Vitamin D and calcium intakes in general pediatric populations: A French expert consensus paper.

OBJECTIVES: Nutritional vitamin D supplements are often used in general pediatrics. Here, the aim is to address vitamin D supplementation and calcium nutritional intakes in newborns, infants, children, and adolescents to prevent vitamin D deficiency and rickets in general populations. STUDY DESIGN: We formulated clinical questions relating to the following categories: the Patient (or Population) to whom the recommendation will apply; the Intervention being considered; the Comparison (which may be "no action," placebo, or an alternative intervention); and the Outcomes affected by the intervention (PICO). These PICO elements were arranged into the questions to be addressed in the literature searches. Each PICO question then formed the basis for a statement. The population covered consisted of children aged between 0 and 18 years and premature babies hospitalized in neonatology. Two groups were assembled: a core working group and a voting panel from different scientific pediatric committees from the French Society of Pediatrics and national scientific societies. RESULTS: We present here 35 clinical practice points (CPPs) for the use of native vitamin D therapy (ergocalciferol, vitamin D2 and cholecalciferol, vitamin D3) and calcium nutritional intakes in general pediatric populations. CONCLUSION: This consensus document was developed to provide guidance to health care professionals on the use of nutritional vitamin D and dietary modalities to achieve the recommended calcium intakes in general pediatric populations. These CPPs will be revised periodically. Research recommendations to study key vitamin D outcome measures in children are also suggested.

[Solitary kidney: Management and outcome]. / Conduite à tenir devant un rein unique.

Solitary functioning kidneys form an important subgroup of congenital anomalies of the kidney and urinary tract (CAKUT). A solitary kidney can be congenital or acquired after unilateral nephrectomy and is often associated with ipsilateral urogenital anomalies. Both types of solitary functioning kidney are associated with an increased risk of chronic kidney disease (CKD). A low functional nephron number results in compensatory glomerular hypertension and enlargement of remnant nephrons, indicating glomerular hyperfiltration. Glomerular hyperfiltration may lead to glomerulosclerosis, which further results in hypertension, proteinuria, and decline of the glomerular filtration rate (GFR) in the long run. About 20-30% of patients with solitary functioning kidney have hypertension, proteinuria, or reduced GFR during childhood, especially those with associated CAKUT. Regular and lifetime monitoring (including growth, blood pressure, serum creatinine, proteinuria or microalbuminuria, and renal ultrasound) is required. The frequency and modality of follow-up should be adapted to individual risk for CKD. Early detection of renal injury and timely nephroprotective measures are critical.

[Diagnosis and management of chronic kidney disease in children: Guidelines of the French Society of Pediatric Nephrology]. / Diagnostic et prise en charge de la maladie rénale chronique de l'enfant : recommandations de la Société de néphrologie pédiatrique (SNP).

These guidelines are intended to assist physicians in the care of children with chronic kidney disease (CKD), defined in children as in adults, regardless of its cause. Often silent for a long time, CKD can evolve to chronic renal failure or end-stage renal disease. Its management aims at slowing disease progression and treating CKD complications as soon as they appear. The different aspects of pediatric CKD care are addressed in these guidelines (screening, treatment, monitoring, diet, quality of life) as proposed by the French Society of Pediatric Nephrology. Highly specialized care provided in the hospital setting by pediatric nephrologists is not detailed.

[Clinical and biochemical characterization of childhood urolithiasis]. / Caractéristiques cliniques et biochimiques des lithiases urinaires de l'enfant.

OBJECTIVES: Urolithiasis is rare in children, but the incidence has increased over the past few decades. This study aims at describing the clinical and biochemical characteristics, etiology, and treatment of urolithiasis in children. METHODS: This was a retrospective study of all children under 16 years of age seen at the Bordeaux University Children's Hospital with a diagnosis of urolithiasis. The diagnosis was confirmed either radiologically or clinically by the expulsion of the stone. RESULTS: A total of 186 children with a diagnosis of urolithiasis between 1994 and 2012 were included. The median age at diagnosis was 7.4 years. The male-to-female ratio was 1.9. The estimated annual incidence was around 5.5/100,000 children under 15 years of age in the past 5 years. The main presenting feature was nonspecific abdominal pain (71%). Metabolic calculi accounted for 48% of the patients with idiopathic hypercalciuria as the main cause. Genetic diseases accounted for 15% of cases. The proportion of infectious calculi was estimated at 33% and decreased in the past two decades. Stone fragments were sent for analysis in 86 children, and calcium oxalate was the major component (37%), followed by calcium phosphate (33%), purine (9%), and struvite (8%). At least 26% of patients experienced recurrence of stone passage. CONCLUSION: This retrospective study highlighted changes in characteristics of pediatric urolithiasis over time. Childhood-onset urolithiasis requires complete etiological work-up so that a metabolic cause with a high risk of recurrence does not go unrecognized.

