BACKGROUND AND OBJECTIVES:The primary objective of our retrospective, descriptive study was to investigate practices at the University Hospitals of Nîmes and Montpellier regarding antibiotic prophylaxis for patients aged 1 to 3 years with congenital anomalies of the kidney and urinary tract (CAKUT). The secondary objective was to describe the clinical, microbiological, and therapeutic characteristics of this population of children. METHODS:Patients were selected from the hospital records of all children who underwent a cystography at Nîmes and Montpellier University Hospitals between 01/01/2019 and 31/12/2021. RESULTS:Of the 79 patients with Grade 3 or higher vesicoureteral reflux (VUR3+), 86.8 % were treated with antibiotic prophylaxis (93.9 % with sulfamethoxazole-trimethoprim and 6.1 % with cefaclor). Of the 97 patients with other CAKUT, 47.3 % received an antibiotic prophylaxis (84.1 % with sulfamethoxazole-trimethoprim and 15.9 % with cefaclor). The percentages of patients who presented 1 or more febrile UTIs in the VUR3+ group with antibiotic prophylaxis and without prophylaxis were 84.8 % and 90.9 %, respectively. In the VUR3+ group, there was no significant difference between patients with antibiotic prophylaxis or not (p-value = 1) for having at least one episode of febrile UTI. CONCLUSIONS:Based on our observational (real-world) data, there is no evidence for the benefit of antibiotic prophylaxis in children with VUR or other CAKUT.

The objective of this study was to establish a French National Diagnosis and Care Protocol (PNDS: Protocole National de Diagnostic et de Soins), with the aim of providing health professionals with free, open access synthesis on optimal management and care of patients with Infantile Idiopathic Hypercalcemia (IIH) (https://www.has-sante.fr/jcms/p_3522489/fr/hypercalcemie-infantile-idiopathique-hii). The process involved a critical review of the literature and a multidisciplinary expert consensus. IIH is a rare genetic disorder, with a prevalence estimated at 1 in 33,000. Its clinical manifestations (such as urinary stones or nephrocalcinosis) can appear at different ages. The pathophysiology of IHH is characterized by excessive 1,25(OH)2 vitamin D mediated dietary digestive calcium absorption. The underlying mechanism varies depending on the pathogenic variant involved, which is located in one of two genes, CYP24A1 or SLC34A1. The natural history and pathophysiology of IHH remain poorly understood and are underreported in the literature. Management of the disease varies according to the presentation and severity of hypercalcemia. Non-specific management strategies encompass the cessation of calcium intake, the discontinuation of native vitamin D supplementation, hyperhydration, and the occasional utilization of bisphosphonates. The necessity for long-term treatment, which may encompass both non-specific measures and specific interventions, depends on the severity and the genetic variant identified. Long-term follow-up appears essential, although there is limited data available, particularly for detecting complications of the disease, with nephrocalcinosis being the primary one.

Adherence to cysteamine in nephropathic cystinosis (NC) remains challenging. A better adherence with delayed-release (DR) compared to immediate-release (IR) cysteamine at 1 year was previously shown. This study aimed to evaluate adherence to DR cysteamine at 2 years. Treatment adherence was assessed using a medication event monitoring system; adherence ranged from 0 (poor) to 2 (good). Leukocyte cystine level was measured at each 3-month visit. Long-term follow-up data (7 years after the end of the study) on self-reported adherence and quality of life was also obtained in a sub-group of patients. Seventeen patients with NC under DR cysteamine from three French centers were included at a median age of 13.9 (5.4–33.0) years. The median adherence score was 1.62 (0.03–1.98) over the 2-year follow-up, with 65

