Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease.

Although a rare disease, bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage kidney disease in children. Ultrasound-based prenatal prediction of postnatal kidney survival in CAKUT pregnancies is far from accurate. To improve prediction, we conducted a prospective multicenter peptidome analysis of amniotic fluid spanning 140 evaluable fetuses with CAKUT. We identified a signature of 98 endogenous amniotic fluid peptides, mainly composed of fragments from extracellular matrix proteins and from the actin binding protein thymosin-ß4. The peptide signature predicted postnatal kidney outcome with an area under the curve of 0.96 in the holdout validation set of patients with CAKUT with definite endpoint data. Additionally, this peptide signature was validated in a geographically independent sub-cohort of 12 patients (area under the curve 1.00) and displayed high specificity in non-CAKUT pregnancies (82 and 94% in 22 healthy fetuses and in 47 fetuses with congenital cytomegalovirus infection respectively). Change in amniotic fluid thymosin-ß4 abundance was confirmed with ELISA. Knockout of thymosin-ß4 in zebrafish altered proximal and distal tubule pronephros growth suggesting a possible role of thymosin ß4 in fetal kidney development. Thus, recognition of the 98-peptide signature in amniotic fluid during diagnostic workup of prenatally detected fetuses with CAKUT can provide a long-sought evidence base for accurate management of the CAKUT disorder that is currently unavailable.

Effect of conservative treatment on the renal outcome of children with primary hyperoxaluria type 1.

Primary hyperoxaluria type 1 results from alanine:glyoxylate aminotransferase deficiency. Due to genotype/phenotype heterogeneity in this autosomal recessive disorder, the renal outcome is difficult to predict in these patients and the long-term impact of conservative management in children is unknown. We report here a multicenter retrospective study on the renal outcome in 27 affected children whose biological diagnosis was based on either decreased enzyme activity or identification of mutations in the patient or his siblings. The median age at first symptoms was 2.4 years while that at initiation of conservative treatment was 4.1 years; 6 children were diagnosed upon family screening. The median follow-up was 8.7 years. At diagnosis, 15 patients had an estimated glomerular filtration rate (eGFR) below 90, and 7 children already had stage 2-3 chronic kidney disease. The median baseline eGFR was 74, which rose to 114 with management in the 22 patients who did not require renal replacement therapy. Overall, 20 patients had a stable eGFR, however, 7 exhibited a decline in eGFR of over 20 during the study period. In a Cox regression model, the only variable significantly associated with deterioration of renal function was therapeutic delay with a relative risk of 1.7 per year. Our study strongly suggests that early and aggressive conservative management may preserve renal function of compliant children with this disorder, thereby avoiding dialysis and postponing transplantation.

Should We Assess Pituitary Function in Children After a Mild Traumatic Brain Injury? A Prospective Study.

Objective: The aim of this study was to evaluate the frequency of hypopituitarism following TBI in a cohort of children who had been hospitalized for mild TBI and to identify the predictive factors for this deficiency. Design: A prospective study was conducted on children between 2 and 16 years of age who had been hospitalized for mild TBI according to the Glasgow Coma Scale between September 2009 and June 2013. Clinical parameters, basal pituitary hormone assessment at 0, 6, and 12 months, as well as a dynamic testing (insulin tolerance test) 12 months after TBI were performed. Results: The study included 109 children, the median age was 8.5 years. Patients were examined 6 months (n = 99) and 12 months (n = 96) after TBI. Somatotropic deficiency (defined by a GH peak <20 mUI/l in two tests, an IGF-1 <-1SDS and a delta height <0SDS) were confirmed in 2 cases. One case of gonadotrophic deficiency occurred 1 year after TBI among 13 pubertal children. No cases of precocious puberty, 5 cases of low prolactin level, no cases of corticotropic insufficiency (cortisol peak <500 nmol/l) and no cases diabetes insipidus were recorded. Conclusion: Pituitary insufficiency was present 1year after mild TBI in about 7% of children. Based on our results, we suggest testing children after mild TBI in case of clinical abnormalities. i.e., for GH axis, IGF-1, which should be assessed in children with a delta height <0 SDS, 6 to 12 months after TBI, and a dynamic GH testing (preferentially by an ITT) should be performed in case of IGF-1 <-1SDS, with a GH threshold at 20 mUI/L. However, if a systematic pituitary assessment is not required for mild TBI, physicians should monitor children 1 year after mild TBI with particular attention to growth and weight gain.

