Vaccination practices in pediatric transplantation: A survey among member centers of the European reference network TransplantChild.

BACKGROUND: There is considerable variation in vaccination practices between pediatric transplant centers. This study aims to evaluate active immunization attitudes and practices among ERN-TransplantChild centers and identify potential areas of improvement that could be addressed by shared evidence-based protocols. METHODS: A cross-sectional questionnaire of attitudes and practices toward immunization of pediatric SOT and HSCT candidates and recipients was sent to a representative member of multidisciplinary teams from 27 European centers belonging to the ERN-TransplantChild. RESULTS: A total of 28/62 SOT programs and 6/12 HSCT programs across 21 European centers participated. A quarter of centers did not have an on-site protocol for the immunizations. At the time of transplantation, pediatric candidates were fully immunized (80%-100%) in 57% and 33% of the SOT and HSCT programs. Variations in the time between vaccine administration and admission to the waiting list were reported between the centers, with 2 weeks for inactivated vaccines and variable time (2-4 weeks) for live-attenuated vaccines (LAVs). Almost all sites recommended immunization in the post-transplant period, with a time window of 4-8 months for the inactivated vaccines and 16-24 months for MMR and Varicella vaccines. Only five sites administer LAVs after transplantation, with seroconversion evaluated in 80% of cases. CONCLUSIONS: The immunization coverage of European pediatric transplant recipients is still inconsistent and far from adequate. This survey is a starting point for developing shared evidence-based immunization protocols for safe vaccination among pediatric transplant centers and generating new research studies.

Successful low-dose immunotherapy after kidney transplantation in a 10-year-old girl with Schimke immuno-osseous dysplasia.

BACKGROUND: This case report highlights a successful steroid-free, low-dose immunosuppressive protocol for renal transplantation in a pediatric patient with Schimke immuno-osseous dysplasia with excellent 7-year patient and graft survival. Schimke immuno-osseous dysplasia is a rare multisystem disorder involving the kidney. Renal transplantation is a therapeutic option, but posttransplant mortality is high due to severe infections and posttransplant lymphoproliferative disease. METHODS: A 10-year-old girl diagnosed with Schimke immuno-osseous dysplasia and end-stage renal disease underwent an AB0-compatible living-related kidney transplantation, with no donor-specific antibodies. Our standard immunosuppression protocol was modified due to the risk of infection. Basiliximab was used as induction therapy, and a reduced dose of mycophenolate mofetil and tacrolimus was initiated following transplantation, maintaining the patient on a low tacrolimus target (3-5 µg/L). Mycophenolate mofetil was discontinued after 8 weeks due to neutropenia and the patient was kept on tacrolimus as monotherapy. Five years posttransplant the patient developed acute onset of neurological symptoms, consisting of ataxia, lack of voluntary coordination, balance, aphasia and dysphagia, and diplopia. She recovered without neurological deficits within 6 weeks. Extensive evaluation revealed no pathology. To avoid a possible a component of tacrolimus-induced cerebral vasoconstriction, the immunosuppressive therapy was changed to everolimus. RESULTS: Seven years posttransplant, the patient has experienced no serious infections, no rejections, and had excellent graft function, and no de novo donor-specific antibodies. CONCLUSIONS: The present results indicate that low-dose immunosuppressive therapy after renal transplantation with low immunological risk should be considered for patients with Schimke immuno-osseous dysplasia.

Children with acute pyelonephritis need medical re-evaluation when home-treated with oral antibiotics.

AIM: To investigate the efficacy and safety of home-treatment with oral piv-mecillinam or amoxicillin-clavulanate in children with acute pyelonephritis. METHODS: Children aged over 6 months diagnosed with culture confirmed pyelonephritis at Danish Paediatric Departments were home-treated with piv-mecillinam (tablets) or amoxicillin-clavulanate (liquid or tablets). Follow-up was performed by phone (second treatment day) and clinical review of the patients in the hospital (day three). RESULTS: Four hundred eighteen children were included. In total, 333/418 (80%) responded well to the initial oral antibiotic treatment. 85/418 (20%) were changed to another treatment of these 47/418 (11%) to a second-line oral antibiotic and 38/418 (9%) to intravenous antibiotics due to insufficient clinical improvement or bacterial resistance. Bacterial resistance was similar for piv-mecillinam and amoxicillin-clavulanate: 4/74 (5%) versus 33/333 (10%) (p = 0.22). Insufficient clinical improvement, despite no resistance, primarily occurred in children treated with piv-mecillinam: 16/74 (22%) versus 28/344 (8%) (p < 0.001), and predominantly occurred in piv-mecillinam treated children <5 years: 7/20 (35%) versus 9/54 (17%) (p < 0.05), potentially because of problems with piv-mecillinam tablets. In the study population no cases of death or septicemia developed after start of initial oral treatment. CONCLUSION: A home-treatment regime for pyelonephritis in children >6 months is safe; however, during treatment, clinical re-evaluation is required as in 20% of cases a change in treatment was necessary.

