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Allograft outcome; Hyperparathyroidism; Kidney transplantation Resultado del aloinjerto; Hiperparatiroidismo; Trasplante de riñón Resultat de l'aloempelt; Hiperparatiroïdisme; Trasplantament de ronyó Introduction Little is known about the consequences of deranged chronic kidney disease–mineral and bone disorder (CKD-MBD) parameters on kidney allograft function in children. We examined a relationship between these parameters over time and allograft outcome. Methods This registry study from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) collected data at baseline, months 1, 3, 6, 9, and 12 after transplant; and every 6 months thereafter up to 5 years. Survival analysis for a composite end point of graft loss or estimated glomerular filtration rate (eGFR) ≤30 ml/min per 1.73 m2 or a ≥50% decline from eGFR at month 1 posttransplant was performed. Associations of parathyroid hormone (PTH), calcium, phosphate, and 25-hydroxyvitamin D (25(OH)D) with allograft outcome were investigated using conventional stratified Cox proportional hazards models and further verified with marginal structural models with time-varying covariates. Results We report on 1210 patients (61% boys) from 16 European countries. The composite end point was reached in 250 grafts (21%), of which 11 (4%) were allograft losses. In the conventional Cox proportional hazards models adjusted for potential confounders, only hyperparathyroidism (hazard ratio [HR], 2.94; 95% confidence interval [CI], 1.82–4.74) and hyperphosphatemia (HR, 1.94; 95% CI, 1.28–2.92) were associated with the composite end point. Marginal structural models showed similar results for hyperparathyroidism (HR, 2.74; 95% CI, 1.71–4.38), whereas hyperphosphatemia was no longer significant (HR, 1.35; 95% CI, 0.87–2.09), suggesting that its association with graft dysfunction can be ascribed to a decline in eGFR. Conclusion Hyperparathyroidism is a potential independent risk factor for allograft dysfunction in children. This study was supported by a research grant from the European Society for Paediatric Nephrology to AP. The authors gratefully acknowledge the funding of the Cooperative European Paediatric Renal Transplant Initiative Registry by a grant from the Dietmar Hopp Stiftung, the European Society for Paediatric Nephrology, and the German Society for Paediatric Nephrology and by grants from the pharmaceutical companies Astellas and Novartis.

BackgroundAdolescence is a time of significant change for patients, guardians and clinicians. The paediatrician must ensure patients develop the necessary skills and knowledge required to transition and to function as an independent entity, with autonomy over their own care. The transfer from paediatric to adult care carries an increased risk of graft-related complications attributable to a multitude of reasons, particularly non-adherence to immunosuppressive medicines and poor attendance at scheduled appointments. This systematic review was conducted to ascertain the transitional care models available to clinicians caring for kidney transplant recipients and to compare the approach in each respective case.MethodsA systematic review was performed, in a methodology outlined by the PRISMA guidelines. OVID MEDLINE and EMBASE databases were searched for studies that outlined valid, replicable models pertaining to transitional care of paediatric kidney transplant recipients between 1946 and Quarter 3 of 2021. The reference lists of selected articles were also perused for further eligible studies and experts in the field were consulted for further eligible articles. Two investigators assessed all studies for eligibility and independently performed data extraction. Any discrepancies were settled by consensus.ResultsA total of 1121 abstracts were identified, which was reduced to 1029 upon removal of duplicates. A total of 51 articles were deemed appropriate for full-text review and critical appraisal. A total of 12 articles that described models for transition pertaining to kidney transplant patients were included in qualitative synthesis. Every paper utilized a different transition model. All but one model included a physician and nurse at minimum in the transition process. The involvement of adult nephrologists, medical social work, psychology and psychiatry was variable. The mean age for the initiation of transition was 13.4 years (range: 10–17.5 years). The mean age at transfer to adult services was 18.3 years (range: 16–20.5 years).ConclusionsDespite the well-established need for good transitional care for paediatric solid-organ transplant recipients, models tailored specifically for kidney transplant recipients are lacking. Further research and validation studies are required to ascertain the best method of providing effective transitional care to these patients. Transitional care should become a standardized process for adolescents and young adults with kidney transplants.

