Lien Dossche

Hypercalciuria is Related to Osmolar Excretion in Children With Nocturnal Enuresis

PURPOSE We evaluated the incidence of hypercalciuria, defined as urinary calcium-to-creatinine ratio greater than 0.21 mg/mg, in children with nocturnal enuresis, and the association with concurrent values of diuresis and osmolar excretion. MATERIALS AND METHODS A total of 550 children admitted to a tertiary university center were included in the study. A 24-hour urine collection was performed in 8 sampling periods for measurement of calcium excretion, osmolality and diuresis. RESULTS Of the children with nocturnal enuresis 12% had 24-hour hypercalciuria. Up to 29% of the timed urine samples exhibited hypercalciuria. There was a significant correlation between calcium excretion and nocturnal diuresis volume (polyuria), low urinary osmolality, and increased sodium and osmolar excretion of nighttime urine samples (all p <0.001). CONCLUSIONS Patients referred to a tertiary enuresis center have a high incidence of hypercalciuria. However, the significant correlation between hypercalciuria and osmolar excretion and diuresis suggests that it is a comorbid factor rather than a primary pathogenic factor. As such, we cannot confirm the data from Italian studies relating nocturnal enuresis to primary hypercalciuria, and suggest instead an association with nutritional intake.

Circadian Rhythm of Glomerular Filtration and Solute Handling Related to Nocturnal Enuresis.

PURPOSE Although nocturnal polyuria in patients with monosymptomatic enuresis can largely be explained by the decreased nocturnal vasopressin secretion hypothesis, other circadian rhythms in the kidney also seem to have a role. We recently documented an absent day/night rhythm in a subgroup of desmopressin refractory cases. We explore the importance of abnormal circadian rhythm of glomerular filtration and tubular (sodium, potassium) parameters in patients with monosymptomatic enuresis. MATERIALS AND METHODS In this retrospective study of a tertiary enuresis population we collected data subsequent to a standardized screening (International Childrens Continence Society questionnaire), 14-day diary for nocturnal enuresis and diuresis, and 24-hour concentration profile. The study population consisted of 139 children with nocturnal enuresis who were 5 years or older. Children with nonmonosymptomatic nocturnal enuresis were used as controls. RESULTS There was a maintained circadian rhythm of glomerular filtration, sodium, osmotic excretion and diuresis rate in children with monosymptomatic and nonmonosymptomatic nocturnal enuresis, and there was no difference between the 2 groups. Secondary analysis revealed that in patients with nocturnal polyuria (with monosymptomatic or nonmonosymptomatic nocturnal enuresis) circadian rhythm of glomerular filtration, sodium and osmotic excretion, and diuresis rate was diminished in contrast to those without nocturnal polyuria (p <0.001). CONCLUSIONS Circadian rhythm of the kidney does not differ between patients with nonmonosymptomatic and monosymptomatic enuresis. However, the subgroup with enuresis and nocturnal polyuria has a diminished circadian rhythm of nocturnal diuresis, sodium excretion and glomerular filtration in contrast to children without nocturnal polyuria. This observation cannot be explained by the vasopressin theory alone.

Paediatric departments need to improve residents’ training in adolescent medicine and health: a position paper of the European Academy of Paediatrics

AbstractIn many European countries, paediatric junior staff has no formal training in adolescent medicine and is ill-equipped to deal with issues and health problems such as substance use, unprotected sex, eating disorders and transition to adult care. This position paper of the European Academy of Paediatrics proposes a set of competency-based training goals and objectives as well as pedagogic approaches that are expected to improve the capacity of paediatricians to meet the needs of this important segment of the paediatric population. The content has been developed from available publications and training programmes and mostly covers the generic aspects of adolescent healthcare, such as how to communicate effectively, how to review and address lifestyles, how to perform a respectful and relevant physical examination, how to address common problems of adolescents and how to support adolescents in coping with a chronic condition. Conclusion: The European Academy of Paediatrics urges national bodies, paediatric associations and paediatric teaching departments to adopt these training objectives and put them into practice, so that paediatricians will be better prepared in the future to meet the challenge of delivering appropriate and effective healthcare to adolescents.

