quality of life and survival. [ABSTRACT FROM AUTHOR]

To outline the specific oral surveillance needs of renal transplant children, we report the 4-year follow-up data of 106 children examined routinely on a 6-month basis and upon request from the medical team or the parents in the interval. Data were recorded for hard and soft dental tissues, including enamel defects carious lesions, gingival status, orthodontic treatment needs, and wisdom teeth eruption. Hard-tissue lesions were noted in 34.9% of the children, caries lesions on the permanent teeth were seen in 15.0% of cases, 18.86% of the patients had orthodontic treatment. Spontaneous examination, upon request for medical reasons, was given for 26 children. Twenty-one demands originated from the parents. Over a 4-year period the attendance of a dental specialist resulted in a significant improvement in the oral health of the renal transplant children. [ABSTRACT FROM AUTHOR]

Noncompliance is frequent in children and adolescents with nephrotic syndrome. Once suspected, noncompliance is difficult to confirm and often impossible to avoid. The standard oral glucocorticoid treatment for children has been shown to be efficient and safe. However, a small number of children/parents are noncompliant to the steroid treatment, resulting in multiple relapses. For these patients the use of steroids with prolonged half-life such as triamcinolone acetonide (TA) can be helpful. We studied seven children (six boys, one girl; median age at diagnosis 8.6 years, range 1.8–10.7) receiving conventional steroid treatment for a median of 30 months (8−74) before starting intramuscular (IM) TA treatment. The standard prednisone treatment was replaced by 1 monthly IM injection of TA (1 mg/kg per day oral prednisone replaced by 1 mg/kg per month IM TA). The treatment was tapered off by a reduction of 10–20% of the initial dose per month over 6–8 months. After a mean observation period of 14 months (3–36) the results were evaluated in terms of number of relapses and treatment tolerance. Four children showed a clear decrease in number of relapses (1.8 to 0 per year); in the other three the number of relapses remained stable. Tolerance was excellent (no cataract, no arterial hypertension), and the cushingoid syndrome did not exceed the level experienced under conventional oral steroid therapy. However, growth velocity decreased during the TA treatment and returned to normal after discontinuation of TA. These preliminary results demonstrate that TA may be used in patients of suspected noncompliance in steroid-sensitive patients who respond with a complete remission during TA treatment over the observation period. Patients who do not benefit from the TA can be classified as very probably steroid-dependent. TA seems to be a useful therapeutic strategy in those patients for whom noncompliance is strongly suspected. [ABSTRACT FROM AUTHOR]

Nephrotoxicity is a well-known adverse effect of cyclosporine A (CyA) treatment in children with steroid-dependent (SD) and steroid-resistant (SR) nephrotic syndrome (NS). We analyzed nine children (age: 3.3-15.7 years, two girls) with SD or SR NS who experienced a significant decrease in their GFR under CyA treatment as measured by inulin clearance (CIN). Mycophenolate mofetil (MMF) was introduced progressively until doses of 1 g/1.73 m2 twice daily were reached. CyA treatment was stopped after introduction of MMF and oral steroids were reduced if possible. After a median follow up of 261 days, no adverse effects of MMF such as diarrhea or hematological anomalies occurred in our patients. After switching from CyA to MMF, those children with SD NS remained in remission without proteinuria and those with SR NS did not show any significant changes in their residual proteinuria. The serum protein level did not change significantly in any of the children analyzed. GFR increased from a mean of 76.9±4.8 to 119.9±5.9 mL/1.73 m2 per min (P<0.001). Oral steroid treatment could be reduced from a median [range] prednisone dose of 0.85 [0.26-2.94] mg/kg/d pre-MMF to 0.29 [0-1.1] mg/kg per day (P=0.026), and blood pressure decreased moderately after CyA withdrawal, but the difference did not reach statistical significance. We conclude that a switch from CyA to MMF seems to be safe for children with SDNS and SRNS in terms of side effects as well as disease control, at least in the short term. Interruption of CyA treatment lead to rapid amelioration of kidney function in these children, often associated with steroid sparing, which may lead to additional benefit for growth velocity, blood pressure and physical appearance. [ABSTRACT FROM AUTHOR]

