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Cancer and its treatment may lead to kidney injury and the need for kidney replacement therapy (KRT). We identified 287 pediatric KRT patients with a history of malignancy from the European Society for Paediatric Nephrology/European Renal Association Registry. Of these, 197 had cancer as a primary cause of KRT (group 1) and 90 had a malignancy diagnosis before KRT (group 2). Two matched controls without malignancy were randomly selected for each patient. Data were complemented with a questionnaire. Median time to kidney transplantation (KT) from KRT initiation was 2.4 (IQR: 1.5-4.7), 1.5 (IQR: 0.4-3.3), 3.6 (IQR: 1.3 to Q3 not reached), and 1.1 (IQR: 0.3-3.6) years for group 1, their controls, group 2, and their controls, respectively. Overall 10-year mortality for those on KRT was higher among cancer patients vs controls in group 1: 16% vs 9% (adjusted hazard ratio 2.02, 95% CI: 1.21-3.37) and in group 2: 23% vs 14% (adjusted hazard ratio 2.32, 95% CI: 1.11-4.85). In contrast, 10-year patient survival after the first KT was comparable to controls (93% vs 96%; 100% vs 94%, in groups 1 and 2, respectively). In summary, childhood cancer survivors' KT was delayed, and their overall mortality when on KRT was increased, but once transplanted, their long-term outcome was similar to other KT recipients., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: There have been no longitudinal studies examining the evolution of psychosocial health of young adults with kidney failure as they age. We aimed to address this in the Surveying Patients Experiencing Young Adult Kidney Failure-2 (SPEAK-2) study., Study Design: 5-year follow-up longitudinal survey of the original SPEAK cohort., Setting & Participants: 16- to 30-year-olds in the UK receiving kidney replacement therapy (KRT) between 2015 and 2017 who participated in the SPEAK study., Exposure: Kidney failure and KRT modality., Outcomes: Psychosocial health and lifestyle behaviors., Analytical Approach: Within-cohort changes in psychosocial health were analyzed using the paired t test, Wilcoxon signed-rank test and McNemar's test. We compared responses to the age-matched population and examined the impact of changes in KRT modality on psychological health using linear regression for continuous outcome variables as well as logistic, ordered logistic and multinomial logistic regression for binary, ordered categorical and unordered categorical variables, respectively., Results: We obtained 158 survey responses; 129 had previously responded to SPEAK. Of these, 90% had a kidney transplant. Compared to the general population, respondents were less likely to be married or have children and were more likely to be living with their parents. Respondents had nearly 15 times greater odds of being unable to work due to health (odds ratio [OR] = 14.41; 95% confidence interval [CI], 8.0-26.01; P  < 0.001). Respondents had poorer quality of life and mental wellbeing and were more likely to report psychological problems (OR = 5.37; 95% CI, 3.45-8.35; P  < 0.001). A negative association between remaining on or moving to dialysis and psychosocial health was observed, although this was attenuated when controlling for the psychosocial state in SPEAK., Limitations: Low response rate resulting in imprecise and potentially biased estimates and impact of COVID-19 pandemic while survey was active on psychosocial health., Conclusions: Young adults with kidney failure have persistent poorer psychosocial health compared to their healthy peers as they age. Our findings also suggest a potential causal relationship between KRT modality and psychosocial health., (© 2023 The Authors.)

Haemolytic uraemic syndrome (HUS) caused by infection with Shiga toxin-producing Escherichia coli (STEC) is a relatively rare but potentially fatal multisystem syndrome clinically characterised by acute kidney injury. This study aimed to provide robust estimates of paediatric HUS incidence in England, Wales, Northern Ireland, and the Republic of Ireland by using data linkage and case reconciliation with existing surveillance systems, and to describe the characteristics of the condition. Between 2011 and 2014, 288 HUS patients were included in the study, of which 256 (89.5%) were diagnosed as typical HUS. The crude incidence of paediatric typical HUS was 0.78 per 100,000 person-years, although this varied by country, age, gender, and ethnicity. The majority of typical HUS cases were 1 to 4 years old (53.7%) and female (54.0%). Clinical symptoms included diarrhoea (96.5%) and/or bloody diarrhoea (71.9%), abdominal pain (68.4%), and fever (41.4%). Where STEC was isolated (59.3%), 92.8% of strains were STEC O157 and 7.2% were STEC O26. Comparison of the HUS case ascertainment to existing STEC surveillance data indicated an additional 166 HUS cases were captured during this study, highlighting the limitations of the current surveillance system for STEC for monitoring the clinical burden of STEC and capturing HUS cases.