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.

Background: Preexistent LUTD are considered a hostile environment, which might negatively impact KTx survival. In such cases, surgical reconstruction of the bladder is required. However, there is still disagreement on the optimal timing of the reconstruction procedure. Methods: This is a multicenter analysis of data from the CERTAIN Registry. Included were 62 children aged 8.18 ± 4.90 years, with LUTD. Study endpoints were the duration of initial posttransplant hospitalization, febrile UTIs, and a composite failure endpoint comprising decline of eGFR, graft loss, or death up to 5 years posttransplant. Outcome was compared to matched controls without bladder dysfunction. Results: Forty-one patients (66.1%) underwent pretransplant and 14 patients (22.6%) posttransplant reconstruction. Bladder augmentation was performed more frequently in the pretransplant (61%) than in the posttransplant group (21%, p =.013). Outcome in the pre- and posttransplant groups and in the subgroups of patients on pretransplant PD with major bladder surgery either pre- (n = 14) or posttransplant (n = 7) was comparable. Outcomes of the main study cohort and the matched control cohort (n = 119) were comparable during the first 4 years posttransplant; at year 5, there were more events of transplant dysfunction in the study cohort with LUTD than in controls (p =.03). Conclusions: This multicenter analysis of the current practice of LUTD reconstruction in pediatric KTx recipients shows that pre- or posttransplant surgical reconstruction of the lower urinary tract is associated with a comparable 5-year outcome. in press

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.

Item does not contain fulltext Infantile nephropathic cystinosis (INC) is an inheritable lysosomal storage disorder characterized by lysosomal cystine accumulation, progressive kidney disease, and multiple extrarenal complications (ERCs). Cysteamine postpones the onset of end-stage kidney disease (ESKD) and reduces the incidence of ERCs; however, cysteamine is generally initiated upon establishment of the renal Fanconi syndrome (FS) and partial loss of kidney function, whereas data on long-term effects of cysteamine administered from neonatal age are lacking. An international multicenter retrospective cohort study of siblings with INC was set up to investigate the outcome in relation to age at initiation of cysteamine versus CTNS genotype, with attention to patients treated with cysteamine from neonatal age. None of the siblings treated from neonatal age (n = 9; age 10 ± 6 years) had reached ESKD, while 22% of their index counterparts (n = 9; age 14 ± 5 years) had commenced renal replacement therapy. Siblings treated with cysteamine from the onset of symptoms at a younger age compared with their index counterparts, reached ESKD at a significant older age (13 ± 3 vs. 10 ± 3 years, p = 0.002). In contrast, no significant difference in ERCs was observed between sibling and index patients, independently from the age at initiation of cysteamine. The CTNS genotype had no impact on the overall outcome in this cohort. In INC, presymptomatic treatment with cysteamine results in a better renal outcome in comparison to treatment initiated from the onset of symptoms. This justifies including cystinosis into newborn screening programs. SYNOPSIS: In infantile nephropathic cystinosis, presymptomatic treatment with cysteamine improves the renal outcome which justifies the inclusion of cystinosis into newborn screening programs. 01 januari 2023

Rare diseases are any disease affecting fewer than five people in 10,000. More than 8000 rare diseases and 50-75% of all rare diseases affect children. The purpose of this review was to critically appraise and synthesize existing literature relating to the impact of rare diseases on children's day-to-day lives.An integrative literature review was conducted using the CINAHL Plus, PsycINFO, and PubMed databases. Studies were included if they were a primary source was published between the years 2005 and 2019 and written in the English language.Eight primary sources met the inclusion criteria.Seven main themes emerged from the review as follows: (i) the experience of stigmatisations, (ii) self-consciousness, (iii) restrictions in independent living, (iv) developing resilience/coping strategies, (v) psychological and emotional impact, (vi) social impact vs social connectedness and (vii) transition challenges.The experience of having a rare illness differed across different age groups. Children (typically aged 3-10) with rare diseases generally view themselves and their lives the same way like their healthy peers. They were more likely to report being adaptive and resilient than those aged 12 or older. Young people reported being different compared to young children, and they faced numerous challenges related to their illness.To provide the best possible level of care for children and families with rare disorders, health services must be informed and equipped to provide the necessary supports specific to the unique needs of children and young people living with rare diseases.

