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Our objective was to establish the rate of neurological involvement in Shiga toxin-producing Escherichia coli–hemolytic uremic syndrome (STEC-HUS) and describe the clinical presentation, management and outcome. A retrospective chart review of children aged ≤ 16 years with STEC-HUS in Children’s Health Ireland from 2005 to 2018 was conducted. Laboratory confirmation of STEC infection was required for inclusion. Neurological involvement was defined as encephalopathy, focal neurological deficit, and/or seizure activity. Data on clinical presentation, management, and outcome were collected. We identified 240 children with HUS; 202 had confirmed STEC infection. Neurological involvement occurred in 22 (11%). The most common presentation was seizures (73%). In the neurological group, 19 (86%) were treated with plasma exchange and/or eculizumab. Of the 21 surviving children with neurological involvement, 19 (91%) achieved a complete neurological recovery. A higher proportion of children in the neurological group had renal sequelae (27% vs. 12%, P = .031). One patient died from multi-organ failure.Conclusion: We have identified the rate of neurological involvement in a large cohort of children with STEC-HUS as 11%. Neurological involvement in STEC-HUS is associated with good long-term outcome (complete neurological recovery in 91%) and a low case-fatality rate (4.5%) in our cohort. What is Known:• HUS is associated with neurological involvement in up to 30% of cases.• Neurological involvement has been reported as predictor of poor outcome, with associated increased morbidity and mortality. What is New:• The incidence of neurological involvement in STEC-HUS is 11%.• Neurological involvement is associated with predominantly good long-term outcome (90%) and a reduced case-fatality rate (4.5%) compared to older reports.

Since 1972, eighteen patients (10 females/8 males) have been detected by newborn bloodspot screening (NBS) with neonatal-onset Maple Syrup Urine Disease (MSUD) in Ireland. Patients were stratified into three clusters according to clinical outcome at the time of data collection, including developmental, clinical and IQ data. A fourth cluster comprised of two early childhood deaths; a third patient died as an adult. We present neuroimaging and EEG together with clinical and biochemical data. Incidence of MSUD (1972-2018) was 1 in 147,975. Overall good clinical outcomes were achieved with 15/18 patients alive and with essentially normal functioning (with only the lowest performing cluster lying beyond a single standard deviation on their full scale intelligence quotient, FSIQ). Molecular genetic analysis revealed genotypes hitherto not reported, including a possible digenic inheritance state for the BCKDHA and DBT genes in one family. Treatment has been based on early implementation of emergency treatment, diet, close monitoring and even dialysis in the setting of acute metabolic decompensation. A plasma leucine ≥400 μmol/L (outside therapeutic range) was more frequently observed in infancy or during adolescence, possibly due to infections, hormonal changes or noncompliance. Children require careful management during metabolic decompensations in early childhood as this represented a key risk period in our cohort. A high level of metabolic control can be achieved through diet with early implementation of a 'sick day' regime and, in some cases, dialysis as a rescue therapy. The Irish cohort, despite largely classical phenotypes, achieved good outcomes in the NBS era, underlining the importance of early diagnosis and skilled multidisciplinary team (MDT) management. This article is protected by copyright. All rights reserved.

Background CAKUT are the most common cause of end-stage renal failure in children (Pediatr Nephrol. 24, 2009, 1719). Many children with CAKUT have poor urinary drainage which can compromise post-transplant outcome. Identifying safe ways to manage anatomical abnormalities and provide effective urinary drainage is key to transplant success. Much debate exists regarding optimum urinary diversion techniques. The definitive formation of a continent urinary diversion is always preferable but may not always be possible. We explore the role of ureterostomy formation at transplantation in a complex pediatric group. Methods We report six pediatric patients who had ureterostomy formation at the time of transplantation at the National Paediatric Transplant Centre in Dublin, Ireland. We compared renal function and burden of urinary tract infection to a group with alternative urinary diversion procedures and a group with normal bladders over a 5-year period. Results There was no demonstrable difference in estimated glomerular filtration rate between the groups at 5-year follow-up. The overall burden of UTI was low and similar in frequency between the three groups. Conclusions Ureterostomy formation is a safe and effective option for temporary urinary diversion in children with complex abdominal anatomy facilitating transplantation; it is, however, important to consider the implications and risk of ureterostomy for definitive surgery after transplantation.