Effect of hydrochlorothiazide on urinary calcium excretion in dent disease: an uncontrolled trial.

BACKGROUND: Thiazide doses equivalent to 1 to 2 mg/kg/d of hydrochlorothiazide (HCTZ) have been proposed to correct hypercalciuria and prevent kidney failure in patients with Dent disease. However, they can cause adverse metabolic effects in the long term. In treating hypertension in children, lower thiazide doses have been shown to be as effective and well tolerated. STUDY DESIGN: Uncontrolled trial, with forced-titration sequential open-label study design. SETTING & PARTICIPANTS: 7 boys with genetically confirmed Dent disease and mild phenotype (neither overt sodium wasting nor kidney failure). INTERVENTION: After a 1-month run-in period, patients sequentially received amiloride (5 mg/d) alone (1 month) and then for 3 periods of 2 months in association with increasing doses of HCTZ (<0.2, 0.2 to 0.4, and 0.4 to 0.8 mg/kg/d). OUTCOMES: Urinary calcium excretion and extracellular volume indicators. MEASUREMENTS: At the end of each period, 2 daily 24-hour urinary collections were performed on the days preceding admission. Blood and spot urine samples also were collected. RESULTS: A greater HCTZ dose increased renin, aldosterone, and plasma protein concentrations. Amiloride alone had no effect on calcium excretion. The greatest HCTZ doses decreased spot urinary calcium excretion by 42% compared with baseline (median, 0.3; minimum, maximum, 0.2, 0.8 versus median, 0.8; minimum, maximum, 0.4, 1.1, respectively; P = 0.03). However, patients developed adverse reactions, including muscle cramps (n = 2), biological (n = 7) or symptomatic hypovolemia (n = 1), hypokalemia (n = 4), and hyponatremia (n = 1), which all corrected after treatment withdrawal. LIMITATION: Small sample size and absence of a control group. CONCLUSION: HCTZ doses greater than 0.4 mg/kg/d decreased calcium excretion, but were associated with significant adverse events. Thiazide diuretic therapy should be considered with caution in children with Dent disease.

A qualitative study on the educational needs of young people with chronic conditions transitioning from pediatric to adult care.

OBJECTIVES: Although patient education is recommended to facilitate the transition from pediatric to adult care, a consensus has not been reached for a particular model. The specific skills needed for the transition to help in facilitating the life plans and health of young people are still poorly understood. This study explored the educational needs of young people with diverse chronic conditions during their transition from pediatric to adult care. METHODS: Qualitative semi-structured interviews were conducted with 17 young people with chronic conditions. A thematic analysis was conducted to examine the data. RESULTS: Five themes emerged from the data, identified through the following core topics: learning how to have a new role, learning how to adopt a new lifestyle, learning how to use a new health care service, maintaining a dual relationship with pediatric and adult care, and having experience sharing with peers. CONCLUSION: A shift in perspective takes place when the transition is examined through the words of young people themselves. To them, moving from pediatric to adult care is not viewed as the heart of the process. It is instead a change among other changes. In order to encourage a transition in which the needs of young people are met, educational measures could focus on the acquisition of broad skills, while also being person-centered.

Isolated hypospadias: The impact of prenatal exposure to pesticides, as determined by meconium analysis.

Although endocrine-disrupting chemicals (EDCs, including pesticides) are thought to increase the risk of hypospadias, no compounds have been formally identified in this context. Human studies may now be possible via the assessment of meconium as a marker of chronic prenatal exposure. The objective of the present study was to determine whether or not prenatal exposure to pesticides (as detected in meconium) constitutes a risk factor for isolated hypospadias. In a case-control study performed between 2011 and 2014 in northern France, male newborns with isolated hypospadias (n = 25) were matched at birth with controls (n = 58). Newborns with obvious genetic or hormonal anomalies, undescended testis, micropenis, a congenital syndrome or a family history of hypospadias were not included. Neonatal and parental data were collected. Foetal exposure was assessed by determining the meconium concentrations of the pesticides or metabolites (organophosphates, carbamates, phenylurea, and phenoxyherbicides) most commonly used in the region. Risk factors were assessed in a multivariate analysis. The pesticides most commonly detected in meconium were organophosphates (in up to 98.6% of samples, depending on the substance) and phenylurea (>85.5%). A multivariate analysis revealed an association between isolated hypospadias and the presence in meconium of the phenylurea herbicide isoproturon and of the phenoxyherbicide 2-methyl-4-chlorophenoxyacetic acid (odds ratio [95% confidence interval]: 5.94 [1.03-34.11] and 4.75 [1.20-18.76]) respectively). We conclude that prenatal exposure to these two herbicides (as assessed by meconium analysis) was correlated with the occurrence of isolated hypospadias. The results of our case-control study (i) suggest that prenatal exposure to pesticides interferes with the development of the male genitalia, and (ii) emphasize the importance of preventing pregnant women from being exposed to EDCs in general and pesticides in particular.