Cystinosis is an autosomal recessive storage disease due to impaired transport of cystine out of lysosomes. Since the accumulation of intracellular cystine affects all organs and tissues, the management of cystinosis requires a specialized multidisciplinary team consisting of pediatricians, nephrologists, nutritionists, ophthalmologists, endocrinologists, neurologists' geneticists, and orthopedic surgeons. Treatment with cysteamine can delay or prevent most clinical manifestations of cystinosis, except the renal Fanconi syndrome. Virtually all individuals with classical, nephropathic cystinosis suffer from cystinosis metabolic bone disease (CMBD), related to the renal Fanconi syndrome in infancy and progressive chronic kidney disease (CKD) later in life. Manifestations of CMBD include hypophosphatemic rickets in infancy, and renal osteodystrophy associated with CKD resulting in bone deformities, osteomalacia, osteoporosis, fractures, and short stature. Assessment of CMBD involves monitoring growth, leg deformities, blood levels of phosphate, electrolytes, bicarbonate, calcium, and alkaline phosphatase, periodically obtaining bone radiographs, determining levels of critical hormones and vitamins, such as thyroid hormone, parathyroid hormone, 25(OH) vitamin D, and testosterone in males, and surveillance for nonrenal complications of cystinosis such as myopathy. Treatment includes replacement of urinary losses, cystine depletion with oral cysteamine, vitamin D, hormone replacement, physical therapy, and corrective orthopedic surgery. The recommendations in this article came from an expert meeting on CMBD that took place in Salzburg, Austria, in December 2016. ispartof: JOURNAL OF INHERITED METABOLIC DISEASE vol:42 issue:5 pages:1019-1029 ispartof: location:United States status: published

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.

Epidemiologia; Nefrologia pediàtrica; Registre Epidemiología; Nefrología pediátrica; Registro Epidemiology; Pediatric nephrology; Registry Background The European Rare Kidney Disease Reference Network (ERKNet) recently established ERKReg, a Web-based registry for all patients with rare kidney diseases. The main objectives of this core registry are to generate epidemiological information, identify current patient cohort for clinical research, explore diagnostic and therapeutic management practices, and monitor treatment performance and patient’s outcomes. The registry has a modular design that allows to integrate comprehensive disease-specific registries as extensions to the core database. The diagnosis (Orphacode) and diagnostic information (clinical, imaging, histopathological, biochemical, immunological and genetic) are recorded. Anthropometric, kidney function, and disease-specific management and outcome items informing a set of 61 key performance indicators (KPIs) are obtained annually. Data quality is ensured by automated plausibility checks upon data entry and regular offline database checks prompting queries. Centre KPI statistics and benchmarking are calculated automatically. Results Within the first 24 months since its launch, 7607 patients were enrolled to the registry at 45 pediatric and 12 specialized adult nephrology units from 21 countries. A kidney disease diagnosis had been established in 97.1% of these patients at time of enrolment. While 199 individual disease entities were reported by Orphacode, 50% of the cohort could be classified with 11, 80% with 43 and 95% with 92 codes. Two kidney diagnoses were assigned in 6.5% of patients; 5.9% suffered from syndromic disease. Whereas glomerulopathies (54.8%) and ciliopathies including autosomal dominant polycystic kidney disease (ADPKD) (31.5%) were the predominant disease groups among adults, the pediatric disease spectrum encompassed congenital anomalies of the kidney and urinary tract (CAKUT) (33.7%), glomerulopathies (30.7%), ciliopathies (14.0%), tubulopathies (9.2%), thrombotic microangiopathies (5.6%), and metabolic nephropathies (4.1%). Genetically confirmed diagnoses were reported in 24% of all pediatric and 12% adult patients, whereas glomerulopathies had been confirmed by kidney biopsy in 80.4% adult versus 38.5% pediatric glomerulopathy cases. Conclusions ERKReg is a rapidly growing source of epidemiological information and patient cohorts for clinical research, and an innovative tool to monitor management quality and patient outcomes. Open Access funding enabled and organized by Projekt DEAL. The ERKReg project was made possible by a European Union grant (Chafea #777303) within the Third Health Programme “ERN-2016—Framework Partnership Agreement 2017–2021”. Additional support was received by ERKNet within the same framework. Further support for the development of the registry was kindly provided by the ERA-EDTA Workgroup for Inherited Kidney Diseases (WGIKD).

Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literature search based on the PICO model of clinical questions to formulate educated statements to guide the clinician in the process of decision-making. A set of educated statements on prevention and treatment of FSGS/SRNS after pediatric RTx has been generated after careful evaluation of available evidence and thorough panel discussion. We do not recommend routine nephrectomy prior to transplantation; neither do we recommend abstaining from living donation. Special attendance needs to be given to those patients who had already experienced graft loss due to FSGS/SRNS recurrence. Early PE or IA with or without high-dose CsA and/or rituximab seems to be most promising to induce remission. The educated statements presented here acknowledge that FSGS/SRNS recurrence after pediatric RTx remains a major concern and is associated with shorter graft survival or even graft loss. The value of any recommendation needs to take into account that evidence is based on cohorts that differ in ethnicity, pre-transplant history, immunosuppressive regimen, definition of recurrence (eg, clinical and/or histological diagnosis) and treatment modalities of recurrence.

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.

Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system. A humanised anti-C5 monoclonal antibody (eculizumab) is available for the treatment of aHUS. We present the first description of atypical HUS in a child with a coexistent diagnosis of a POL-III leukodystrophy. On standard eculizumab dosing regime, there was evidence of ongoing C5 cleavage and clinical relapses when immunologically challenged. Eculizumab is an effective therapy for aHUS, but the recommended doses may not be adequate for all patients, highlighting the need for ongoing efforts to develop a strategy for monitoring of treatment efficacy and potential individualisation of therapy.

Background To date, the rare disease research community is largely fragmented in Ireland without a coherent programmatic focus. All too often, priorities for research are decided by one group of stakeholders. The James Lind Alliance (JLA) model allows us to challenge this dynamic through the Rare Disease Research Partnership (RAinDRoP) Workshop which will enable clinicians, patients and carers to work together to identify and prioritise uncertainties that could be answered by research. The RAinDRoP is a truly collaborative effort in which everybody has a voice, and it refocuses the research on the patients rather than the disease. Objectives To identify and prioritise topics and questions in the three research areas: (1) Route to Diagnosis (2) Living with rare diseases (3) Integrated care or Holistic care. Design A modified nominal group technique. Setting Republic of Ireland Participants Anyone with experience of care for patients with rare diseases including patients, carers and healthcare professionals. Results This workshop is scheduled to take place on the 04th of April 2019. The result is not available at the time of submission. Conclusions This study is the first national prioritisation exercise to identify patient and healthcare professional priorities for rare diseases research. The research priority partnership will identify a range of important gaps in the existing evidence to inform (1) Pathway to Diagnosis, focusing on facilitating early, accurate diagnosis and the communication/informational challenges associated with a rare disease diagnosis (2) Supporting management and self-management of rare disease and (3) Integrated care pathways.