BACKGROUND:Pathogenic variants in the zinc finger protein coding genes are rare causes of intellectual disability and congenital malformations. Mutations in the ZNF148 gene causing GDACCF syndrome (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies; MIM #617260) have been reported in five individuals so far. METHODS:As a result of an international collaboration using GeneMatcher Phenome Central Repository and personal communications, here we describe the clinical and molecular genetic characteristics of 22 previously unreported individuals. RESULTS:The core clinical phenotype is characterised by developmental delay particularly in the domain of speech development, postnatal growth retardation, microcephaly and facial dysmorphism. Corpus callosum abnormalities appear less frequently than suggested by previous observations. The identified mutations concerned nonsense or frameshift variants that were mainly located in the last exon of the ZNF148 gene. Heterozygous deletion including the entire ZNF148 gene was found in only one case. Most mutations occurred de novo, but were inherited from an affected parent in two families. CONCLUSION:The GDACCF syndrome is clinically diverse, and a genotype-first approach, that is, exome sequencing is recommended for establishing a genetic diagnosis rather than a phenotype-first approach. However, the syndrome may be suspected based on some recurrent, recognisable features. Corpus callosum anomalies were not as constant as previously suggested, we therefore recommend to replace the term 'GDACCF syndrome' with 'ZNF148-related neurodevelopmental disorder'.

La diabetes insípida nefrógena congénita (DINc) es una patología hereditaria rara. Incluye formas de transmisión ligada al cromosoma X (90% de los casos) y formas de transmisión autosómica recesiva o dominante. Se caracteriza por una incapacidad renal de concentrar la orina, por resistencia del tubo colector a la acción de la vasopresina. En la forma ligada al cromosoma X, la expresión clínica suele ser muy precoz en los niños varones con existencia, desde el período neonatal o en el momento del destete, de una gran apetencia de agua, una ganancia de peso insuficiente y, en ocasiones, episodios de deshidratación hipernatrémica. En las niñas portadoras, la semiología es variable, pero también puede ser significativa. Estas formas son secundarias a mutaciones del gen que codifica el receptor V2 de la vasopresina, localizado en posición Xq28–, causantes de una pérdida de función de este receptor. Algunas de estas mutaciones pueden causar un fenotipo intermedio cuyo diagnóstico puede realizarse de forma desplazada. Las formas de transmisión autosómica recesiva o dominante se expresan también precozmente y de forma equivalente en ambos sexos. Son secundarias a mutaciones del gen que codifica el canal de agua acuaporina-2, situado en posición 12q13. El tratamiento es sintomático. Su finalidad es reducir las necesidades de agua mediante la instauración de una dieta hipoosmótica y la utilización de hidroclorotiazida y de indometacina. Este tratamiento es complicado, en particular en los lactantes. Su objetivo es mantener un estado de hidratación suficiente y prevenir los episodios de deshidratación hipernatrémica. Existen perspectivas de otros tratamientos, más específicos de algunos pacientes, por ejemplo, antagonistas no peptídicos del receptor V2 de la vasopresina que actúen como moléculas chaperonas. Como una imagen invertida de la DINc, el síndrome nefrógeno de antidiuresis inapropiada (NSIAD, nephrogenic syndrome of inappropriate antidiuresis) se relaciona con mutaciones del gen del receptor V2 y recientemente se ha relacionado también con mutaciones germinales de ganancia de función del gen GNAS que codifica la subunidad Gsα. La conformación activa permanente de estos receptores mutados provoca en los pacientes afectados un fenotipo de «secreción inapropiada de hormona antidiurética», mientras que la concentración circulante de esta hormona está disminuida.

IntroductionApproximately 8 per million children and young adults aged < 20 initiate kidney replacement therapy (KRT) per year in France. We hypothesize that social deprivation could be a determinant of childhood-onset kidney failure. The objective of this study was to estimate the incidence of pediatric KRT in France according to the level of social deprivation.MethodsAll patients < 20 years who initiated KRT from 2010 to 2015 in metropolitan France were included. Data were collected from the comprehensive French registry of KRT (REIN). We used a validated ecological index to assess social deprivation, the 2011 French version of the European Deprivation Index (EDI). We estimated the age-standardized incidence rates according to the quintiles of EDI using direct standardization and incidence rate ratio (IRR) using Poisson regression.ResultsWe included 672 children with kidney failure (58.6% males, 30.7% with glomerular or vascular disease, 43.3% starting KRT between 11 and 17 years). 38.8% were from the most deprived areas (quintile 5 of EDI). The age-standardized incidence rate increased with quintile of EDI, from 5.45 (95% CI 4.25-6.64) per million children per year in the least deprived quintile to 8.46 (95% CI 7.41-9.51) in the most deprived quintile of EDI (IRR Q5 vs Q1 1.53 95% CI 1.18-2.01).ConclusionThis study showed that even in a country with a universal healthcare system, there is a strong association between the incidence of pediatric KRT and social deprivation showing that social health inequalities appear from KRT initiation. This study highlights the need to look further into social inequalities in the earliest stage of CKD.