Background Following cryptogenic stroke, guidelines recommend cardiac monitoring for occult atrial fibrillation (AF). We aimed to evaluate predictors of AF during long‐term implantable cardiac monitoring. Methods and Results We studied 293 consecutive patients who underwent implantable cardiac monitor implant (Medtronic LINQ) following hospitalization for cryptogenic stroke at the University of Rochester Medical Center from January 2013 to September 2018. Multivariable Cox proportional hazards regression modeling was used to identify predictors of AF during long‐term monitoring. At 36 months of follow‐up, the cumulative rate of implantable cardiac monitor–detected AF events was 32% in the total study population. Multivariable analysis identified age ≥70 years as the most powerful predictor of the development of AF events during follow‐up (hazard ratio, 2.28 [95% CI, 1.39–3.76]; P =0.001). Replacing age with the CHA 2 DS 2 ‐VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, age, sex category) score resulted in a weaker association, for which each 1‐point increment in the CHA 2 DS 2 ‐VASC score was associated with an 18% increased risk of developing AF (95% CI, 1.00–1.38; P =0.047). Consistent results were shown using Kaplan–Meier analysis by age and by the CHA 2 DS 2 VASc score. Conclusions Cryptogenic stroke patients continue to develop AF episodes during 36 months of implantable cardiac monitoring following the index event. Age is the most powerful predictor of occult AF in this population.

Background Vascular access is required for haemodialysis (HD), a form of renal replacement therapy required when a child has acute or end stage kidney disease (ESKD). Central venous catheter (CVC) line infections are the second most common cause of vascular access loss in the long term HD patient, commonly caused by poor hand hygiene practices, clinical environment or inadequate sterilisation procedures. In the literature the reported rates of infection range from 0.8–4.8 episodes/1000 catheter days in this patient group. Aim To audit CVC line related infection rates in our tertiary HD unit in Temple Street Children’s University Hospital (TSCUH) over a 5 year period. Methods A retrospective review was carried out on all patients who had HD from January 2012- January 2017 (inclusive) using a CVC. Results/Findings 34 patients required HD, of which 44% were female and 56% male. Twenty-three patients (68%) were aged between 5–10 years of age. Dysplastic kidneys was the most common reason for requiring HD (n=9, 26.2%). Eight patients required HD for 1–6 months, 5 patients for 6–12 months, 19 patients for 12–48 months, and 2 patients for >60 months. Five out of 34 children developed CVC line infections with an overall infection rate of 0.22 episodes per 1000 catheter days. Loss of protective caps was the main reason for infection (n=3). Staph-aureous, pseudomonas oryzihabitans, enterococcus faecalis and mixed coagulase negative staphylococci were the identified organisms causing infection. Conclusions CVC line infections in long-term HD patients attending TSCUH are maintained at a low rate in comparison to published data. Strict application of Aseptic Non Touch Technique shows favourable results without the need for prophylactic antibiotics locks. Future work includes a cost benefit analysis of this practice.

Despite improvements in cardiovascular implantable electronic device (CIED) design and functionality, the risk of device infection is on the rise. Complete removal of the device is recommended following CIED infection. However, the optimal management of large lead vegetations (> 2 cm) remains

Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system, leading to complement overactivation. A humanized anti-C5 monoclonal antibody, eculizumab, has been available for the treatment of aHUS since 2011. The long-term safety and efficacy of this novel drug in the pediatric population remain under review. We present a child with a hybrid CFH/CFHR3 gene who, having had multiple disease relapses despite optimal treatment with plasma exchange, commenced eculizumab therapy in August 2010. She remains relapse free in follow-up at 52 months, and treatment has been well tolerated. The risk of meningococcal disease during this treatment is recognized. Despite vaccination against meningococcal disease and appropriate antibiotic prophylaxis, our patient developed meningococcal bacteremia 30 months into treatment. She presented with nonspecific symptoms but recovered without sequelae with appropriate treatment. We recommend that children be vaccinated against invasive meningococcal infection before beginning eculizumab therapy and take appropriate antibiotic prophylaxis during treatment, and we suggest that vaccine responses should be checked and followed annually. Clinicians need to maintain a high index of suspicion for invasive meningococcal disease. Neither vaccination nor antibiotic prophylaxis provides complete protection in patients on eculizumab therapy. The appropriate dosage of eculizumab needed to achieve remission in aHUS in the pediatric population is unknown. Having achieved remission in our patient, we monitor eculizumab and CH50 levels to evaluate ongoing blockade of the terminal complement cascade. Such information may help guide dosing intervals in the future.