Objective Chronic Kidney Disease (CKD) is a debilitating lifelong condition, which can impact many aspects of a person’s life. Experiencing CKD during adolescence is further complicated by the multitude of developmental changes that young people go through at this time period. There is limited research that examines the perspectives of adolescents living with CKD and how they make sense of their experiences. This poster presentation will display/illustrate how adolescents’ use metaphors to narrate their experiences of living with Chronic Kidney Disease. These findings were identified from a qualitative narrative study examining Irish adolescents’ embodied experience of living with CKD. Methods A narrative study using an ethnographic approach was used in this study. Multiple methods were used to engage with five adolescents (10–17 years) living with CKD over an 18-month timeframe in both hospital and home settings. Data was collected from participants through participant observation, informal interviews and participatory methods i.e. body mapping. The collective stories of the adolescents were analysed using Riesman’s approach to narrative analysis. Results The findings of this study reveal that adolescents use visual and textual metaphors as a strategy for communicating the complexities of living with CKD. Within their narratives, adolescents, used scientific metaphors (CKD as a‘black hole’ and ‘atom’), journey metaphors (Orbiting) and supernatural metaphors (alien or vampire) to portray themselves and their condition, and to articulate their experiences in ways that were meaningful to them. Discussion The findings of this study offer a unique contribution to knowledge by highlighting the fact that metaphors are essential to adolescents’ narrations about living with, and communicating about, CKD experiences. Understanding how adolescents communicate about and experience their chronic condition is critical to enable health care providers to appreciate CKD beyond its physical and medical context; thereby providing awareness of the personal implications of chronic disease management on young people’s psychological and social health and wellbeing. These finding have further implications for how health care providers might effectively communicate with adolescents about their personal experiences of living with CKD.

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.

Objective Chronic Kidney Disease (CKD) is a complex disease that requires lifelong treatment. Transplantation is the goal standard treatment, however; it is not without its challenges. While previous research has demonstrated that transplantation increases survival rates and enhances young people’s quality of life, little is known about the impact of kidney transplantation on adolescents’ self-identity development. This presentation will discuss the struggles that adolescent transplant recipients experience as they endeavour to incorporate a new kidney into their embodied self. These findings were identified as a predominant theme from a narrative inquiry of embodiment experiences among young people living with CKD in Ireland. Methods This study employed a narrative inquiry research design. Using an ethnographic approach data were gathered through multi-media approaches including: visual body maps (i.e. life-size human body images), oral informal conversations and observational field notes. Five adolescents (10–17 years) participated in the study, which took place over a period of 18 months as adolescents experienced living with CKD in both hospital and home settings. Results A nuanced finding identified from this study was a disrupted sense of self and identity arising from adolescents’ encounters with a foreign body part (i.e. kidney). Adolescent participants experienced a tension between their body, self and identity as a consequence of transplant surgery. They struggled to adjust to the presence of a foreign organ from a deceased donor and they were concerned about developing personality characteristics of the donor As one participant described, the kidney was not viewed as her own but was conceptualized as ‘a dead persons kidney’. Another participant described the prospective of acquiring the personal qualities or characteristics of the donor as ‘disgusting’. Findings also revealed that adolescents engaged in different individualised ways to cope with the transplanted organ. Discussion The findings from this study provide an understanding of the struggles adolescents endure as they attempt to incorporate a foreign organ within their bodies and the potential impact on their self-identity. Clinicians need to be aware that substituting kidneys with donor organs is much more than a complex technical procedure; it requires an amalgamation of ‘other’ and ‘self’. From a clinical perspective, a multifaceted and holistic person-centred care approach is needed to equip adolescents with the individual skills required to adapt to a new kidney.

Background and aims Our aim is to report the rare Alport syndrome in a mother and daughter. We also wish to highlight the difficulties experienced by Citizens of Ireland when trying to trace birth families in an attempt to obtain medical information necessary for optimum care of their own biological children. Methods We describe the clinical presentation, results of laboratory and radiological investigations and outcome to date of both patients. Results A 6 ½ year-old Irish female presented to our Paediatric Emergency Department with pyrexia, and dysuria. This was on a background history of recurrent urinary tract infections and bilateral sensorineural deafness with cochlear implants placed at 6 months of age by the National Cochlear Implant Programme. Microscopic haematuria and proteinuria were noted on urinary dipstick to which Mum remarked ‘I am also being investigated for blood in my urine’ however, ‘I was adopted and have been unable to find my biological family ‘. Our patient had one older brother. On examination, right sided flank pain and coke coloured urine were noted. Renal ultrasound confirmed right focal pyelonephritis. She was hospitalised and received appropriate antimicrobial therapy with a satisfactory clinical response apart from persistence of hematuria. The context of bilateral sensorineural deafness and associated renal issues with the limited family history cast suspicion of Alport Syndrome. Renal biopsy and genetic testing confirmed this diagnosis. Conclusion This child presented with expressive speech and language delay as an infant. An extensive family history would have facilitated an earlier diagnosis of Alport Syndrome thus improving patient care. Maternal guilt due to limited family knowledge and management of patient and parental anxiety were apparent. Finally, this case demonstrates the limited services available in Ireland for tracing lineage for adoptees such as the Adoption Authority and Private Investigators, bridging on the conversation of the right to privacy verses patient care.

BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft failure, but large-scale data in pediatric renal transplant recipients and a comprehensive analysis of specific risk factors are lacking.We analyzed the data of 313 patients in the Cooperative European Pediatric Renal Transplant Initiative Registry, with an observation period of 3.3 years (range, 1-5). The net state of immunosuppressive therapy was assessed by the modified Vasudev score.Presumptive BKPyVAN (defined as sustained [3 wk] high-level BK viremia10 copies/mL) within 5 years posttransplant occurred in 49 (15.8%) of 311 patients, and biopsy-proven BKPyVAN in 14 (4.5%) of 313. BKPyV viremia was observed in 115 (36.7%) of 311 patients, of whom 11 (9.6%) of 115 developed viremia late, that is, after the second year posttransplant. In 6 (12.5%) of 48 patients with high-level viremia and in 3 (21.4%) of 14 with BKPyVAN, this respective event occurred late. According to multivariable analysis, BKPyV viremia and/or BKPyVAN were associated not only with a higher net state of immunosuppression (odds ratio [OR], 1.3; P0.01) and with tacrolimus-based versus ciclosporin-based immunosuppression (OR, 3.6; P0.01) but also with younger recipient age (OR, 1.1 per y younger; P0.001) and obstructive uropathy (OR, 12.4; P0.01) as primary renal disease.Uncontrolled BKPyV replication affects a significant proportion of pediatric renal transplant recipients and is associated with unique features of epidemiology and risk factors, such as young recipient age, obstructive uropathy, and overall intensity of immunosuppressive therapy. BKPyV surveillance should be considered beyond 2 years posttransplant in pediatric patients at higher risk.

Monitoring of Epstein-Barr virus DNA viral loads (EBVL) in whole blood and plasma following pediatric kidney transplantation has been routinely employed to facilitate the diagnosis and management of Epstein-Barr virus (EBV) infection. However, recent studies from our laboratory and others have demonstrated a number of transplant recipients with chronically high EBVL, thereby calling into question the clinical utility of monitoring EBVL. The aim of this study was to compare the relative diagnostic value of measuring EBV DNA load in plasma and whole blood collected in parallel from 64 pediatric kidney transplant recipients. Thirteen patients had a high EBVL and were characterised in detail and 11 (84.6%) of these were EBV seronegative at the time of kidney transplant. It has been hypothesised that the point immediately before EBV seroconversion can be identified by a peak in plasma EBVL. However, compared to plasma, whole blood EBVL remained fairly constant over time for these patients. Overall, a correlation was observed between whole blood and plasma EBVL in sequential specimens collected post-transplant (r=-0.95, p

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.

Introduction Primary focal segmental glomerular sclerosis (p-FSGS) is commonly complicated by recurrence (r-FSGS) post-transplantation. Our objective was to describe Irish outcomes for transplantation after ESRD due to p-FSGS, specifically rates of, and treatments for, r-FSGS. Patients and Methods Irish patients with biopsy proven FSGS were identified from the Irish National Kidney Transplant database (1982-2015). Medical record review was performed to identify predictors of r-FSGS and treatments for r-FSGS. Transplant outcomes were compared to outcomes in all renal transplants performed during the same time period using registry data. Demographic and clinical predictors of r-FSGS were identified. Statistical analysis was performed using Stata (version 13, College Station, Texas). Results 38 transplant recipients had biopsy-proven p-FSGS, 16 received a second transplant. 3846 transplants formed the comparator group. r-FSGS complicated 60.5% (23/38) of first transplants. 86% (10/12) of patients with previous r-FSGS developed recurrent disease after further transplantation. Patients with p-FSGS receiving a first renal transplant had higher rate of graft failure than those with another cause of ESRD (HR 1.9, 95% CI 1.152-3.139). 16 patients received immunotherapy for r-FSGS; 12 (86%) had at least partial response but two (14%) developed significant complications. Discussion We demonstrate high rates of r-FSGS and describe modest success from with treatments for r-FSGS. This article is protected by copyright. All rights reserved.