The UK Renal Registry currently collects information on UK children with kidney failure requiring long-term kidney replacement therapy (KRT), which supports disease surveillance and auditing of care and outcomes; however, data are limited on children with chronic kidney disease (CKD) not on KRT., Methods: In March 2020, all UK Paediatric Nephrology centres submitted data on children aged <16 years with severely reduced kidney function as of December 2019, defined as an estimated glomerular filtration rate <30 mL/min/1.73 m 2 ., Results: In total, 1031 children had severe CKD, the majority of whom (80.7%) were on KRT. The overall prevalence was 81.2 (95% CI 76.3 to 86.3) per million of the age-related population., Conclusions: The prevalence of severe CKD among UK children is largely due to a high proportion of children on long-term KRT. Expanding data capture to include children with CKD before reaching failure will provide greater understanding of the CKD burden in childhood., Competing Interests: Competing interests: LP declares funding from the National Institute for Health Research (NIHR) and Kidney Research UK (KRUK). BCR declares funding from KRUK, honoraria from Alexion Pharmaceuticals and Magnolia Innovation, and consultancy payment from Chiesi. MM reports previous honoraria and travel expenses from Alexion. SM declares a role as head of the UK Renal Registry Audit and Informatics group. KT declares a role as clinical lead of the National Institute for Health and Care Excellence Medical Technologies Advisory Committee during the study period. DN declares funding/payment from the Health Foundation, UK Kidney Association, Chiang Mai University and GSK., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The UK Renal Registry is responsible for the national collection and reporting of data on all children receiving long-term kidney replacement therapy [KRT], including kidney transplantation., Methods: All 13 UK pediatric nephrology centers contributed to providing individual patient data from the pediatric population incident to and prevalent to KRT as per the date 31 December 2018. Data for children aged 16-<18 years were presented separately as some were managed under adult care settings with different methods of data collection. Demographics and biochemical data, including kidney function and prevalence of cardiovascular risk factors [hypertension, hypercholesterolemia, BMI] were reported., Results: Eight hundred and twenty-six children (65.4 per million age-related population [pmarp]) and 199 young people (139.4pmarp) in the United Kingdom were prevalent to KRT on 31 December 2018. Overall, the incidence of KRT during 2018 was 9.1 pmarp and 12.6 pmarp in children and young people, respectively. Congenital anomalies of the kidney and urinary tract (CAKUT) were the most prevalent primary diagnoses (52%). Living and deceased donor transplantation was the most common treatment modality (78%). Patients on dialysis had lower age standardized mean height and weight ranges recorded in comparison to transplant patients [median height z score -1.8 vs. -1.1]. 73.1% patients had one or more cardiovascular disease risk factors., Conclusions: This study highlights increasing prevalence of hemodialysis and living donor transplantation as modalities for KRT. Of those incident to KRT, the highest patient survival was seen among 8-12 years and lowest <2 years. Moreover, there was a demographic shift from Caucasian toward Asian/other ethnicity and from CAKUT to other primary kidney diseases., (© 2022 Wiley Periodicals LLC.)

Aims: To investigate access to paediatric renal transplantation and examine potential barriers within the process., Methods: Cross-sectional, multicentre, observational study where paediatric nephrology centres in the UK were requested to provide data on transplantation plans for all children (<18 years) with end-stage kidney disease (ESKD)., Results: 308 children with ESKD were included in this study from 12 out of 13 UK paediatric nephrology centres. 139 (45%) were being prepared for living donor transplantation and 82 (27%) were listed for deceased donor transplantation. The most common cited factors delaying transplantation from occurring in children were disease factors (36%), donor availability (27%) and size of the child (20%). Psychosocial factors were listed as a barrier in 19% of children., Conclusions: In this study we have documented the main barriers to renal transplantation in children. Some identified factors may be modifiable through local or national intervention, including donor availability and patient psychosocial factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Recessive mutations in diacylglycerol kinase epsilon (DGKE) display genetic pleiotropy, with pathological features reported as either thrombotic microangiopathy or membranoproliferative glomerulonephritis (MPGN), and clinical features of atypical hemolytic uremic syndrome (aHUS), nephrotic syndrome or both. Pathophysiological mechanisms and optimal management strategies have not yet been defined. In prospective and retrospective studies of aHUS referred to the United Kingdom National aHUS service and prospective studies of MPGN referred to the National Registry of Rare Kidney Diseases for MPGN we defined the incidence of DGKE aHUS as 0.009/million/year and so-called DGKE MPGN as 0.006/million/year, giving a combined incidence of 0.015/million/year. Here, we describe a cohort of sixteen individuals with DGKE nephropathy. One presented with isolated nephrotic syndrome. Analysis of pathological features reveals that DGKE mutations give an MPGN-like appearance to different extents, with but more often without changes in arterioles or arteries. In 15 patients presenting with aHUS, ten had concurrent substantial proteinuria. Identified triggering events were rare but coexistent developmental disorders were seen in six. Nine with aHUS experienced at least one relapse, although in only one did a relapse of aHUS occur after age five years. Persistent proteinuria was seen in the majority of cases. Only two individuals have reached end stage renal disease, 20 years after the initial presentation, and in one, renal transplantation was successfully undertaken without relapse. Six individuals received eculizumab. Relapses on treatment occurred in one individual. In four individuals eculizumab was withdrawn, with one spontaneously resolving aHUS relapse occurring. Thus we suggest that DGKE-mediated aHUS is eculizumab non-responsive and that in individuals who currently receive eculizumab therapy it can be safely withdrawn. This has important patient safety and economic implications., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange-treated patients was not adopted due to concerns over treatment-associated complications. Without immunosuppression, the relapse rate was high (five of seven). However, reintroduction of treatment resulted in recovery of renal function. All patients treated with eculizumab achieved sustained remission. Five patients received renal transplants without specific factor H autoantibody-targeted treatment with recurrence in one who also had a functionally significant CFI mutation. Thus, our current practice is to initiate eculizumab therapy for treatment of factor H autoantibody-mediated atypical hemolytic uremic syndrome rather than plasma exchange with or without immunosuppression. Based on this retrospective analysis we see no suggestion of inferior treatment, albeit the strength of our conclusions is limited by the small sample size., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: We evaluated rates and factors associating with late referral (LR) and describe association of LR with access to renal transplantation and patient survival in children in the United Kingdom. Early requirement of RRT within 90 days of presentation to a pediatric nephrologist was classed as a LR, and those >90 days as an early referral (ER)., Design, Setting, Participants, & Measurements: We included patients who commenced RRT, aged ≥3 months and <16 years, from 1996 to 2012., Results: Of 1603 patients, 25.5% (n=408) were LR, of which 75% commenced RRT in <30 days following presentation. Those with LR were more likely to be older at presentation, female, and black. The primary renal disease in LR was more likely to be glomerular disease (odds ratio [OR], 1.6; 95% confidence interval [95% CI], 1.12 to 2.29), renal malignancy and associated diseases (OR, 4.11; 95% CI, 1.57 to 10.72), tubulo-interstitial diseases (OR, 2.37; 95% CI, 1.49 to 3.78), or an uncertain renal etiology (OR, 5.75; 95% CI, 3.1 to 10.65). Significant differences in rates of transplantation between LR and ER remained up to 1-year following commencement of dialysis (21% versus 61%, P<0.001) but with no differences for donor source (33.3% and 35.3% living donor in LR and ER respectively, P=0.55). The median (interquartile range) follow-up time was 4.8 years (2.9-7.6). There were 55 deaths with no statistically significant difference in survival in the LR group compared with the ER group (hazard ratio, 1.30; 95% CI, 0.7 to 2.3; P=0.40)., Conclusions: We found that 25% of children starting RRT in the United Kingdom receive a LR to pediatric renal services, with little change observed over the past two decades. Those with LR are unable to benefit from pre-emptive transplantation and require longer periods of dialysis before transplantation. There is an urgent need to understand causes of avoidable LR and develop strategies to improve kidney awareness more widely among health care professionals looking after children., (Copyright © 2016 by the American Society of Nephrology.)