Response to Elwood, M. et al., Comment on: Maternal Exposure to Domestic Hair Cosmetics and Occupational Endocrine Disruptors Is Associated with a Higher Risk of Hypospadias in the Offspring. Int. J. Environ. Res. Public Health 2017, 14, 27.

Dear Editor, Thank you for inviting us to reply to a "Comment" paper to our published paper "Maternal Exposure to Domestic Hair Cosmetics and Occupational Endocrine Disruptors Is Associated with a Higher Risk of Hypospadias in the Offspring" (Authors: Elodie Haraux, Karine Braun, Philippe Buisson, Erwan Stéphan-Blanchard, Jannick Ricard, Camille Devauchelle, Bernard Boudailliez, Pierre Tourneux, Richard Gouron, Karen Chardon).[...].

Erratum: Haraux, E., et al. Maternal Exposure to Domestic Hair Cosmetics and Occupational Endocrine Disruptors Is Associated with a Higher Risk of Hypospadias in the Offspring. Int. J. Environ. Res. Public Health 2016, 14, 27.

Due to an error during production, some data presented in Table 1 in the Experimental section of the published paper [1] were incorrect.[...].

Maternal Exposure to Domestic Hair Cosmetics and Occupational Endocrine Disruptors Is Associated with a Higher Risk of Hypospadias in the Offspring.

Pregnant women are exposed to various chemical products at home and at work. Some of these products contain endocrine-disrupting chemicals (EDCs) such as cosmetics, pesticides, industrial chemicals, heavy metals, plastics or medications that could alter sexual differentiation and increase the risk of hypospadias. We evaluated maternal occupational and household exposures that could constitute risk factors for hypospadias. From 2011 to 2014, we enrolled 57 full-term newborns with hypospadias and three randomly selected controls per case (162 control newborns), matched for gestational age, from 11 maternity units in Picardy, France. Neonatal and parental data were collected at birth (personal characteristics, maternal lifestyle, and medical history). Maternal occupational exposure was assessed by a job-exposure matrix for EDCs from a job history questionnaire completed by mothers. Odds ratios (OR) and 95% confidence intervals (CI) were calculated with univariate and multivariable logistic regression, and adjusted for relevant covariates. Multivariate analysis showed a strong association between hypospadias and potential maternal occupational exposure to EDCs and maternal household use of hair cosmetics (OR 6.1, 95% CI: 1.1-34.9; OR: 9.6, 95% CI: 1.4-66.1, respectively). Our results suggest that maternal occupational exposure to EDCs is a risk factor for hypospadias and suggests a possible influence of household use of hair cosmetics during early pregnancy on the incidence of hypospadias in the offspring. A larger study with more accurate exposure assessment should evaluate the impact of EDCs in hair cosmetics on the incidence of hypospadias.

[Renal late effects in patients treated for cancer in childhood]. / Complications rénales à long terme chez les patients traités pour un cancer dans l'enfance.

Impaired renal function may occur following multimodal treatment of cancer in childhood. Renal late effects caused by chemotherapy, renal surgery and/or radiotherapy are now well described; but little is known about their prevalence and time of development. Herein, we provide a synthesis of the different renal complications that may occur with their physiopathology in relation with specific treatment exposures. This review summarized the literature that supported the recommendations issued by the long-term follow-up group of the "Société française des cancers de l'enfant (SFCE)" for childhood cancer survivors at risk for nephrotoxicity (www.sfce.org ; www.soc-nephrologie.org/SNP/index.htm). We developed these monitoring elements and the lifestyle recommendations for all asymptomatic survivors.

Coping strategies associated with suicidal behaviour in adolescent inpatients with borderline personality disorder.