[Viral epidemiology and clinical severity during the peak of the influenza A(H1N1) variant epidemic in febrile respiratory diseases of children]. / Epidémiologie virale et sévérité clinique pendant le pic d'épidémie grippale A(H1N1) variant dans les atteintes respiratoires fébriles de l'enfant.

UNLABELLED: In 2009, a new emerging flu virus, A(H1N1), was identified. Its true medical impact on children's health remains widely debated. AIM: To define the prevalence of respiratory disease in children hospitalized with fever during the influenza A(H1N1) epidemic and to determine the clinical, paraclinical, and outcome characteristics according to the viruses identified. MATERIAL AND METHODS: Children hospitalized for a febrile respiratory disease were included in this prospective cohort study conducted at Bordeaux University's Children's Hospital (France) during the influenza epidemic from 2009/11/23 to 2009/12/20. RESULTS: Seventy-three children were included in the study. Viruses were identified by PCR in 52% (38/73) of cases, including 23% (17/73) A(H1N1) virus and 29% (21/73) other viruses, 22% (16/73) of which were syncytial respiratory viruses. There was only one case of co-infection between A(H1N1) virus and another virus from the para-influenza virus or adenovirus or bocavirus pool. No significant difference regarding age, sex, or risk factors in the different viral groups was noted. Regarding the A(H1N1) virus, the most frequent symptoms were deterioration of the overall health status, cough, ENT disease, and rapid breathing, with significantly less increased breathing effort and auscultatory abnormality albeit with more seizures. There was no significant difference between groups regarding laboratory data. Management and outcome were similar. CONCLUSION: The prevalence of A(H1N1) virus during the 2009 epidemic in Aquitaine was low among febrile hospitalized children with breathing symptoms. Clinical and paraclinical signs were non-specific. The tolerance and prognosis of influenza A(H1N1) infection in children was satisfactory.

[ESRD in children and adolescents]. / Enfants et adolescents en IRCT.

This chapter provides indicators to describe the specificity of End Stage Renal Disease in children in France and to study these patients'outcome and the choices of treatment modalities. In 2011, the incidence and the prevalence of ESRD among patients under 20 years old remained stable at 8 and 53 pmp respectively. The first causes of ESDR remain uropathies and hypodysplasia followed by glomerulonephritis and genetic diseases. Considering the initial treatment, we found a high rate of hemodialysis and a low rate of peritoneal dialysis that is mainly used in younger children. In 2011, 31 preemptive transplantations were performed accounting for 27.7% of new patients. Finally, survival analysis confirm that younger children (under 4 years old) have the highest risk of death (88% survival rate at 2 years vs. 98% in patients over 4 years old) and that the treatment of choice remains the renal transplantation since it increases the expected remaining lifetime of 20 to 40 years depending on the considered age.

[Secondary hyperoxaluria and nephrocalcinosis due to ethylene glycol poisoning]. / Hyperoxalurie et néphrocalcinose secondaires à une intoxication à l'éthylène glycol.

We report the case of a 3-year-old boy admitted to the pediatric emergency department for ethylene glycol poisoning. During hospitalization, he presented dysuria associated with crystalluria. Blood tests showed metabolic acidosis with an elevated anion gap. A renal ultrasound performed a few weeks later revealed bilateral medullary hyperechogenicity. Urine microscopic analysis showed the presence of weddellite crystals. Secondary nephrocalcinosis due to ethylene glycol intoxication was diagnosed. Hyperhydration and crystallization inhibition by magnesium citrate were initiated. Despite this treatment, persistent weddellite crystals and nephrocalcinosis were seen more than 2years after the intoxication. Ethylene glycol is metabolized in the liver by successive oxidations leading to its final metabolite, oxalic acid. Therefore, metabolic acidosis with an elevated anion gap is usually found following ethylene glycol intoxication. Calcium oxalate crystal deposition may occur in several organs, including the kidneys. The precipitation of calcium oxalate in renal tubules can lead to nephrocalcinosis and acute kidney injury. The long-term renal prognosis is related to chronic tubulointerstitial injury caused by nephrocalcinosis. Treatment of ethylene glycol intoxication is based on specific inhibitors of alcohol dehydrogenase and hemodialysis in the most severe forms, and should be started promptly.