Background: Paediatric renal biopsy standards introduced in the UK in 2010 were intended to reduce variation and improve practice. A concurrent national drive was aimed at building robust paediatric nephrology networks to ensure services cater for the needs of the family and minimise time away from home. We aimed to identify current national practice since these changes on behalf of the British Association for Paediatric Nephrology., Methods: All UK paediatric nephrology centres were invited to complete a survey of their biopsy practice, including advance preparation. From 1 January to 30 June 2012, a national prospective audit of renal biopsies was undertaken at participating centres comparing practice with the British Association for Paediatric Nephrology (BAPN) standards and audit results from 2005., Results: Survey results from 11 centres demonstrated increased use of pre-procedure information leaflets (63.6 % vs 45.5 %, P = 0.39) and play preparation (90.9 % vs 9.1 %, P = 0.0001). Audit of 331 biopsies showed a move towards day-case procedures (49.5 % vs 32.9 %, P = 0.17) and reduced major complications (4.5 % vs 10.4 %, P = 0.002). Biopsies with 18-gauge needles had significantly higher mean pass rates (3.2 vs 2.3, P = 0.0008) and major complications (15.3 % vs 3.3 %, P = 0.0015) compared with 16-gauge needles., Conclusions: Percutaneous renal biopsy remains a safe procedure in children, thus improving family-centered service provision in the UK.

The median height z-score for paediatric patients on dialysis was −2.1 and for those with a functioning transplant −1.3. Children transplanted before the age of 12 years improved their height z-score over the subsequent five years, whereas those older than 12 maintained their height z-score, with all transplanted patients having a similar median height z-score after five years of starting renal replacement therapy (RRT). The median weight z-score for children on dialysis was −1.4 whereas children with a functioning transplant had a near normal weight for age and sex with a median z-score of −0.3. Of those with data, 75% of the prevalent paediatric RRT population had one or more ‘traditional’ risk factors for cardiovascular disease, with 1 in 10 having all three risk factors present. For the 10 centres reporting quarterly laboratory data, the average creatinine in transplant patients was 79 mmol/L; dialysis patients had normal average anaemia and acidosis markers and evidence of secondary hyperparathyroidism with an average PTH of 17.3 pmol/L. For transplant patients, 80% achieved the systolic blood pressure (SBP) standard and 93% achieved the haemoglobin standard. For haemodialysis patients, 57% achieved the SBP standard, 62% achieved the haemoglobin standard, 82% achieved the calcium standard, 51% achieved the phosphate standard and 39% achieved the parathyroid hormone (PTH) standard. For peritoneal dialysis patients, 70% achieved the SBP standard, 77% achieved the haemoglobin standard, 72% achieved the calcium standard, 54% achieved the phosphate standard and 33% achieved the PTH standard.

A total of 917 children and young people under 18 years with established renal failure (ERF) were receiving treatment at paediatric nephrology centres in 2014.At the census date (31st December 2014), 79.3% of prevalent paediatric patients aged ,18 years had a functioning kidney transplant, 11.2% were receiving haemodialysis (HD) and 9.5% were receiving peritoneal dialysis (PD). In patients aged ,16 years, prevalence of ERF was 60.4 per million age related population (pmarp) and the incidence 9.4 pmarp. The most common primary renal diagnosis was renal dysplasia+reflux, present in 32.6% of prevalent paediatric patients aged ,16 years. About a third of patients had one or more reported comorbidity at onset of renal replacement therapy (RRT). The improvement in rates of pre-emptive transplantation for those referred early has been maintained over the last 10 years at 37.5%, compared to 27.4% in 2000–2004. At transfer to adult services, 90.3% of patients had a functioning kidney transplant. Survival during childhood amongst children commencing RRT was the lowest in those aged less than two years compared to those aged 12 to less than 16 years with a hazard ratio of 4.1 (confidence interval 2.2–8.0), and in those receiving dialysis compared to having a functioning transplant with a hazard ratio of 6.3 (confidence interval 3.9–10.2).