OBJECTIVES: To compare the coping strategies of adolescents with borderline personality disorder (BPD) to the coping strategies of adolescents without BPD, and to explore the association of coping with suicidal ideation and attempts among adolescents with BPD. METHOD: Adolescent inpatients (n = 167) aged 13 to 17 years were admitted after suicide attempts and evaluated within 10 days, using the abbreviated version of the Diagnostic Interview for Borderlines-Revised, the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version supported by a team consensus best estimate method for the primary diagnosis, the Adolescent Coping Scale, and the Columbia-Suicide Severity Rating Scale. RESULTS: Firstly, compared with adolescents without BPD, adolescents with BPD relied more on nonproductive coping strategies, mostly avoidant strategies, and less on productive coping strategies. Secondly, coping appeared as a factor associated with suicidal ideation in adolescents with BPD. While while controlling for age, sex, and depression, multivariate analyses showed a significant positive association between the coping strategy to focusing on solving the problem and suicidal ideation. CONCLUSION: The use of avoidant strategies by adolescents with BPD could be viewed as attempts to increase emotional regulation. Problem-solving strategies in the immediate aftermath of a suicide attempt may prevent adolescents with BPD from overcoming a crisis and may increase suicidal ideation.

Darbepoetin, effective treatment of anaemia in paediatric patients with chronic renal failure.

Darbepoetin alpha (DA) is a unique long-acting treatment for anaemia in patients with chronic renal failure (CRF). This study assessed the mean dose of DA to achieve and maintain haemoglobin (Hb) levels between 11 g/dl and 13 g/dl in CRF children aged 11 years to 18 years. This observational, prospective study was conducted in 39 patients treated with DA. Twenty-nine patients were switched from recombinant human erythropoietin (r-HuEPO), and ten patients were naive to r-HuEPO. Naive patients received initial doses of 0.45 microg/kg of DA. Switched patients received a dose adjusted to the prior dose of r-HuEPO (200 IU r-HuEPO:1 microg DA). Among the switched patients, 79.3% received dialysis. No naive patients underwent dialysis. Overall, 74% of patients showed increased Hb level, with a mean value of 11.6 +/- 1.6 g/dl, using a mean DA dose of 0.63 +/- 0.48 microg/kg per week, and 66.7% patients reached the target Hb level. Hb increased in naive patients from 9.5 (95% CI: 7.7, 11.4) to 11.7 (95% CI: 10.9, 12.6) g/dl and in switched patients from 11.1 (95% CI: 10.6, 11.5) to 11.5 (95% CI: 10.8, 12.2) g/dl). Higher doses of DA were needed in the "switched" than in the "naive" patients to maintain Hb levels over 11 g/dl, respectively 0.73 (95% CI: 0.54, 0.92) and 0.34 (95% CI: 0.16, 0.52) microg/kg per week. Our results indicate the doses of DA necessary to treat CRF patients aged 11 years to 18 years. DA was an effective treatment to stabilise CRF patients at extended dosing intervals.

Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome.

Mutations in factor H (CFH), factor I (IF), and membrane cofactor protein (MCP) genes have been described as risk factors for atypical hemolytic uremic syndrome (aHUS). This study analyzed the impact of complement mutations on the outcome of 46 children with aHUS. A total of 52% of patients had mutations in one or two of known susceptibility factors (22, 13, and 15% of patients with CFH, IF, or MCP mutations, respectively; 2% with CFH+IF mutations). Age <3 mo at onset seems to be characteristic of CFH and IF mutation-associated aHUS. The most severe prognosis was in the CFH mutation group, 60% of whom reached ESRD or died within <1 yr. Only 30% of CFH mutations were localized in SCR20. MCP mutation-associated HUS has a relapsing course, but none of the children reached ESRD at 1 yr. Half of patients with IF mutation had a rapid evolution to ESRD, and half recovered. Plasmatherapy seemed to have a beneficial effect in one third of patients from all groups except for the MCP mutation group. Only eight (33%) of 24 kidney transplantations that were performed in 15 patients were successful. Graft failures were due to early graft thrombosis (50%) or HUS recurrence. In conclusion, outcome of HUS in patients with CFH mutation is catastrophic, and posttransplantation outcome is poor in all groups except for the MCP mutation group. New therapies are urgently needed, and further research should elucidate the unexplained HUS group.