Children with chronic kidney disease suffer from excessive cardiovascular mortality and early alterations of the cardiovascular system. Tissue doppler imaging is a validated echocardiographic tool to assess early systolic and diastolic cardiac dysfunction. We hypothesized that tissue Doppler velocities would reveal reduced cardiac function in children with chronic kidney disease compared to healthy children. A standardized echocardiographic exam was performed in 128 patients of the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) Study aged 6–17 years with an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2. Tissue Doppler measurements included early (E') and late (A') diastolic and systolic (S') velocity at the mitral and septal annulus of the left ventricle. Measured values were normalized to z-scores using published reference data. Predictors of E'/A', E/E', S' and left ventricular mass index (LVMI) were assessed by multiple linear regression analyses. Tissue Doppler E' was reduced and tissue Doppler A' increased, resulting in a reduced tissue Doppler E'/A' ratio (z-score −0.14, p < 0.0001) indicating reduced diastolic function compared to healthy children. Reduced tissue Doppler E'/A' Z-Scores were independently associated with lower eGFR (p = 0.002) and increased systolic blood pressure (p = 0.02). While E/E' Z-Scores were increased (Z-score 0.57, p < 0.0001), patients treated with pharmacological RAS blockade but not with other antihypertensive treatments had significantly lower E/E' and higher E'/A' Z-Scores. Systolic tissue Doppler velocities were significantly decreased (Z-score −0.24, p = 0.001) and inversely correlated with E/E' Z-Scores (r = −0.41, p < 0.0001). LVMI was not associated with systolic or diastolic tissue Doppler velocities. Concentric left ventricular hypertrophy showed a tendency to lower S' in multivariate analysis (p = 0.13) but no association to diastolic function. Concentric left ventricular geometry was significantly associated with lower midwall fractional shortening. In summary, systolic and diastolic function assessed by tissue Doppler is impaired. eGFR, systolic blood pressure and the type of antihypertensive medications are significant predictors of diastolic function in children with CKD. Left ventricular morphology is largely independent of tissue Doppler velocities. Tissue Doppler velocities provide sensitive information about early left ventricular dysfunction in this population. [ABSTRACT FROM AUTHOR]

While children approaching end-stage kidney disease (ESKD) are considered at risk of uremic anorexia and underweight they are also exposed to the global obesity epidemic. We sought to investigate the variation of nutritional status in children undergoing chronic peritoneal dialysis (CPD) around the globe. The distribution and course of body mass index (BMI) standard deviation score over time was examined prospectively in 1001 children and adolescents from 35 countries starting CPD who were followed in the International Pediatric PD Network (IPPN) Registry. The overall prevalence of underweight, and overweight/obesity at start of CPD was 8.9% and 19.7%, respectively. Underweight was most prevalent in South and Southeast Asia (20%), Central Europe (16.7%) and Turkey (15.2%), whereas overweight and obesity were most common in the Middle East (40%) and the US (33%). BMI SDS at PD initiation was associated positively with current eGFR and gastrostomy feeding prior to PD start. Over the course of PD BMI SDS tended to increase on CPD in underweight and normal weight children, whereas it decreased in initially overweight patients. In infancy, mortality risk was amplified by obesity, whereas in older children mortality was markedly increased in association with underweight. Both underweight and overweight are prevalent in pediatric ESKD, with the prevalence varying across the globe. Late dialysis start is associated with underweight, while enteral feeding can lead to obesity. Nutritional abnormalities tend to attenuate with time on dialysis. Mortality risk appears increased with obesity in infants and with underweight in older children. [ABSTRACT FROM AUTHOR]

About 90% of cases of hemorrhagic uremic syndrome (HUS) occur in early childhood and most frequently are preceded by bloody diarrhea due to shiga-like toxin (SLT) producing Escherichia coli. We report a case of a newborn girl presenting with bloody diarrhea on her 7th day of life. Acute renal failure, severe arterial hypertension and hemolytic anemia were detected and prompt peritoneal dialysis and antihypertensive therapy were required. The girl had several episodes of seizures, necessitating intravenous phenobarbital. Transfontanel ultrasonography 48 h after disease onset was normal, whereas, MRI investigation 10 days later revealed severe ischemic lesions with beginning cystic encephalopathy. Renal function recovered and only very moderate tubular dysfunction remained. Serum analysis of factor H, von Willebrand factor protease, homocystinemia, proteins C and S, and antithrombin III were all normal. Mutation analysis of factor V Leiden, factor II, and methyltetrahydrofolate-reductase were normal. E. coli 0157:H7 and SLT 2 were detected in the stool. SLT 2 was also found in the mother’s stool. This is the first report of mother-to-child transmission of SLT-producing E. coli. [ABSTRACT FROM AUTHOR]