Aims: To describe the demographics of the paediatric renal replacement therapy (RRT) population under the age of 18 years in the UK and to analyse changes in demography over time., Methods: Data were collected electronically from all 13 paediatric renal centres within the UK. A series of cross-sectional and longitudinal analyses were performed to describe the demographics of paediatric RRT patients., Results: A total of 891 children and young people under 18 with established renal failure (ERF) were receiving treatment at paediatric nephrology centres in 2013. At the census date, 80.2% had a functioning transplant, 11.7%were receiving haemodialysis (HD) and 8.1% were receiving peritoneal dialysis (PD). In patients aged ,16 years the prevalence of ERF was 58.2 per million age related population(pmarp) and the incidence 9.3 pmarp. A third of the prevalent patients had one or more reported comorbidities.At transfer to adult services, 85.2% of patients had a functioning renal transplant. Pre-emptive transplantation was seen to occur in a third of children starting RRT under16 years, with lower rates seen in girls and ethnic minorities.Living donation as starting modality has continued to improve with an increase from 8.8% in 1999–2003 to 18.4% in 2009–2013. Survival in childhood amongst children starting RRT was the lowest in those aged less than two years., Conclusions: We report continued improvement in data quality and electronic submission of data returns. The data provided in this report show relatively stable trends of incidence and prevalence in children with established renal failure.

Background: The Paediatric Registry analyses renal replacement therapy (RRT) data in children. All 13 UK paediatric nephrology centres submit electronic data., Aims: To provide centre specific data and to determine adherence to relevant audit standards., Methods: Data analysis to calculate summary statistics and achievement of an audit standard., Results: The median height z-score for children on dialysis was -2.0 and for children with a functioning transplant -1.3. Children transplanted before age 11 years improved their height z score subsequently, whereas those >11 maintained their height z-score, with all transplanted patients having a similar height z-score after 3 years of starting RRT.The median weight z-score for children on dialysis was -1.2, and for children with a functioning transplant -0.2.Of those with data, 75% of the prevalent paediatric RRT population had .1 risk factors for cardiovascular disease, with 1 in 10 having all three risk factors evaluated. For transplant patients, 76% achieved the systolic blood pressure (SBP)standard and 91% achieved the haemoglobin standard. For haemodialysis patients, 53% achieved the SBP standard,66% the haemoglobin standard, 84% the calcium standard,43% the phosphate standard and 43% achieved the parathyroid hormone (PTH) standard. For peritoneal dialysis patients, 61% achieved the SBP standard, 83% the haemoglobin standard, 71% the calcium standard, 56% the phosphate standard and 36% achieved the PTH standard., Conclusions: Quarterly data collection will improve quality and reporting. Continued focus on improving height and avoiding obesity is needed. Awareness and management of cardiovascular risk is an important long term strategy.

End-stage renal disease requiring renal replacement therapy (RRT) during the neonatal period is a very rare condition, and little information is available regarding long-term RRT and outcomes. To gain more information, we performed a collaborative study on patient characteristics and treatment outcomes in children who started RRT as neonates during their first month of life between 2000 and 2011 who were prospectively registered in the ESPN/ERA-EDTA, the IPPN (since 2007), the Japanese registry, or the Australian and New Zealand Dialysis and Transplant (ANZDATA) registry. During the first month of life, 264 patients from 32 countries started RRT and were followed for a median of 29 months (interquartile range 11-60 months). Most neonates (242) started on peritoneal dialysis, 21 started on hemodialysis, and 1 patient with a transplant. The most important causes of renal failure were congenital anomalies of the kidney and urinary tract in 141, cystic kidneys in 35, and cortical necrosis in 30. Within 2 years after the start of RRT, 69 children changed dialysis modality and 53 received a renal transplant. After a median of 7 months, 45 children had died, mainly because of infection, resulting in an estimated 2-year survival of 81%, and 5-year survival of 76%. Growth retardation (63%), anemia (55%), and hypertension (57%) were still major problems after 2 years. Thus, relatively good medium-term patient survival may be achieved with RRT started during the neonatal period, but specific therapeutic challenges continue to exist in this age group.

Background: Childhood obesity is a significant health problem in the UK. To date, there is little known about the pattern of change in body mass index (BMI) following renal transplantation in UK paediatric patients. Our objectives in this study were to (i) describe trends in BMI seen in UK patients undergoing renal transplantation in the short and medium term and (ii) identify risk factors predisposing children to excessive weight gain following transplantation., Methods: A retrospective case note review was performed across 12 of 13 paediatric nephrology centres in the UK, with BMI measurements recorded pre-transplantation and for 4 years thereafter. BMI% was used to assess changes in adiposity over time. International Obesity Taskforce definitions of overweight and obesity were used to identify the prevalence of excess weight pre- and post-renal transplantation., Results: A total of 159 patients (113 boys) under the age of 18 with a functioning kidney transplant were included. Fifty-six patients (35.2%) were under the age of 5 at transplantation. Pre-transplantation, 31.4% of patients were classified as overweight or obese, which increased to 52.8% by the end of follow-up. The majority of patients experienced rapid increases in BMI% over the initial four months post-transplantation, which were sustained for the remainder of the follow-up period. The major risk factor for being overweight or obese at the end of follow-up was having excessive weight pre-transplantation. Four years following transplantation, the prevalence rate of overweight and obesity was much higher in our study cohort than the normal UK childhood population., Conclusions: The prevalence of patients classified as overweight or obese in the UK paediatric renal cohort is high pre-transplantation and rises subsequently. Those at risk can be identified by an unhealthy BMI pre-transplantation and will require timely intervention with close monitoring in the subsequent post-transplantation period.