Characteristics of Danish children registered with and pharmacologically treated for hypertension.

INTRODUCTION: A previous study found that 0.04% of Danish children were registered with hypertension, among whom 54% were treated pharmacologically. Our study describes pharmacologically treated cases at the onset of antihypertensive therapy, noting whether the evaluation of target-organ damage could be improved. METHODS: Our review of the medical records of children under 16 years living in Central and Eastern Denmark from April 2014 to May 2015 found that 119 children were registered with an International Classification of Diseases, tenth edition diagnosis of hypertension and treated with antihypertensive medicine. RESULTS: The cohort consisted of 61% boys and 39% girls (p = 0.01). The majority of patients (80%) had secondary hypertension. Renal aetiology was found in 52%. Echocardiography, retinal examination and examination for proteinuria were undertaken in 77%, 74% and 100%, respectively. Both echocardiography and retinal examination were undertaken in 61% of patients with renal aetiology. Among the remaining patients, 95% and 89% underwent these examinations, respectively (p less than 0.001 and p less than 0.001). Abnormal echocardiography, abnormal retinal examination and proteinuria were found in 39%, 16% and 66%, respectively, of patients with renal aetiology and in 30%, 24% and 35% of the remaining patients (p = 0.3, p = 0.4 and p less than 0.001). CONCLUSIONS: Examination for target-organ damage was performed less often in patients with hypertension of renal aetiology than in the remaining patients. Examination for target-organ damage is recommended in all hypertensive children to determine whether treatment is indicated to reduce long-term morbidity. FUNDING: The study received funding from the Novo Nordisk Foundation, grant number NNF15OC0015702 and from Amager-Hvidovre Hospital Foundation. TRIAL REGISTRATION: not relevant.

Screen-based media use and blood pressure in preschool-aged children: A prospective study in the Odense Child Cohort.

Aims: To examine prospective and cross-sectional associations between screen time and blood pressure (BP) in preschool children. Methods: The Odense Child Cohort study started in January 2010. Children who were born in the municipality of Odense underwent a clinical examination at 3 and 5 years of age and their parents were asked to complete a questionnaire. A total of 628 children were included in the prospective analysis and 964 children were included in two cross-sectional analyses at 5 years of age. Multivariable adjusted linear and logistic regression models were computed to examine prospective and cross-sectional associations between screen time and BP with adjustment for putative confounding factors. Results: No significant prospective association was found between a 2-year change in screen time and systolic BP (0.55 BP percentile change per 1 h increase in screen time, 95% confidence interval (CI) -1.51 to 2.60) and diastolic BP (0.74 BP percentile change per 1 h increase in screen time, 95% CI -1.09 to 2.57). No significant cross-sectional association was observed between screen time (⩽1 h/day, >1-2 h/day, >2 h/day) and the prevalence of high BP at 5 years of age. Exposure to screen time before bedtime 2-5 days/week and ⩾6 days/week was significantly associated with a greater prevalence of high BP compared with screen time before bedtime 0-1 day/week (odds ratios 1.57 (95% CI 1.02-2.42) and 1.82 (95% CI 1.18-2.89), respectively. Conclusions: No prospective association was found between screen time and BP. However, a significant cross-sectional association was found between screen time before bedtime and high BP in preschool children.

Pediatric Inflammatory Bowel Diseases: Should We Be Looking for Kidney Abnormalities?