The choice between deceased- vs living-donor renal transplantation in children: Analysis of data from a Belgian tertiary center

Pediatric renal transplantation with a living donor (LD) has superior outcome, but there is a paucity of studies analyzing the reasons for not undertaking living donation in West‐European countries. The aim of this study was to retrospectively review the choice of donor source in our center. We also aimed to identify factors which prevented transplantation with a LD. This retrospective study was performed including children aged 2‐19 years who underwent kidney transplantation (KT) at the Ghent University Hospital between 1996 and 2016. Relevant data were collected from medical files to identify the main medical, psychological, and socio‐economic factors influencing the choice of the donor source. There were 48 patients (boys n = 33) who underwent KT. Thirty‐nine patients received a deceased donor (DD) kidney and nine patients received a LD kidney. Sixteen of 48 transplantations were preemptive. The reasons for DD KT included socio‐economic factors such as single caregiver families, one or both parents with a criminal record or convictions and religious or cultural constraints (n = 15), medical considerations (n = 13), refusal of the close relatives/parents to donate (n = 7), and acceptance of an organ from a DD while prospective donor was undergoing medical screening (n = 4). The low incidence of living kidney donation can be explained by socio‐economic and medical factors. Refusal to donate is a potentially modifiable factor and strategies aimed at education and guidance of the families might contribute to a higher incidence of living donation in our setting.

Ethical considerations of researchers conducting pediatric clinical drug trials: a qualitative survey in two Belgian university children’s hospitals

There is a general consensus about the underlying theoretical ethical principles that ground the practice of pediatric clinical trials: scientific necessity, good risk/benefit ratio, minimized burden, and parental consent/child assent. However, these principles are so broadly construed that it is not always clear how they should be applied in clinical practice. We conducted a qualitative study at Ghent University Hospital and the hospital of the Dutch-speaking university of Brussels on how researchers weigh ethical principles, assess the risk/benefit balance, estimate patient experience, and experience informed consent procedures in pediatric drug studies. Based on our assessment of the burden and risk versus benefit ratio in 62 pediatric drug research protocols, we selected 21 studies for further study to maximize diversity. Twenty-seven researchers (17 physicians, 10 study nurses) completed a qualitative survey about their study. We compared their responses to our assessments. The risk benefit assessment of our participants about their own research projects resembled our assessment almost perfectly. Assessing burden appeared to be more subjective. The researchers were confident in their ability to obtain valid consent. However, we question whether this confidence is warranted.Conclusion: We argue for constant ethical reflexivity in pediatric clinical trials, because broad ethical principles are not always easy to apply to specific situations.What is Known:• Several international guidelines and a large body of scientific literature indicate a broad consensus about the basic ethical framework for pediatric clinical trials, based on risk benefit assessment and respect for autonomy.• Little is known about how researchers implement these broad principles in practice.What is New:• Researchers’ risk/benefit assessments about their own studies resembled the assessment of neutral peers, assessing burden was more subjective.• Researchers were very confident in their ability to obtain valid informed consent.

Influence of fluid intake on functional bladder volume and nighttime diuresis in nocturnal enuresis