Aims: To describe the demographics of the paediatric RRT population under the age of 16 years in the UK and to analyse changes in demography with time., Methods: Data were collected from all 13 paediatric renal centres within the UK. A series of cross-sectional and longitudinal analyses were performed to describe the demographics of paediatric RRT patients., Results: A total of 856 children and young people under 18 with ERF were receiving treatment at paediatric nephrology centres in 2011. At the census date, 80.1% had a functioning transplant, 10.5% were receiving peritoneal dialysis (PD) and 9.4% were receiving haemodialysis (HD). In patients aged <16 years the prevalence of ERF was 56.8 pmarp and the incidence 8.3 pmarp. Analysis of trends over the last 15 years shows that both incidence and prevalence are increasing. A third of the prevalent patients had one or more reported comorbidities. At transfer to adult services, 86% of patients had a functioning renal transplant. Pre-emptive transplantation was seen to occur in 31% of children starting RRT under 16 years, with lower rates seen in girls and ethnic minorities. Survival in childhood amongst children starting RRT was the lowest in those aged less than 2 years., Conclusions: The data provided in this report show increasing trends over 15 years in the incidence and prevalence of established renal failure. This is important for the planning of the provision of care for children needing renal replacement therapy. Further research is required to understand the gender and ethnic differences in pre-emptive transplantation rates and the reduced survival amongst children aged less than 2 years., (Copyright © 2013 S. Karger AG, Basel.)

Background: The British Association for Paediatric Nephrology Registry was established to analyse data related to renal replacement therapy (RRT) in children. The registry receives data from the 13 paediatric nephrology centres in the UK., Aims: To provide centre specific data so that individual centres can reflect on the contribution that their data makes to the national picture and to determine the extent to which their patient parameters meet nationally agreed audit standards for the management of children with established renal failure., Methods: Data returns have been a mixture of electronic and paper returns. Data were analysed to calculate summary statistics and where applicable the percentage achieving an audit standard. The standards used were those set out by the Renal Association and the National Institute for Health and Clinical Excellence., Results: Anthropometric data confirmed that children receiving RRT were short compared to healthy peers. Amongst patients with a height of <2 SD between 2001 and 2011, 31% were receiving growth hormone if they were on dialysis compared to 10% if they had a functioning transplant. Blood pressure control remained challenging with wide inter-centre variation although this was significantly better in children with a functioning transplant. Over a third of haemodialysis patients and a quarter of peritoneal dialysis patients were anaemic, compared to only 7% of transplanted patients. ESA use in the dialysis population exceeded 90% amongst anaemic patients. The control of renal bone disease remained challenging., Conclusions: Optimizing growth in children on RRT remained challenging and the control of bone biochemistry in children on dialysis was imperfect. The likelihood of complete electronic reporting in the near future with plans for quarterly reporting in the format of the recently finalised NEW paediatric dataset will hopefully improve quality of data and their reporting, allowing improvements in patient care., (Copyright © 2013 S. Karger AG, Basel.)

Introduction: The British Association for Paediatric Nephrology Registry (BAPN) was established to analyse data related to renal replacement therapy (RRT) in children. The registry receives data from the 13 paediatric nephrology centres in the UK. This chapter aims to provide centre specific data so that individual centres can reflect on the contribution that their data makes to the national picture and to determine the extent to which their patient parameters meet nationally agreed audit standards for the management of children with established renal failure (ERF)., Methods: Data returns included a mixture of electronic (92%) and paper (8%) returns. Data were analysed to calculate summary statistics and where applicable the percentage achieving an audit standard. The standards used were those set out by the Renal Association and the National Institute for Health and Clinical Excellence., Results: Anthropometric data confirmed that children receiving RRT were short compared to healthy peers. Amongst patients with a height of <2SD between 2001 and 2012, 29.2%were receiving growth hormone if they were on dialysis compared to 11.9% if they had a functioning transplant. Prevalence rates of overweight and obese status in children with ERF remain concerningly high. Blood pressure control remained challenging with wide inter-centre variation although this was significantly better in children with a functioning transplant. Over a quarter of haemodialysis patients and 17.3% of peritoneal dialysis patients were anaemic, compared to only 8.3% of transplanted patients. ESA use in the dialysis population exceeded 90% amongst anaemic patients. The control of renal bone disease remained challenging., Conclusions: Optimising growth and reducing prevalent excess weight in children on RRT remains challenging. The likelihood of complete electronic reporting in the near future with plans for quarterly reporting in the format of the recently finalised NEW paediatric dataset will hopefully improve quality of data and their reporting, allowing improvements in patient care., (© 2014 S. Karger AG, Basel.)

Introduction: To describe the demographics of the paediatric renal replacement therapy (RRT) population under the age of 18 years in the UK and to analyse changes in demography with time., Methods: Data were collected from all 13 paediatric renal centres within the UK. A series of crosssectional and longitudinal analyses were performed to describe the demographics of paediatric RRT patients., Results: A total of 861 children and young people under 18 with established renal failure (ERF) were receiving treatment at paediatric nephrology centres in 2012. At the census date, 80.2% had a functioning transplant, 10.6% were receiving haemodialysis (HD) and 9.2% were receiving peritoneal dialysis (PD). In patients aged <16 years the prevalence of ERF was 56.7 pmarp and the incidence 9.0 pmarp. A third of the prevalent patients had one or more reported comorbidities. At transfer to adult services, 81.5% of patients had a functioning renal transplant. Preemptive transplantation was seen to occur in a third of children starting RRT under 16 years, with lower rates seen in girls and ethnic minorities. Over the past 15 years for those referred early, there has been a rise in pre-emptive transplantation rates, rising from 26.2% in 1998-2002 to 36.3% in 2008-2012. Over the same period there has also been an increase in living donation from 7.1% to 18%. Survival in childhood amongst children starting RRT was the lowest in those aged less than two years., Conclusions: The findings of this report are similar to last year with continued improvement in data quality and electronic submission of data returns. The data provided in this report show slowly increasing trends of incidence and prevalence in children with established renal failure., (© 2014 S. Karger AG, Basel.)