Background In France, kidney diseases of undetermined origin account for 5%-20% of all causes of end-stage kidney disease. We investigated the impact of social disadvantage on the lack of aetiological diagnosis of nephropathies. Methods Data from patients who started dialysis in France between 1 January 2017 and 30 June 2018 were extracted from the French Renal Epidemiology and Information Network registry. The social deprivation of each individual was estimated by the European Deprivation Index (EDI) defined by the patient's address. Logistic regression was used to perform mediation analysis to study the potential association between social deprivation and unknown nephropathy. Results Of the 7218 patients included, 1263 (17.5%) had unknown kidney disease. A total of 394 (31.4%) patients in the unknown kidney disease belonged to the most deprived quintile of the EDI [fifth quintile (Q5)], vs 1636 (27.5%) patients in the known kidney disease group. In the multivariate analysis, unknown kidney disease was associated with Q5 (odds ratio 1.40, 95% confidence interval 1.12-1.74, P = .003). Mediation analysis did not identify any variables (e.g. obesity, initiation of dialysis in emergency, number of visits to the general practitioner and nephrologist before initiation of dialysis, date of first nephrology consultation) that mediated the association between social deprivation and nephropathy of unknown origin. Conclusions Our results show that, compared with nondeprived subjects, individuals experiencing social deprivation have a higher risk of unknown nephropathy at dialysis initiation. However, mediation analysis did not identify any variables that explained the association between social deprivation and nephropathy of unknown origin.

Introduction: Hepatocyte nuclear factor 1-beta ( HNF1B ) gene variants or the chromosome 17q12 deletion (17q12del) represent the most common monogenic cause of developmental kidney disease. Although neurodevelopmental disorders have been associated with the 17q12del, specific genotype-phenotype associations with respect to kidney function evolution have not yet been fully defined. Here, we aimed to determine whether 17q12del or specific HNF1B variants were associated with kidney survival in a large patient population with HNF1B disease. Methods: This was a retrospective observational study involving 521 patients with HNF1B disease from 14 countries using the European Reference Network for rare kidney diseases with detailed information on the HNF1B genotype ( HNF1B variants or the 17q12del). Median follow-up time was 11 years with 6 visits per patient. The primary end point was progression to chronic kidney disease (CKD) stage 3 (estimated glomerular filtration rate [eGFR] <60 ml/min per 1.73 m(2)). Secondary end points were the development of hypomagnesemia or extrarenal disorders, including hyperuricemia and hyperglycemia. Results: Progression toward CKD stage 3 was significantly delayed in patients with the 17q12del compared to patients with HNF1B variants (hazard ratio [HR]: 0.29, 95% confidence interval [CI]: 0.19-0.44, P < 0.001). Progression toward CKD stage 3 was also significantly delayed when HNF1B variants involved the HNF1B Pit-1, Oct-1, and Unc-86 homeodomain (POUh) DNA-binding and transactivation domains rather than the POU-specific domain (POUs) DNA-binding domain (HR: 0.15 [95% CI: 0.06-0.37), P < 0.001 and HR: 0.25(95% CI: 0.11-0.57), P = 0.001, respectively). Finally, the 17q12del was positively associated with hypomagnesemia and negatively associated with hyperuricemia, but not with hyperglycemia. Conclusion: Patients with the 17q12del display a significantly better kidney survival than patients with other HNF1B variants; and for the latter, variants in the POUs s DNA-binding domain lead to the poorest kidney survival. These are clinically relevant HNF1B kidney genotype-phenotype correlations that inform genetic counseling.