Background: Kidney disease has been reported in adults with inflammatory bowel disease (IBD) and is regarded an extraintestinal manifestation or more rarely a side effect of the medical treatment. Methods: In this cross-sectional study we describe the extent of kidney pathology in a cohort of 56 children with IBD. Blood and urine samples were analyzed for markers of kidney disease and ultrasonography was performed to evaluate pole-to-pole kidney length. Results: We found that 25% of the patients had either previously reported kidney disease or ultrasonographic signs of chronic kidney disease. The median kidney size compared with normal children was significantly reduced. In a multivariate linear mixed model, small kidneys significantly correlated with the use of infliximab, whereas the use of enteral nutritional therapy was associated with larger kidneys. Conclusion: Children with IBD are at risk of chronic kidney disease, and the risk seems to be increased with the severity of the disease.

Hearing impairment and renal failure associated with RMND1 mutations.

Recently, two research groups reported that mutations in RMND1 were associated with encephalopathy, elevated lactate, hypotonia, and in some patients seizures or myoclonia in individuals from two consanguineous families. A combined respiratory chain deficiency and a defect in mitochondrial protein translation was found. In this study, we report two siblings who are compound heterozygous for the mutations, c.713A>G and c.1003delG, in RMND1. Respiratory chain enzymatic analysis and BN-PAGE showed a combined OXPHOS deficiency. Western blot analysis indicated normal levels of RMND1, but the assembly of the RMND1 homopolymeric complex was highly impaired. The two siblings had a markedly milder phenotype and longer survival compared to previously reported patients. In addition, they had renal failure and hearing impairment. These two newly described patients contribute to delineation of the clinical spectrum associated with RMND1 aberrations.

Long-term experience of steroid-free pediatric renal transplantation: effects on graft function, body mass index, and longitudinal growth.

Increased focus on the potential negative side effects of steroid usage in pediatric transplantation has led to steroid minimization or steroid-free transplantation. In this study, we report results after complete steroid avoidance in renal transplantation in the period 1994-2009. We evaluate the effects of complete steroid avoidance on allograft function, BMI, and linear growth. The majority of transplanted children were induced with antithymocyte globulin and immunosuppressed with a calcineurin inhibitor and mycophenolate mofetil. Steroids were given only when rejection occurred or due to comorbidities. Anthropometric data were collected from 65 transplantations in 60 children. Patient survival was 93%; graft survival was 81% after five yr (N = 42) and 63% after 10 yr (N = 16). Acute rejection within the first year of transplantation was 9%. The distribution of the children's BMI before transplantation was normal; the mean BMI-SDS was 0.21 before transplantation, and this value remained stable during the next five yr. Post-transplantation the children demonstrated significant improved growth as the mean height-SDS increased significantly from -1.7 to -1.1. Catch-up growth was most pronounced in the youngest (< six yr). Steroid-free immunosuppression in pediatric renal transplantation is safe and protects against steroid-induced obesity and short stature.

Longitudinal changes in blood pressure during weight loss and regain of weight in obese boys and girls.

OBJECTIVE: To investigate blood pressure (BP) in relation to changes in body mass index (BMI) in obese children during weight loss and subsequent weight regain. DESIGN: A longitudinal study of obese boys and girls investigated through a 12-week weight loss intervention with follow-up investigations spanning 28 months. Results shown are from baseline; day 14, 33, and 82 during weight loss; and at months 10, 16 and 28 during follow-up. PATIENTS: One hundred and fifteen obese children, 53 boys and 62 girls (8-15 years) with a median BMI standard deviation score (SDS) at baseline of 2.78 in boys, and 2.70 in girls. Ninety children completed the weight loss programme and 68 children entered the follow-up programme. METHODS: Height, weight, systolic blood pressure (SBP), and diastolic BP (DBP) were recorded and analysed using a general linear mixed model. RESULTS: Fifty-one percent of the obese children were pre or hypertensive at baseline. Both DBP and SBP declined significantly with weight loss, but a divergent response was found in the timing of the rebound in hypertension during the weight regain phase, that is DBP increased during weight regain, whereas SBP remained lower than baseline during 28 months of continuous weight regain. CONCLUSION: The effect of weight reduction upon obesity-associated hypertension is noticeable and suggests the importance of an intensified childhood obesity treatment strategy in order to reduce the burden of future cardiovascular disease.