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare autosomal recessive multisystem disorder caused by mutations in vacuolar protein sorting 33 homologue B (VPS33B) and VPS33B interacting protein, apical-basolateral polarity regulator (VIPAR). Cardinal features of ARC include congenital joint contractures, renal tubular dysfunction, cholestasis, severe failure to thrive, ichthyosis, and a defect in platelet alpha-granule biogenesis. Most patients with ARC do not survive past the first year of life. We report two patients presenting with a mild ARC phenotype, now 5.5 and 3.5 years old. Both patients were compound heterozygotes with the novel VPS33B donor splice-site mutation c.1225+5G>C in common. Immunoblotting and complementary DNA analysis suggest expression of a shorter VPS33B transcript, and cell-based assays show that c.1225+5G>C VPS33B mutant retains some ability to interact with VIPAR (and thus partial wild-type function). This study provides the first evidence of genotype-phenotype correlation in ARC and suggests that VPS33B c.1225+5G>C mutation predicts a mild ARC phenotype. We have established an interactive online database for ARC (https://grenada.lumc.nl/LOVD2/ARC) comprising all known variants in VPS33B and VIPAR. Also included in the database are 15 novel pathogenic variants in VPS33B and five in VIPAR., (© 2012 Wiley Periodicals, Inc.)

We describe the case of a patient with steroid sensitive nephrotic syndrome who is admitted with headaches, eye pain and reduced visual acuity. Despite thorough investigation no cause for the pain is identified. On a subsequent admission for recurrence of her symptoms her intraocular pressures are measured, which are markedly raised. Immediate medical treatment, as well as prompt weaning of her steroid therapy avoided the need for trabeculectomy surgery. We review this case and the literature surrounding this condition in children.

Aims: To describe the demographics of the paediatric RRT population under the age of 16 years in the UK and to analyse changes in demography with time., Methods: Data were collected from all 13 paediatric renal centres within the UK. A series of cross-sectional and longitudinal analyses were performed to describe the demographics of prevalent paediatric RRT patients., Results: A total of 870 children and young people under 18 with ERF were receiving treatment at paediatric nephrology centres in 2010. At the census date, 76.7% had a functioning transplant, 14.3% were receiving peritoneal dialysis (PD) and 9.0% were receiving haemodialysis (HD). In patients aged <16 years the prevalence of ERF was 59.3 pmarp and the incidence 8.1 pmarp. Analysis of trends over the last 15 years shows that both incidence and prevalence are increasing with the most marked increases in children aged 12-16 years and in ethnic minority groups. A third of the patients have one or more reported comorbidities. At transfer to adult services, 84.9% of patients had a functioning renal transplant., Conclusions: The data provided in this report show increasing trends over 15 years in the incidence and prevalence of established renal failure. This is important for the planning of the provision of care for children needing renal replacement therapy. The inclusion this year of an analysis of the patients transferring to adult services may assist in developing care pathways for this vulnerable group., (Copyright © 2012 S. Karger AG, Basel.)

Background: The British Association for Paediatric Nephrology Registry was established to analyse data related to renal replacement therapy (RRT) for children. The registry receives data from the 13 paediatric nephrology centres in the UK., Aim: To provide centre specific data so that individual centres can reflect on the contribution that their data makes to the national picture and to determine the extent to which their patient parameters meet nationally agreed audit standards for the management of children with established renal failure., Method: Data returns have been a mixture of electronic and paper returns. Data were analysed to calculate summary statistics and where applicable the percentage achieving an audit standard. The standards used were those set out by the Renal Association and the National Institute for Health and Clinical Excellence., Results: Anthropometric data confirmed that children receiving RRT are short compared to healthy peers. Amongst patients with a height z-score of <2SD between 2000 and 2010, 27% were receiving growth hormone if they were on dialysis compared to 10% if they had a functioning transplant. Blood pressure was higher in children receiving RRT than in healthy children with wide inter-centre variation. The percentage of patients achieving the treatment standards for haemoglobin and ferritin has gradually increased over the last decade, more noticeably in dialysis patients. Analysis by age showed that the proportion of children with a haemoglobin below the standard was greatest for the under 5 years age group irrespective of RRT modality. The control of renal bone disease remained challenging., Conclusions: Optimizing growth in children on RRT remains challenging and the control of bone biochemistry in children on dialysis is imperfect. However there is some room for optimism as this year's data shows an improving trend in the control of anaemia and systolic blood pressure., (Copyright © 2012 S. Karger AG, Basel.)

Tacrolimus is a widely used macrolide immunosuppressant that has a narrow therapeutic index and potential side effects including neurotoxicity. A 20-month-old boy with kidney disease secondary to prune belly syndrome variant, managed on peritoneal dialysis, received a deceased donor transplant. Standard immunosuppression was used. There was good early graft function. Post-transplant he developed fungal peritonitis associated with a significant reduction in graft function and was treated with caspofungin and fluconazole. Despite tacrolimus dose reduction he developed a rapid rise in tacrolimus concentration to a maximum of 72 ng/ml with an otherwise unexplained reduction in consciousness. He underwent a single volume exchange transfusion with packed red cells and 4.5% albumin (ratio 2:1). This resulted in immediate reduction of his tacrolimus concentration from 61.8 ng/ml to 35.2 ng/ml. The neurological deficit rapidly resolved. The fungal peritonitis was eradicated. Renal function recovered from a nadir of eGFR <10 ml/min/1.73 m² to a baseline of 30 ml/min/1.73 m². At 30 months post-transplant the child has creatinine of 1.4 mg/dl (eGFR of 31 ml/min/1.73 m²), and is developmentally appropriate with no neurological deficit. Red cell exchange transfusion is a potentially safe and effective way of managing severe and symptomatic tacrolimus toxicity.