Background: Epstein-Barr virus (EBV) was the first human virus identified to express microRNA (miRNA). To date, 44mature miRNAs are encoded for within the EBV genome. EBV miRNAs have not been profiled in paediatric renal transplant recipients. In this study, we investigated circulating EBV miRNA profiles as novel biomarkers in paediatric renal transplant patients. Methods: Forty-two microRNAs encoded within 2 EBV open reading frames (BART and BHRF) were examined in renal transplant recipients who resolved EBV infection (REI) or maintained chronic high viral loads (CHL), and in non-transplant patients with acute infectious mononucleosis (IM). Results: Plasma EBV-miR-BART2-5p was present in higher numbers of IM (7/8) and CHL (7/10) compared to REI (7/12)patients. A trend was observed between the numbers of plasma EBV miRNAs expressed and EBV viral load (p < 0.07).Several EBV-miRs including BART7-3p, 15, 9-3p, 11-3p, 1-3p and 3-3p were detected in IM and CHL patients only. Thelytic EBV-miRs, BHRF1-2-3p and 1-1, indicating active viral replication, were detected in IM patients only. One CHL patient developed post-transplant lymphoproliferative disease (PTLD) after several years and analysis of 10 samples over a 30-month period showed an average 24-fold higher change in plasma EBV-miR-BART2-5p compared to the CHL group and 110-fold higher change compared to the REI group.Conclusions Our results suggest that EBV-miR-BART2-5p, which targets the stress-induced immune ligand MICB to escape recognition and elimination by NK cells, may have a role in sustaining high EBV viral loads in CHL paediatric kidney transplant recipients.

Immature animals demonstrate an amplified heat shock response following a variety of insults compared with that seen in mature animals (M). The potential role of the heat shock response in modulating immature tolerance to injury was compared between rat pups, 10 postnatal days of age ( P10), and M. Baseline levels of the heat shock transcription factor (HSF-1) were substantially elevated in P10 compared with M animals. In uninjured P10 pups, HSF-1 level was comparable to that of M animals subjected to 45 min of ischemia. As anticipated, the integrity of suspensions of tubules exposed to anoxia was preserved in P10 animals (23% LDH release) compared with M (40%), P < 0.01. The effect of targeted inhibition of HSF-1 on tubular integrity was studied using a cyclic oligonucleotide decoy. The HSF-1 decoy increased the severity of anoxic injury in P10 pups to a level comparable with M animals. LDH release was 33% in decoy-treated P10 tubules compared with 40% in M. When P10 tubules were treated with scrambled decoy, resistance to anoxia remained intact (24%). The increased vulnerability of the tubular suspension to injury was specific to the HSF-1 decoy and proportional to the dose of decoy applied. This study demonstrates maturation in the abundance of HSF-1 in the immature rat kidney. The loss of resistance of immature tubules to anoxia with specific inhibition of HSF-1 may be due to its effect on the heat shock response or other signaling pathways of critical pathobiological importance in renal cell injury.

Hemodialysis (HD) in infants is usually used when peritoneal dialysis (PD) has failed. We describe our experience with HD, outlining the morbidity, complications, and outcomes for infants weighing less than 10 kg managed with HD for more than 6 months over a 10-year period.A retrospective review of the clinical notes was conducted to collect demographic information, anthropometric data, dietary history, site and form of vascular access, details of HD prescription, complications, and outcomes.Nine patients weighing less than 10 kg were hemodialyzed for more than 6 months. Median age at commencement was 9 months. Median weight and height standard deviation score (SDS) at commencement of HD were -2.14 and -0.61, respectively, and at the end they were -1.56 and -1.61. Median energy intake was 96.6 kcal/kg/day and protein intake was 1.66 g/kg/day. Median number of line revisions was 0.32 line changes/patient year. Median central venous catheter (CVC) longevity was 13 months. Mean rate of line infection was 0.14/patient year. Median time on HD was 27 months. Median age at transplantation was 3.4 years.This case series shows that chronic HD is a viable management option in children10 kg. Access issues can be minimized with good line care to maximize line longevity and minimize line infection rates.

