Jo Dehoorne

Desmopressin Resistant Nocturnal Polyuria Secondary to Increased Nocturnal Osmotic Excretion

PURPOSE We investigated the role of increased solute excretion in children with desmopressin resistant nocturnal enuresis and nocturnal polyuria. MATERIALS AND METHODS A total of 42 children with monosymptomatic nocturnal enuresis and significant nocturnal polyuria with high nocturnal urinary osmolality (more than 850 mmol/l) were not responding to desmopressin. A 24-hour urinary concentration profile was obtained with measurement of urine volume, osmolality, osmotic excretion and creatinine. The control group consisted of 100 children without enuresis. RESULTS Based on osmotic excretion patients were classified into 3 groups. Group 1 had 24-hour increased osmotic excretion, most likely secondary to a high renal osmotic load. This was probably diet related since 11 of these 12 patients were obese. Group 2 had increased osmotic excretion in the evening and night, probably due to a high renal osmotic load caused by the diet characteristics of the evening meal. Group 3 had deficient osmotic excretion during the day, secondary to extremely low fluid intake to compensate for small bladder capacity. CONCLUSIONS Nocturnal polyuria with high urinary osmolality in our patients with desmopressin resistant monosymptomatic nocturnal enuresis is related to abnormal increased osmotic excretion. This may be explained by their fluid and diet habits, eg daytime fluid restriction, and high protein and salt intake.

Familial Mediterranean fever mutations lift the obligatory requirement for microtubules in Pyrin inflammasome activation

Significance Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by more than 310 mutations in the gene MEFV, which encodes Pyrin. Pyrin recently was shown to trigger inflammasome activation in response to Rho GTPase-modifying bacterial toxins. Here we report that Clostridium difficile infection and intoxication with its enterotoxin TcdA engage the Pyrin inflammasome. Moreover, activation of the Pyrin inflammasome, but not other inflammasomes, was hampered by microtubule-depolymerizing drugs in mouse and humans. Unexpectedly, we found that FMF mutations render Pyrin activation independent of microtubules. Thus, our findings provide a conceptual framework for understanding Pyrin signaling and enable functional diagnosis of FMF. Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease worldwide. It is caused by mutations in the inflammasome adaptor Pyrin, but how FMF mutations alter signaling in FMF patients is unknown. Herein, we establish Clostridium difficile and its enterotoxin A (TcdA) as Pyrin-activating agents and show that wild-type and FMF Pyrin are differentially controlled by microtubules. Diverse microtubule assembly inhibitors prevented Pyrin-mediated caspase-1 activation and secretion of IL-1β and IL-18 from mouse macrophages and human peripheral blood mononuclear cells (PBMCs). Remarkably, Pyrin inflammasome activation persisted upon microtubule disassembly in PBMCs of FMF patients but not in cells of patients afflicted with other autoinflammatory diseases. We further demonstrate that microtubules control Pyrin activation downstream of Pyrin dephosphorylation and that FMF mutations enable microtubule-independent assembly of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) micrometer-sized perinuclear structures (specks). The discovery that Pyrin mutations remove the obligatory requirement for microtubules in inflammasome activation provides a conceptual framework for understanding FMF and enables immunological screening of FMF mutations.

Desmopressin Toxicity Due to Prolonged Half-Life in 18 Patients With Nocturnal Enuresis

PURPOSE Desmopressin has been used extensively for primary nocturnal enuresis and it is associated with a low incidence of adverse effects. The only reported serious side effect is seizure or altered levels of consciousness resulting from water intoxication, which has been reported for the nasal spray. We describe 18 children with clinical symptoms of water intoxication due to the prolonged bioactivity of desmopressin nasal spray. MATERIALS AND METHODS We evaluated 18 patients with clinical suspicion of prolonged desmopressin bioactivity during treatment with intranasal desmopressin for primary nocturnal enuresis. The control group consisted of 50 children with primary nocturnal enuresis and proven nocturnal polyuria who were treated with the same desmopressin regimen. RESULTS All patients had prolonged maximal urinary concentration capacity and delayed restoration of daytime diluting capacity (p <0.01). Of the patients 15 had the characteristic clinical symptoms of water intoxication with vomiting, headache, decreased consciousness and hyponatremia. We suspect that these symptoms are secondary to prolonged desmopressin bioactivity. CONCLUSIONS Prolonged desmopressin bioactivity may increase the risk of water intoxication.

Diagnostic value of MRI features of sacroiliitis in juvenile spondyloarthritis.