Abstracts 48th ESPN Meeting, Brussels, September 2015s 48th ESPN Meeting, Brussels, September 2015 O 01 CAN EARLY RECOGNITION OFAKI IN CHILDREN BE ACHIEVED BY USING AN ALGORITHM (PRELIMINARY RESULTS): ON BEHALF OF BRITISH ASSOCIATION FOR PAEDIATRIC NEPHROLOGY Jelena Stojanovic, Nabil Melhem, Sheetal Bhojani, Manish D Sinha, David Milford Evelina London Childrens Hospital, London, UK; Royal Hospital for Sick Children, Glasgow, Scotland; Birmingham Childrens Hospital, Birmingham, UK Introduction: The aim of the study was to validate recently proposed algorithm ‘Standardising early identification of Acute Kidney Injury’ introduced byNHSEngland in a paediatric setting and to investigate recognition and management of AKI. This multi-centre national project was supported by UK Renal Registry and British Association for Paediatric Nephrology. Material and methods: In part one of the audit, all creatinine measurements performed at each of six centres over a six month period were evaluated electronically using the algorithm. In part two, 180 children from six centres were randomly selected and their case notes reviewed. Here, we report preliminary results on data analysed from two tertiary children’s and one district general hospital in the UK. Information was obtained from paper and electronic patient’s notes. AKI stage 1 is a rise of >1.5x baseline creatinine level; AKI stage 2 is a rise of>2x baseline and AKI stage 3 is a rise of>3x baseline. Results: 33,663 creatinine measurements were analysed during the study period using the AKI algorithm.We identified 1,940 AKI 1 episodes (604 children), 479 AKI 2 (158 children) and 756 AKI 3 (112 children). Overall 666 unique children had one or more AKI episodes.We reviewed case notes of 66 children (39 boys) age range 28 days to 17 years. On clinical review of case notes, AKI was recognised in 18 patients (27.3%) only. Of all patients, 17% had prexisting renal condition. 94% children had a follow up arranged with creatinine normalising in 75% of those tested. A third of patients had urine tested and two thirds had medication dosage adjusted to estimated GFR. Conclusions: The proposed algorithm provides an electronic means of identifying children with AKI and highlighting its severity. Our preliminary data suggest that AKI remains clinically under recognised in clinical settings. Timely recognition and optimal management of AKI is important to improve longer term renal outcomes. O 02 EPIGENETIC REGULATION BY HDAC PROTEINS PLAYSACRITICALROLE INTHEPROGRESSIONOFRENAL FIBROSIS Scott Manson, Qiusha Guo, Katelynn Moore, Paul Austin Washington University, Washington, The United States of America Introduction: Chronic kidney disease is associated with changes in the expression of approximately 10% of the genome. The histone deacetylases (HDACs) are a family of 10 related proteins which are among the most widely expressed and crucial regulators of gene transcription. In this study, we examine the biologic and therapeutic importance of HDAC proteins during disease progression. Material and methods: Chronic renal injury was modeled in vivo in mice by unilateral ureteral obstruction (UUO). The role of HDAC proteins was assessed by using a variety of molecular techniques and treatment with the broad spectrumHDAC inhibitor Trichostatin A (TSA). Results:UUO leads to a dramatic increase in the protein levels of 9 of the 10 HDAC isoforms. Notably, there is a 6.1-fold increase in HDAC8 expression that localizes specifically to pericyte-derived myofibroblasts, the cell population which accounts for the majority of matrix production during renal fibrosis. To better understand the importance of these findings, we treated mice with the HDAC inhibitor TSA. This resulted in a 3.4-fold increase in the anti-fibrotic gene BMP7, a 41.6% decrease in the matrix protein COLIA1, and a 61.6% decrease in the myofibroblast differentiation marker α-SMA following UUO. These changes in gene expression culminate in a 77.9% decrease in the interstitial proliferative response, a 43.0% decrease in myofibroblast number, 31.1% decrease in renal fibrosis, 42.8% decrease in apoptosis, and a 43.4% decrease in the loss of renal architecture. [All results are p<0.05] Conclusions: Chronic renal injury is associated with a dramatic increase in HDAC protein levels that stimulates pro-fibrotic gene expression and suppresses