Atypical haemolytic uraemic syndrome (aHUS) is frequently associated with mutations in the gene encoding complement factor H (CFH). The clinical response to plasma therapy in aHUS is variable. We present here our experience of plasma therapy in three aHUS patients with CFH mutations. Three children presented aged 4, 22 and 6 months (patients 1-3 respectively) in acute kidney injury requiring dialysis. Plasma therapy consisting of plasma filtration (patient 1) or plasma exchange (PEX; patients 2 and 3) was commenced early following presentation. This resulted in aHUS remission and cessation of dialysis after 2 weeks, 9 days and 2 weeks respectively. Relapses were common and associated with increasing the interval between PEX, but all responded to intensification of PEX therapy. Patient 1 recovered 50% of renal function after first presentation. She had four relapses and started peritoneal dialysis 41 months after presentation. Mutation screening of CFH showed a missense mutation (c.3546 G > T, p.Arg1182Ser) in exon 23. PEX in patient 2 was slowly tapered over 4 months to fortnightly sessions, but she relapsed when PEX was extended to every 4 weeks. Renal function remained normal 12 months post-presentation. Mutation screening of CFH showed a mutation in exon 23 (c.3590 T > C, p.Val1197Ala) and two additional sequence variants in exons 3 and 4. Patient 3 had two relapses associated with intercurrent illnesses concurrent with reducing PEX to weekly doses. Renal function was normal 5 months post-presentation. All three patients showed a good response to PEX with improved renal function both initially and following a relapse. Further research is necessary to determine the best maintenance strategy to delay or prevent end-stage kidney disease.

Background: The British Association for Paediatric Nephrology Registry was established fifteen years ago to analyse data related to renal replacement therapy for children. The registry receives data from the 13 paediatric nephrology centres in the UK. In 2008 the registry was relocated to the UK Renal Registry (UKRR)., Aim: To provide centre specific data so that individual centres can reflect on the contribution that their data makes to the national picture and to determine the extent to which their patient parameters meet nationally agreed audit standards for the management of children with established renal failure., Method: Data were submitted by either paper or electronic returns. Data were analysed to calculate summary statistics and where applicable the percentage achieving an audit standard. The standards used were those set out by the Renal Association and the National Institute for Health and Clinical Excellence., Results: Data were received from all but one centre. Anthropometric data confirmed that children with established renal failure (ERF) in the UK are short compared with their peers with no change in recent trends. In the UK as a whole, the control of blood pressure, anaemia and bone biochemistry is suboptimal., Conclusions: Key features of this report are the provision of centre specific data and comparison of data to audit standards. It is hoped that this information will provide a basis for discussion and a stimulus to improve the care of children with ERF., (Copyright © 2011 S. Karger AG, Basel.)

Aims: To describe the demographics of the paediatric RRT population under the age of 16 years in the UK and to analyse changes in demography with time., Methods: Extraction and analysis of data from the UK Renal Registry (UKRR)., Results: There were 751 children <16 years old with established renal failure (ERF) in the UK in December 2009. The reported prevalence under the age of 16 years was 65 per million age related population (pmarp) and the reported incidence 9.3 pmarp. The incidence and prevalence for South Asian patients was much higher than that of the White and Black populations. Of the patients for whom a primary renal diagnosis had been reported, renal dysplasia ± reflux was the most common cause of ERF accounting for 34.0% of prevalent cases. There has been growth in treatment numbers in all paediatric renal centres between 1995 and 2010. Whilst the rate of transplantation within 90 days of commencing RRT has remained at around 25-30% of patients, the use of HD has increased by 4% at the expense of PD., Conclusions: The paediatric ERF population continued to expand with a slow increase in both incidence and prevalence rates. The high incidence in patients from ethnic minority groups will lead to a greater proportion of the population being from these groups in time. To maintain the high proportion of engrafted patients it will be necessary to encourage living donation in the ethnic minority population., (Copyright © 2011 S. Karger AG, Basel.)

Aims: To describe the demographics of the paediatric RRT population in the UK and analyse changes in demographics with time., Methods: Extraction and analysis of data from the UK Paediatric Renal Registry and the UK Renal Registry (UKRR)., Results: The UK paediatric established renal failure (ERF) population in December 2008 was 905 patients. The prevalence under the age of 16 years was 56 per million age related population (pmarp) and the incidence 7.4 pmarp. The incidence and prevalence for South Asian patients was much higher than that of the White and Black populations. Renal dysplasia was the most common cause of ERF accounting for 33% of prevalent cases. Diseases with autosomal recessive inheritance were a common cause of ERF in all ethnic groups, 23.5% of prevalent and 18% of incident cases. Whilst the incidence and prevalence of diseases with autosomal recessive inheritance in the South Asian population was 3 times that of the white population, this was not the sole reason for the increased proportion of South Asian patients with ERF, as diseases with no defined inheritance were twice as common in this ethnic group than in White patients. Prevalent mortality stood at 9.4%. Most deaths were in patients presenting with ERF early in life and mortality varied markedly according to the aetiology of ERF. The proportion with new grafts from living donors has steadily risen to 54%. Children from ethnic minority groups were less likely to have an allograft and living donation was less frequent in this population. For those on dialysis, 56% were receiving peritoneal dialysis. This was the main treatment modality for patients under 4 years of age., Conclusions: The paediatric ERF population continued to expand slowly. Incidence and prevalence rates were stable and similar to other developed nations. The high incidence in patients from ethnic minority groups will lead to a greater proportion of the population being from these groups in time. To maintain the high proportion of engrafted patients it will be necessary to encourage living donation in the ethnic minority population. Case note analysis of the factors involved in mortality would be valuable., ((c) 2010 S. Karger AG, Basel.)