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.

BACKGROUND Studies have identified solid organ transplant recipients who remain asymptomatic despite maintaining chronic high Epstein-Barr virus (EBV) viral loads. We examined clinical manifestations, EBV gene expression, human leukocyte antigen (HLA) alleles, and specific T-cell responses to EBV infection in pediatric renal transplant patients. METHODS Seventeen pediatric renal transplant patients were categorized according to EBV viral load into those with chronic high viral loads (CHL) and recipients who resolve EBV infection (REI). EBV gene expression was analyzed using real-time PCR assays and EBV-specific T cells were analyzed by flow cytometry. RESULTS EBV gene, EBV-encoded small RNA 1, was expressed at significantly higher levels in CHL compared with EBV seropositive controls (P=0.005) and raised compared with REI. BamHI A right-ward transcripts were also expressed at higher levels in CHL patients (P=0.03) than in REI. Expression of latent genes, EBNA1, LMP1, LMP2, and lytic gene BZLF1 were restricted to the CHL group with viral gene expression varying over time. HLA-A*02 allele expression was predominant in CHL patients (80%) and GLC lytic-specific cytotoxic T-lymphocytes were absent. In contrast, HLA-B*08 allele expression was prevalent in REI patients (71%) and RAK lytic cytotoxic T-lymphocytes were detected in all patients. CONCLUSION EBV gene expression in CHL carriers differs from those that resolve infection and should be interpreted alongside HLA polymorphisms.

Raheem OA, Kamel MH, Daly PJ, Mohan P, Little DM, Awan A, Hickey DP. Mycophenolate mofetil in pediatric renal transplantation: A single center experience. Pediatr Transplantation 2011: 15:240–244. © 2009 John Wiley & Sons A/S. Abstract: We assessed our long-term experience with regards to the safety and efficacy of MMF in our pediatric renal transplant population and compared it retrospectively to our previous non-MMF immunosuppressive regimen. Forty-seven pediatric renal transplants received MMF as part of their immunosuppressive protocol in the period from January 1997 till October 2006 (MMF group). A previously reported non-MMF group of 59 pediatric renal transplants was included for comparative analysis (non-MMF group). The MMF group comprised 29 boys and 18 girls, whereas the non-MMF group comprised 34 boys and 25 girls. Mean age was 11.7 and 12 yr in the MMF and non-MMF groups, respectively. The incidence of acute rejection episodes was 11 (23.4%) and 14 (24%) in the MMF and non-MMF group, respectively. Two (3.3%) grafts were lost in the non-MMF group compared with one (2.1%) in the MMF group. Twenty-one (44.68%) patients in the MMF group developed post-transplant infections compared with 12 (20.33%) in the non-MMF group (p