Disparities in policies, practices and rates of pediatric kidney transplantation in Europe.

We aimed to provide an overview of kidney allocation policies related to children and pediatric kidney transplantation (KTx) practices and rates in Europe, and to study factors associated with KTx rates. A survey was distributed among renal registry representatives in 38 European countries. Additional data were obtained from the ESPN/ERA-EDTA and ERA-EDTA registries. Thirty-two countries (84%) responded. The median incidence rate of pediatric KTx was 5.7 (range 0-13.5) per million children (pmc). A median proportion of 17% (interquartile range 2-29) of KTx was performed preemptively, while the median proportion of living donor KTx was 43% (interquartile range 10-52). The median percentage of children on renal replacement therapy (RRT) with a functioning graft was 62%. The level of pediatric prioritization was associated with a decreased waiting time for deceased donor KTx, an increased pediatric KTx rate, and a lower proportion of living donor KTx. The rates of pediatric KTx, distribution of donor source and time on waiting list vary considerably between European countries. The lack of harmonization in kidney allocation to children raises medical and ethical issues. Harmonization of pediatric allocation policies should be prioritized.

[Idiopathic nephrotic syndrome in children: Incidence, clinical presentation, and outcome in the county of Gironde, France]. / Syndrome néphrotique idiopathique de l'enfant : incidence, présentation clinique et devenir dans le département de la Gironde, France.

AIMS: To estimate the incidence and describe the clinical presentation and outcome (steroid responsiveness, clinical course, complications) of idiopathic nephrotic syndrome in children in a population-based retrospective study. METHODS: Using local registries and the hospital discharge diagnosis system from two centers, all new cases of idiopathic nephrotic syndrome were identified in Gironde (France) between January 1992 and May 2008. To estimate incidence, population-based denominators were obtained from the National Institute for Statistics and Economic Studies (INSEE). Clinical data were collected from medical charts. RESULTS: Ninety-nine cases of idiopathic nephrotic syndrome were reported (66 boys, 18 non-Caucasians) with an incidence of 2.3/100,000 (CI, 1.8-3.0) children less than 15 years. Ninety patients (91%) had steroid-sensitive nephrotic syndrome (SSNS) and nine (9%) were steroid-resistant (SRNS). The median time to remission in SSNS was 11 days. Relapses occurred in 75 (83%) children with SSNS with a median of four relapses (range, 1-32). The cumulative relapse-free incidence was 60% at 10 years after diagnosis in SSNS and 13% of patients aged 18 years old or over still had active disease. In SSNS, the only significant factor associated with steroid dependency or use of non steroid drugs was the time to initial response to steroids greater than 14 days. Nineteen children (19%) experienced severe complications of nephrotic syndrome including 11 bacterial infections and two thromboembolic complications. Two children with SRNS, of whom one was initially steroid-responsive, developed end-stage renal failure. CONCLUSION: The incidence and outcome of idiopathic nephrotic syndrome in Gironde are comparable to the rates found in other studies. The disease may have a long course and the time for response to steroids at disease onset is the main predictor of steroid dependency and of use of non steroid agents.

Development of a Bayesian estimator for the therapeutic drug monitoring of mycophenolate mofetil in children with idiopathic nephrotic syndrome.