anti-fibrotic gene expression. Importantly, treatment with HDAC inhibitors reverses these changes in gene expression and inhibits the development of renal fibrosis. This suggests that HDAC inhibitors may serve as effective therapies to inhibit disease progression. O 03 ECULIZUMAB TREATMENT IN SEVERE PEDIATRIC STEC-HUS, A MULTICENTRIC RETROSPECTIVE STUDY Percheron Lucas, Gramada Raluca, Decramer Stephane, Harambat Jerome, Eckart Philippe, Bourdat-michel Guylhene, Leroy Valerie, Sellier-leclerc Anne-laure, Adra Anne-laure, Allain-launay Emma, Berard Etienne, Bouchireb Karim, Fila Marc, Pietrement Christine, Merieau Elodie, Lapeyraque Anne-laure, Chehade Hassid, Fremeaux-bacchi Veronique, Dimeglio Chloe, Garnier Arnaud Service De Nephrologie Medecine Interne, Hopital Des Enfants, Chu Purpan, Toulouse, France; Service De Neuroradiologie Diagnostique Et Thérapeutique, Chu Purpan, Toulouse, France; Service De Nephrologie Pediatrique, Hopital Pellegrin-enfants, Chu Bordeaux, Bordeaux, France; Service De Pediatrie Medicale, Hopital Cote De Nacre, Chu Caen, Caen, France; Service De Pediatrie, Hopital Couple-enfants, Chu Grenoble, Grenoble, France; Service De Nephrologie Pediatrique, Hopital Jeanne De Flandre, Chu Lille, Lille, France; Service De Nephrologie Pediatrique, Hopital Femme Mere Enfant, Hospices Civils De Lyon, Lyon, France; Service De Nephrologie Pediatrique, Hopital Arnaud De Villeneuve, Chu Montpellier, Montpellier, France; Service De Nephrologie Pediatrique, Hopital Mere-enfants, Chu Nantes, Nantes, France; Service De Nephrologie Pediatrique, Hopital Archet 2, Chu Nice, Nice, France; Service De Nephrologie Pediatrique, Hopital Necker Enfants Malades, Assistance Publique-hopitaux De Paris, Paris, France; Service De Nephrologie Pediatrique, Hopital Robert Debre-paris, Assistance Publique-hopitaux De Paris, Paris, France; Service De Pediatrie, Hopital Americain, Chu Reims, Reims, France; Service De Nephrologie, Hopital Clocheville, Chu Tours, Tours, France; Service De Nephrologie Pediatrique, Chu De Sainte-justine, Montreal, Canada; Service De Nephrologie Pediatrique, Chu De Lausanne, Lausanne, Switzerland; Laboratoire D’immunologie, Hopital Europeen Georges Pompidou, Assistance Publique-hopitaux De Paris, DOI 10.1007/s00467-015-3158-7 Pediatr Nephrol (2015) 30:1543–1730• OnabotulinumtoxinA is a safe and effective treatment for therapy resistant OAB in non-neuropathic children. • It can be a useful treatment option for therapy resistant incontinence and/or enuresis. • With one single treatment, over 50% cure rate may be achieved in a therapy resistant patient population. • The aim of this study is to analyze results and side effects after OnabotulinumtoxinA detrusor injection treatment in children in order to define its place in the treatment of non-neuropathic OAB • Effect on both incontinence and enuresis is reported. • Therapy resistant enuresis is to our knowledge not previously reported as indication for the use of OnabotulinumtoxinA RESULTS OF ONABOTULINUMTOXIN-A IN CHILDREN WITH THERAPY RESISTANT OVERACTIVE BLADDER: 10-YEAR EXPERIENCE

Mogelijke valkuilen bij de interpretatie van de waterstofademtest bij kinderen

Children who present with chronic diarrhea, flatulence and/or abdominal pain possibly suffer from malabsorption of carbohydrates. Most frequently this depends on a lactase deficiency causing a carbohydrate overload in the colon. The fermentation of these carbohydrates by anaerobic bacteria can provoke osmotic diarrhea and gas production in the bowel. The hydrogen-breath test can easily be used to diagnose which kind of carbohydrates are causing the symptoms. When carbohydrates are digested by anaerobic bacteria, hydrogen is set free, which can be measured in exhaled breath. The results are plotted on a curve. Certain circumstances influence this test. False negative results are seen in 5 to 10% non-producers due to the absence of hydrogen producing bacteria in their colon flora or in case of recent antibiotic use. False positive results can be caused by the presence of undigestable oligosaccharides or carbohydrates in the colon or also in case of small intestinal bacterial overgrowth. It is necessary to evaluate test results in relation to symptoms during and shortly after the test procedure. These symptoms need to resemble the complaints which raised the suspicion on the carbohydrate malabsorption.