The Lavrion mining district (SE Attica, Greece) comprises ore deposits of (1) low-grade Mo-Cu porphyry style, (2) Cu-Fe skarn, (3) high-temperature carbonate replacement Pb-Zn-Ag-(Au), and (4) vein and breccia Pb-Zn-Ag mineralizations. These are the result of the transport and deposition of economic elements from fluids that circulated from the construction to the gravitational collapse of the Hellenides-Aegean Domain along the Africa-Eurasia convergent plate boundary active for the last 80 Ma. Oceanic and continental rocks of the African plate were buried to high pressure conditions in the subduction zone. Progressive southward slab retreat was accompanied by magmatism and exhumation of metamorphic rocks along high- and low-angle detachment systems, with associated mineralized systems. The porphyry and skarn deposits are spatially and genetically related to the Plaka magmatic in tru sion dated 12 – 8 Ma. Carbonate replacement is associated with decarbonation and the liberation of CO2 during exhumation at the ductile to brittle transition. Fluorite and calcite gangue minerals enclosing the vein and breccia Pb-Zn-Ag mineralization were precipitated during brittle deformation from a fluid resulting from mixing of meteoric water with evaporated seawater closer to the surface. Base and precious metals were exploited since the Bronze Age to the late 20th century. As such, the Lavrion area represents an exceptional site to study the evolution of mining technologies through history.

ObjectiveTo evaluate the postnatal outcome of children with antenatal colonic hyperechogenicity, currently considered as a sign of lysinuria-cystinuria, but which may also be a sign of other disorders with a more severe prognosis.MethodWe carried out a French multi-centric retrospective study via 15 Multidisciplinary Center for Prenatal Diagnosis from January 2011 to January 2021. We included pregnancies for which fetal colonic hyperechogenicity had been demonstrated. We collected the investigations performed during pregnancy and at birth as well as the main clinical features of the mother and the child. We then established the prevalence of pathologies such as lysinuria-cystinuria (LC), hypotonia-cystinuria syndrome (HC), or lysinuric protein intolerance (LPI).ResultsAmong the 33 cases of colonic hyperechogenicity collected, and after exclusion of those lost to follow-up, we identified 63% of children with lysinuria-cystinuria, 8% with lysinuric rotein intolerance, and 4% with hypotonia-cystinuria syndrome.ConclusionManagement of prenatal hyperechoic colon should include a specialized consultation with a clinical geneticist to discuss further investigations, which could include invasive amniotic fluid sampling for molecular diagnosis. A better understanding of diagnoses and prognosis should improve medical counseling and guide parental decision making. What's already known about this topic ?Currently, colonic hyperechogenicity is a sign of lysinuria-cystinuria, but it can also be a sign of other disorders with a more severe prognosis.What does this study add?In this retrospective study, among fetuses with hyperechoic colon, we identified 63% of children with lysinuria-cystinuria, 8% with lysinuric protein intolerance, and 4% with hypotonia-cystinuria syndrome. These data are likely to modify the management of patients in whom a hyperechogenic fetal colon is identified.

Introduction: After six years of medication errors' (MEs) collection and analysis in a pediatric unit of a French University Hospital, the number of MEs was no longer decreasing. We then decided to set up pharmaceutical training and tools and evaluate their impact on the occurrence of ME. Materials and methods: This monocentric prospective study was carried out in the form of audits of prescriptions, preparations, and administrations before and after intervention (A1 and A2). After the analysis of A1 results, feedback was given to the teams, some tools for the proper use of medication (PUM) were distributed, and A2 was conducted. Finally, A1 and A2 results were compared. Results: Each audit included 202 observations. A total of 120 MEs were identified during A1 and 54 for A2 (p < 0.0001). The observation rate with at least 1 ME decreased from 39.11% to 21.29% (p < 0.0001), and no observation had more than two MEs during A2 in contrast to A1 (n = 12). Human factors were responsible for the majority of MEs. The audit feedback allowed professionals to feel concerned about ME. The PUM tools received an average satisfaction rating of 9/10. The staff had never participated in this type of training, and all felt it was useful to apply PUM. Conclusion: This study showed a significant impact of pharmaceutical training and tools on the pediatric PUM. Clinical pharmaceutic actions allowed us to reach our objectives and satisfied all the staff. They must, therefore, be continued to limit human factors' impact and thus contribute to the safety of drug management in pediatrics.