The use of mycophenolate mofetil (MMF) in children with idiopathic nephrotic syndrome (INS) is increasing. However, the clinical benefit of its monitoring has been scarcely studied, and little is known about its pharmacokinetics in this context. The objectives of the present study were: (i) to study and model the pharmacokinetics of mycophenolic acid (MPA; the active moiety of MMF) in paediatric patients with INS given MMF, at all stages of the disease; (ii) to develop a Bayesian estimator (MAP-BE) for individual inter-dose area under the concentration-time curve (AUC) prediction in this population, using a limited blood sampling strategy (LSS). Full-pharmacokinetic (PK) profiles of MPA collected in paediatric inpatients with INS already treated with a maintenance immunosuppressive therapy based on MMF (with no calcineurin inhibitors; CNI) were studied. A classical iterative two-stage (ITS) method was applied to model the data and develop MAP-BEs using a one-compartment open model where the absorption is described by a double gamma law allowing the description of a potential enterohepatic recirculation. The performance of the MAP-BE developed for individual exposure assessment was evaluated by the bias and precision of predicted AUCs with respect to measured, trapezoidal AUCs (reference value), and by the proportion of predicted AUCs with absolute error >20%. These PK tools were tested in an independent group of patients. Sixty PK profiles of MPA from children receiving MMF in association to corticosteroids or given alone were included in the study. Forty-five of these PK profiles were used to develop a PK model and a MAP-BE, and 15 for their validation. In the building group, the PK model fitted accurately the PK profiles of MPA: mean residual error of modelled vs. reference AUC was m±SD=-0.015±0.092 (range: -0.153 to 0.204). The MAP-BE which allowed the estimation of MPA AUC on the basis of a 20 min-60 min-180 min LSS was then developed. In the independent group of patients, its mean residual error vs. reference AUCs was m±SD=-0.036±0.145 (range: -0.205 to 0.189). Thus, a PK model and its derived MAP-BE for MMF (without any associated CNI) when given to children with INS have been developed. Clinical trials using these PK tools could test the potential impact of the therapeutic drug monitoring of MMF based on the AUC on the clinical evolution of INS.

[Long term renal outcome of children born preterm: a regular follow-up is needed]. / Devenir rénal des enfants nés grands prématurés: un suivi simple mais régulier est nécessaire.

Most of the published studies evaluating renal prognosis of children born very preterm found asymptomatic abnormalities (blood pressure, glomerular filtration rate GFR, hypercalciuria, decreased renal size, microalbuminuria...) during childhood or early adulthood. The objective of this study was to assess renal function (inulin clearance) in a prospective single-center cohort of children born preterm between 1998 and 2001 (< 30 GW,<1000 g) and to identify neonatal risk factors for renal abnormalities during childhood. Fifty children were included in the final part of the study. At a mean age of 7.6 years, no patient had arterial hypertension or chronic kidney disease, but mean centile for diastolic blood pressure was higher than expected and ultrasounds revealed small-sized kidneys compared to controls. The average GFR was 112 ml/min per 1.73 m(2) (91-158). Two children had microalbuminuria, two had hypercalciuria and one had nephrocalcinosis. Children with intra- or extra-uterine growth retardation had an impaired GFR compared to children with appropriate pre- and post-natal growth (107 vs. 110 vs. 125 ml/min per 1.73 m(2), p<0.05). Children with bronchopulmonary dysplasia had a significant higher microalbuminuria. In conclusion, findings of borderline blood pressure and reduced kidney size in children born preterm can be regarded as markers of reduced nephron number. Long term renal follow-up (blood pressure, serum creatinine, urine albumin / creatinine ratio) should be performed in all children born very preterm, with an early referring when abnormalities are highlighted.

De novo malignancy after solid organ transplantation in children.

The aim of this study was to assess the prevalence of de novo malignancy after solid organ transplantation in childhood. A retrospective questionnaire-based survey was sent to 9 referral centers for pediatric organ transplantation in France. Among 1326 children who underwent solid organ transplantation since 1996, 80 (6%) presented with de novo malignancy posttransplantation during childhood: posttransplant lymphoproliferative disease was the most common (5% of pediatric recipients) comprising 80% of all tumors, with a disproportionately high prevalence among combined liver and small bowel recipients (18%). Various solid tumors were observed mainly among kidney recipients. No skin cancer was reported.

[Long-term steroid therapy in children: is adjunct therapy relevant in nephrotic syndrome?]. / Corticothérapie prolongée chez l'enfant : quelle place pour un traitement adjuvant dans le syndrome néphrotique ?

The impact of glucocorticoids on bone is specifically relevant in children exposed to a long course of treatment. Corticosteroids lead to a decrease in bone formation, mainly by osteoblastic inhibition in trabecular bone. They also play an indirect role in bone metabolism through systemic actions, such as bone maturation delay, hypogonadism, pubertal delay, and IGF1 inhibition. A systematic review of the literature was conducted. We found 12 clinical trials of interventions including calcium, vitamin D, growth hormone, calcitonin, and bisphosphonates for preventing bone disease in children receiving steroid therapy. There were few randomized controlled trials (n=7), with a limited number of patients, so that a meta-analysis could not be performed. Calcium and vitamin D supplementation may, however, have a beneficial effect on bone in children with nephrotic syndrome receiving long-term steroid therapy. We, therefore, recommend routine vitamin D supplementation, use of steroid-sparing protocols, and global prevention of risk to bone (adequate calcium intake, sun exposure, and physical activity).