We report two cases of non-cardiogenic pulmonary edema as a complication of basiliximab induction therapy in young pediatric renal transplant patients identified following a retrospective review of all pediatric renal transplant cases performed in the National Paediatric Transplant Centre, Childrens University Hospital, Temple Street, Dublin, Ireland. Twenty-eight renal transplantations, of which five were living-related (LRD) and 23 were from deceased donors (DD), were performed in 28 children between 2003 and 2006. In six cases, transplantations were pre-emptive. Immunosuppression was induced pre-operatively using a combination of basiliximab, tacrolimus and methylprednisolone in all patients. Basiliximab induction was initiated 2 h prior to surgery in all cases and, in 26 patients, basiliximab was re-administered on post-operative day 4. Two patients, one LRD and one DD, aged 6 and 11 years, respectively, developed acute non-cardiogenic pulmonary edema within 36 h of surgery. Renal dysplasia was identified as the primary etiological factor for renal failure in both cases. Both children required assisted ventilation for between 4 and 6 days. While both grafts had primary function, the DD transplant patient subsequently developed acute tubular necrosis and was eventually lost within 3 weeks due to thrombotic microangiopathy and severe acute antibody-mediated rejection despite adequate immunosuppression. Non-cardiogenic pulmonary edema is a potentially devastating post-operative complication of basiliximab induction therapy in young pediatric patients following renal transplantation. Early recognition and appropriate supportive therapy is vital for patient and, where possible, graft survival.

Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were tested (odds ratio, 2.11; 95% confidence interval, 1.56 to 2.86; P=1.68×10(-6) (Fisher exact test). Two of these SNPs-the missense variants C34Y (rs1129740) and F41S (rs1071630) in HLA-DQA1-were replicated in an independent cohort of children of white European ancestry with SSNS (100 cases and ≤589 controls; P=1.42×10(-17)). In the rare variant gene set-based analysis, the best signal was found in PLCG2 (P=7.825×10(-5)). In conclusion, this exome array study identified HLA-DQA1 and PLCG2 missense coding variants as candidate loci for SSNS. The finding of a MHC class II locus underlying SSNS risk suggests a major role for immune response in the pathogenesis of SSNS.

Proton pump inhibitors (PPIs) have emerged as a common cause of drug induced acute interstitial nephritis (AIN) in adults. We present a 15-year-old girl with severe acute kidney injury and biopsy proven AIN attributable to omeprazole. Withdrawal of the drug and steroid therapy affected a recovery of renal function. As the use of PPIs increases in paediatrics, it is important to be aware of this rare but serious side effect.

There have been few reported cases of cyanide toxicity following treatment with sodium nitroprusside. We report on the case of a paediatric patient who had received sodium nitroprusside for intractable hypertension in the post-operative period, resulting in cyanide toxicity. Treatment with sodium thiosulphate, sodium nitrate and haemodialysis resulted in the elimination of cyanide from the circulation. The patient made a full recovery with no neurological sequelae.

Summary Background and objectives The term C3 glomerulopathy describes renal disorders characterized by the presence of glomerular deposits composed of C3 in the absence of significant amounts of Ig. On the basis of electron microscopy appearance, subsets of C3 glomerulopathy include dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). The full spectrum of histologic change observed in C3 glomerulopathy has yet to be defined and pathologic predictors of renal outcome within this patient population remain largely unknown. This study thus characterized a large C3 glomerulopathy cohort and identified clinicopathologic predictors of renal outcome. Design, setting, participants, & measurements All patients with kidney biopsies fulfilling criteria for C3 glomerulopathy from two quaternary renal centers within the United Kingdom and Ireland between 1992 and 2012 were retrospectively reviewed. We recorded histologic, demographic, and clinical data and determined predictors of ESRD using the Cox proportional hazards model. Results Eighty patients with C3 glomerulopathy were identified: 21 with DDD and 59 with C3GN. Patients with DDD were younger, more likely to have low serum C3 levels, and more likely to have crescentic GN than patients with C3GN. Patients with C3GN were older and had more severe arteriolar sclerosis, glomerular sclerosis, and interstitial scarring than patients with DDD. Of 70 patients with available follow-up data, 20 (29%) progressed to ESRD after a median of 28 months. Age >16 years, DDD subtype, and crescentic GN were independent predictors of ESRD within the entire cohort. Renal impairment at presentation predicted ESRD only among patients with DDD. Conclusions Although detailed serologic and genetic data are lacking, this study nevertheless identifies important clinicopathologic distinctions between patients with DDD and C3GN. These include independent predictors of renal outcome. If replicated in other cohorts, these predictors could be used to stratify patients, enabling application of emerging mechanism-based therapies to patients at high risk for poor renal outcome.