AIM To determine the diagnostic utility of magnetic resonance imaging (MRI) features of sacroiliitis in juvenile spondyloarthritis (JSpA). MATERIALS AND METHODS This was a prospective study of 80 paediatric patients who underwent MRI of the sacroiliac joints that were clinically suspected to have sacroiliitis. The prevalence of MRI features of active and structural lesions of sacroiliitis was recorded. Patients were classified according to the International League of Association for Rheumatology criteria. The MRI findings were compared to the final clinical diagnosis. RESULTS Sacroiliitis was seen in 25/80 (31%) patients. MRI showed active inflammation in 23 patients (29%): synovial enhancement (28%), high short tau inversion recovery (STIR)-signal in the joint space (29%), bone marrow oedema (BMO; 20%), and capsulitis (8%). Structural changes were present in 14 patients (18%): erosion (14%), fat infiltration (13%), sclerosis (8%), and ankylosis (1%). Of all MRI features, ankylosis (100%), capsulitis (98%), BMO (96%), and erosion (96%) had the highest specificity for JSpA; global diagnostic impression (55%) and synovial enhancement (52%) were the MRI features with the highest sensitivity. The likelihood ratios (LR+) for diagnosis of JSpA were high for BMO (10.5), capsulitis (7.5), global diagnostic impression (6.9), and erosions (6.75), but greater for BMO concomitant with synovial enhancement (LR+ 19.5) and for erosion concomitant with BMO (LR+ 12) or synovial enhancement (LR+ 13.5). CONCLUSION There are multiple features of active inflammation and structural damage visible at MRI of the sacroiliac joints that can provide a specific diagnosis of JSpA when present in children with suspected sacroiliitis. Synovial enhancement is the MRI feature with the highest sensitivity for JSpA. If BMO is seen concomitant with synovial enhancement or erosion, the diagnosis of JSpA is very likely. Ankylosis, capsulitis, bone marrow oedema, and erosion all have a high specificity for JSpA. Absence of MRI findings of sacroiliitis does not exclude the diagnosis of JSpA.

Therapeutic plasma exchange in children with acute autoimmune central nervous system disorders.

Background There is a growing evidence for autoimmunity in acute central nervous system (CNS) disorders and treatment with therapeutic plasma exchange (TPE) may be considered. The aim was to share our experience on the clinical application of TPE in these disorders and to present a reproducible protocol which can be used even in small children. Methods We present a series of 8 children aged 2-12 years with transverse myelitis, Bickerstaffs brainstem encephalitis, neuromyelitis optica, and acute paraneoplastic or unspecified encephalitis in whom TPE was used as a second-line or rescue treatment. Results A total of 104 TPE sessions were performed where 80–110 ml/kg of plasma was exchanged using 4% albumin solution and fresh frozen plasma. Six episodes of TPE-related adverse events were documented. Fibrinogen concentrations decreased after the first TPE, whereas platelets decreased gradually. One patient died in the course of the acute illness. Three children achieved a complete resolution of symptoms, 2 children have mild sequelae; whereas 2 children remain paraplegic after a follow-up of 3 to 17 months. Conclusions We report 8 children with presumably autoimmune-mediated, acute CNS disorders treated with TPE as a rescue therapy. Although the effect of TPE can only be inferred, 5 children had a good clinical outcome. TPE is feasible even in small children with acute autoimmune CNS disorders.

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.

Tacrolimus predose concentration is associated with hypertension in pediatric liver transplant recipients

Background: The aim of the study was to analyze the incidence of hypertension in pediatric liver transplantation (LT) recipients using ambulatory blood pressure measurements (ABPM) and to identify factors associated with hypertension. We also investigated whether hypertension or tacrolimus predose concentration (TAC C0) was associated with increased left ventricular (LV) wall thickness. Patients and Methods: On a retrospective longitudinal base, we included 39 pediatric LT recipients. Median time since transplantation was 65 months (range: 11–183). Two consecutive ABPM were analyzed with a median time interval of 13 months. Data from echocardiographic evaluation parallel to the baseline ABPM were analyzed. All patients except 1 were prescribed tacrolimus. The median TAC C0 was 4 ng/mL (range 0.9–11.2). Univariate and multivariate logistic regression models were fitted to identify factors associated with systolic and diastolic hypertension and LV wall thickness. Results: Twenty-two of 39 children were hypertensive at baseline and 19 of 32 were hypertensive at follow-up. At baseline 10 (26%) children had masked systolic hypertension. TAC C0 was associated with systolic (P = 0.007, Exp(B) 2.02, 95% CI 1.2–3.3) and diastolic (P = 0.044, Exp(B) 1.48, 95% CI 1.0–2.2) hypertension. LV wall thickness was increased in children after LT compared with healthy population, but it was not associated with hypertension or TAC C0. Conclusions: Given the high prevalence of masked hypertension, ABPM should be performed in all pediatric LT recipients. Systolic and diastolic hypertension is associated with TAC C0; therefore, children with a higher target TAC C0 require a more intensive blood pressure surveillance.

Factors regulating 1,25-dihydroxyvitamin D3 concentrations in liver transplant recipients

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

Eight years experience with in-center nocturnal hemodialysis

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

Intensive therapeutic plasma exchange in children with acute autoimmune neurological disorders

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