Children on hemodialysis are at increased risk of thrombosis, especially when dialyzed via a central venous catheter (CVC); there are limited published data regarding the safety and efficacy of tinzaparin in this group. We conducted a retrospective chart review of all children in the National Pediatric Hemodialysis Centre for Ireland diagnosed with a CVC thrombus and treated with subcutaneous tinzaparin over a 10 year period. Seven children were treated with subcutaneous tinzaparin for 10 CVC thrombi. Tinzaparin was commenced at 175 IU/kg/day and the dose was titrated by measuring anti-factor Xa levels, aiming for levels of 0.3-1.0 IU/ml. Treatment was continued until resolution of the CVC thrombus. Restoration of normal flows during dialysis occurred within 3 days in all patients. There were no episodes of bleeding and all children tolerated the treatment well.

Renal ischemia is the result of a complex series of events, including decreases in oxygen supply (hypoxia) and the availability of cellular energy (ATP depletion). In this study, the functional activation of two stress-responsive transcription factors, i.e. , heat shock factor-1 (HSF-1) and hypoxia-inducible factor-1 (HIF-1), in the kidney was assessed. When rats were subjected to 45 min of renal ischemia, electrophoretic mobility shift assays of kidney nuclear extracts revealed rapid activation of both HIF-1 and HSF. Western blot analyses further demonstrated that this activation resulted in increased expression of the HSF and HIF-1 target genes heat shock protein-72 and heme oxygenase-1, respectively. Whether hypoxia or ATP depletion alone could produce similar activation patterns in vitro was then investigated. Renal epithelial LLC-PK 1 cells were subjected to either ATP depletion (0.1 μM antimycin A and glucose deprivation) or hypoxia (1% O 2 ). After ATP depletion, HSF was rapidly activated (within 30 min), whereas HIF-1 was unaffected. In contrast, hypoxia led to the activation of HIF-1 but not HSF. Hypoxic activation of HIF-1 was observed within 30 min and persisted for 4 h, whereas no HSF activation was detected even with prolonged periods of hypoxia. HIF-1 was transcriptionally active in LLC-PK 1 cells, as demonstrated by luciferase reporter gene assays using the vascular endothelial growth factor promoter or a synthetic promoter construct containing three hypoxia-inducible elements. Interestingly, intracellular ATP levels were not affected by hypoxia but were significantly reduced by ATP depletion. These findings suggest that HIF-1 is activated specifically by decreased O 2 concentrations and not by reduced ATP levels alone. In contrast, HSF is activated primarily by metabolic stresses associated with ATP depletion and not by isolated O 2 deprivation. In vivo , the two transcription factors are simultaneously activated during renal ischemia, which might account for observed differences between in vivo and in vitro epithelial cell injury and repair. Selective modulation of either pathway might therefore be of potential interest for modification of the response of the kidney to ischemia, as well as the processes involved in recovery from ischemia.

A previously well 12-year-old boy presented with a 1month history of polydipsia, polyuria, and lethargy. Over that period, he had been drinking at least 3 l of water daily, reported feeling thirsty, and needed to pass urine approximately every 30 min. His parents also reported that he had weight loss over the previous month with reduced appetite secondary to nausea. Of note, he had a long-standing history of drinking approximately 1 l of cow’s milk daily. He had no recent acute illnesses or fevers and reported no pain, discomfort, or respiratory distress. He had been treated with azathioprine for 3 years in the past for intractable eczema. His blood glucose level checked by his general practitioner was normal. Physical examination revealed significant bilateral inguinal lymphadenopathy and a 2-cm palpable liver edge. There were patches of dry skin attributed to previously diagnosed eczema. His cardiovascular, respiratory, neurological, ENT, and musculoskeletal examinations were otherwise unremarkable. There was an evident BCG scar. Vital signs were within normal limits. Laboratory investigations revealed acute renal impairment, hypercalcemia, and a mild transaminitis: urea 15.2 mmol/l, creatinine 149 mmol/l, serum calcium 3.38 mmol/l, ionized calcium 1.78 mmol/l, serum phosphate 1.42 mmol/l, sodium 139 mmol/l, potassium 3.7 mmol/l, AST 76 U/l, ALT 114 U/l, and lactate dehydrogenase 416 U/l. Serum intact parathyroid hormone levels were suppressed at