The effects of the calcimimetic drug Cinacalcet were assessed in six children with uncontrolled hyperparathyroidism secondary to stage 5 chronic kidney disease (CKD). Data were collected retrospectively regarding bone biochemistry and medications. Patients were between the ages of 11 months and 14 years on commencing Cinacalcet at initial doses of 0.4-1.4 mg/kg. Treatment, which was well tolerated in the majority and still on going in five patients, was for periods ranging between 3 months and 3 years. All six cases saw at least an 86% reduction in serum parathyroid hormone (PTH). Hypophosphataemia and/or hypocalcaemia were observed in three cases. Overall, achievement of UK Renal Association targets for corrected calcium (Ca), phosphate (P) and the calcium x phosphate product (Ca x P) were unaffected. We conclude that Cinacalcet is an effective treatment for correcting and sustaining correction of uncontrollable PTH levels seen in a difficult group of patients. Importantly, it has allowed the avoidance of parathyroidectomy for a significant time period in all cases. There remain questions about the effect of Cinacalcet on linear growth amongst paediatric dialysis patients, and future studies should aim to address this.

Background: The British Association for Paediatric Nephrology Registry was established thirteen years ago to analyse data related to renal replacement therapy for children. The registry receives data from the 13 paediatric nephrology centres in the UK. In 2008 the registry was relocated to the UK Renal Registry (UKRR)., Aim: To provide centre specific data so that individual centres can reflect on the contribution that their data makes to the national picture and to determine the extent to which their patient parameters meet nationally agreed audit standards for the management of children with established renal failure., Method: Data were submitted to the UKRR for analysis electronically via renal IT systems from 5 centres and on paper-based returns from the remaining centres. Data were analysed to calculate summary statistics and where applicable the percentage achieving an audit standard. The standards used were those set out by the Renal Association and the National Institute for Health and Clinical Excellence., Results: Data were received from all but one centre. Anthropometric data confirmed that children with ERF in the UK are short compared with their peers with no change in recent trends. In the UK as a whole, the control of blood pressure, anaemia and bone biochemistry is suboptimal, but for some parameters these appear to be better in the 2008 cohort than in the 1999-2008 cohort., Conclusions: Key features of this report are the provision of centre specific data and comparison of data to audit standards. It is hoped that this information will provide a basis for discussion and a stimulus to improve the care of children with ERF., ((c) 2010 S. Karger AG, Basel.)

Aims: To describe the demographics of the paediatric RRT population in the UK and analyse changes in demographics with time., Methods: Extraction and analysis of data from the UK paediatric Renal Registry., Results: The UK paediatric established renal failure (ERF) population in April 2008 was 875 patients. The prevalence under the age of 16 years was 55 per million age related population (pmp) and the incidence 7.92 pmp. The incidence and prevalence for South Asian and Other ethnic groups were 3 times that of the White and Black populations. Renal dysplasia was the most common cause of ERF accounting for 33% of prevalent cases. Diseases with autosomal recessive inheritance were more common in patients from ethnic minority groups. The spectrum of diseases seen has changed over a generation. Overall 5 year survival for children with ERF was 91.8%. Five year survival of infants starting dialysis was just 62%. Transplanted patients accounted for 74% of the current population. The proportion with grafts from living donors has steadily risen to 34%. Children from ethnic minority groups were less likely to have an allograft and living donation was less frequent in this population. For those on dialysis, 57% were receiving peritoneal dialysis. This was the main treatment modality for patients under 4 years of age., Conclusions: The paediatric ERF population continued to expand slowly. Incidence and prevalence rates were stable and similar to other developed nations. The high incidence in patients from ethnic minority groups will lead to a greater proportion of the population being from these groups in time. To maintain the high proportion of engrafted patients it will be necessary to encourage living donation in the ethnic minority population. The spectrum of diseases seen has already changed over a generation with the treatment of young children with diseases such as congenital nephrosis. The incidence of cystinosis causing ERF was reduced, probably reflecting better early treatment., (Copyright 2009 S. Karger AG, Basel.)

Atypical hemolytic uremic syndrome (aHUS) is a disorder characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Mutations, polymorphisms, and copy number variation in complement factors and inhibitors are associated with aHUS. In this study, we report the first functional non-synonymous polymorphism in the complement inhibitor C4b-binding protein (C4BP) alpha-chain (c.719G>A; p.Arg240His), which is associated with aHUS. This heterozygous change was found in 6/166 aHUS patients compared with 5/542 normal (chi2 = 6.021; p = 0.014), which was replicated in a second cohort of aHUS patients in which we found 5/170 carriers. The polymorphism does not decrease expression efficiency of C4BP. p.Arg240His is equally efficient as the wild type in binding and supporting degradation of C4BP but its ability to bind C3b and act as cofactor to its degradation both in fluid phase and on surfaces is impaired. This observation supports the hypothesis that dysregulation of the alternative pathway of complement is pivotal for aHUS. Three of the patients carry also mutations in membrane cofactor protein and factor H strengthening the hypothesis that individuals may carry multiple susceptibility factors with an additive effect on the risk of developing aHUS.