Major advances have been made in the management of children with chronic kidney disease (CKD) over the past 30 years. However, existing epidemiological data mainly relies on registries of chronic kidney replacement therapy. The incidence and prevalence of earlier stages of CKD remain largely unknown, but rare population-based studies suggest that the prevalence of all stages CKD may be as high as 1 % of the pediatric population. Congenital disorders including renal hypodysplasia and uropathy (CAKUT) and hereditary nephropathies account for one-half to two-thirds of childhood CKD cases in high-income countries, whereas acquired nephropathies predominate in developing countries. CKD progression is slower in children with congenital disorders than in those with glomerular nephropathy, and other risk factors for progression have also been identified. Children with CKD have poorer health-related quality of life when compared to healthy children. While survival of children with CKD has continuously improved over time, mortality remains 20 to 30 times higher than in the general pediatric population.

Au cours des trente dernières années, des progrès majeurs ont été réalisés dans la prise en charge des enfants souffrant d’une maladie rénale chronique (MRC). Cependant, les données épidémiologiques existantes proviennent essentiellement des registres de traitement de suppléance de l’insuffisance rénale terminale. L’incidence et la prévalence aux stades plus précoces de MRC restent donc mal connues, mais de rares études en population suggèrent que la prévalence de la MRC, tous stades confondus, pourrait concerner jusqu’à 1 % de la population pédiatrique. Les désordres congénitaux, incluant les hypodysplasies rénales et uropathies malformatives (CAKUT) et les néphropathies héréditaires, sont responsables de la moitié aux deux tiers des cas de MRC de l’enfant dans les pays industrialisés, alors que les néphropathies acquises prédominent dans les pays en développement. La progression de la MRC est plus lente chez les enfants avec une maladie congénitale que chez ceux ayant une néphropathie glomérulaire, et d’autres facteurs de risque de progression ont également été identifiés. Alors que la survie des enfants présentant une MRC s’est continuellement améliorée au cours du temps, la mortalité reste 20 à 30 fois supérieure à celle de la population générale pédiatrique.

Background: In spring 2019, an outbreak of Shiga toxin-producing Escherichia coli-associated hemolytic ure-mic syndrome (STEC HUS) occurred in France. Epidemiological investigations made by Sante publique France in connection with microbiological investigations at the national reference center for STEC promptly identi-fied a common exposure to consumption of raw cow's milk cheese, and confirmed a cluster affiliation of the E. coli O26:H11 outbreak strain. Here, we report the clinical characteristics of the patients, the treatment used, as well as the outcome at 1 month. Method: Patients with STEC HUS linked to the E. coli O26:H11 outbreak strain were identified from the national surveillance network of pediatric STEC HUS cases coordinated by Sante publique France. Clinical data were analyzed from the patients' hospital records obtained from the treating physicians. Results: Overall, 20 pediatric cases of STEC HUS linked to the outbreak strain were identified. Their median age of the patients was 16 months (range: 5-60). Most of them presented with diarrhea but none had received prior antibiotherapy. A total of 13 patients required dialysis; 10 patients and four patients had central nervous system (CNS) and cardiac involvement, respectively. No deaths occurred. At the 1-month follow-up, only two patients had a decreased glomerular filtration rate, below 80 mL /min/ 1.73m(2) and four had hypertension. One patient had neurological sequelae. Conclusion: The E. coli O26:H11 strain identified as the cause of an STEC HUS outbreak in France in spring 2019 is notable for the initial severe clinical presentation of the patients, with a particularly high frequency of CNS and cardiac involvement similar to the German E. coli O104:H4 outbreak described in 2011. However, despite the initial severity, the 1-month outcome was favorable in most cases. The patients' young age in this outbreak highlights the need to improve information and caregiver awareness regarding consumption of at -risk foods by young children as key preventive measures against STEC infections. (C) 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.