Haemolytic uraemic syndrome in children England, Wales, Northern Ireland, and Ireland: A prospective cohort study.

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.

Increasing trends in hemodialysis and living donor kidney transplantation for children and young people in the United Kingdom.

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.

Long-term outcomes and response to treatment in diacylglycerol kinase epsilon nephropathy.

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.

Psychosocial Health and Lifestyle Behaviors in Young Adults Receiving Renal Replacement Therapy Compared to the General Population: Findings From the SPEAK Study.

RATIONALE & OBJECTIVE: Patients in late adolescence and early adulthood receiving renal replacement therapy (RRT) face disruption to normal activities, which affects well-being. We aimed to define psychosocial and lifestyle outcomes for young adults on RRT compared to the general population. STUDY DESIGN: We undertook a cross-sectional survey (the SPEAK [Surveying Patients Experiencing Young Adult Kidney Failure] Study) using validated measures and general population comparator data from the Health Survey for England and Avon Longitudinal Study of Parents and Children. Additional clinical information was obtained from the UK Renal Registry. SETTING & PARTICIPANTS: 16- to 30-year-olds receiving RRT. OUTCOMES: Psychosocial health and lifestyle behaviors. ANALYTICAL APPROACH: We compared outcomes between populations using age- and sex-adjusted regression models, weighted to account for response bias by sex, ethnicity, and socioeconomic status. Our findings were used to update recent meta-analyses. RESULTS: We recruited 976 young adults and 64% responded to the survey: 417 (71%) with kidney transplants and 173 (29%) on dialysis therapy. Compared to the general population, young adults on RRT were less likely to be in a relationship and have children and more likely to live in the family home, receive no income, and be unable to work due to health. They had poorer quality of life, worse well-being, and twice the likelihood of a psychological disturbance (OR, 2.7; 95% CI, 2.0-3.7; P<0.001). They reported less smoking, alcohol and drug abuse, and crime. In a meta-analysis, our study showed the greatest differences in quality of life compared to the general population. LIMITATIONS: Cross-sectional study design, meaning that we could not track the impact of treatment changes on the outcomes. CONCLUSIONS: This study involving a large cohort of young adult transplant recipients and dialysis patients provides evidence of worse psychosocial outcomes but more positive lifestyle behaviors in young adults on RRT compared to the age-matched general population.

The clinical epidemiology of young adults starting renal replacement therapy in the UK: presentation, management and survival using 15 years of UK Renal Registry data.

Background: Clinical epidemiology data for young adults on renal replacement therapy (RRT) are lacking. While mostly transplanted, they have an increased risk of graft loss during young adulthood. Methods: We combined the UK Renal Registry paediatric and adult databases to describe patient characteristics, transplantation and survival for young adults. We grouped patients 11-30 years of age starting RRT from 1999 to 2008 by age band and examined their course during 5 years of follow-up. Results: The cohort (n = 3370) was 58% male, 79% white and 29% had glomerulonephritis. Half (52%) started RRT on haemodialysis (HD). Most (78%) were transplanted (18% pre-emptive, 61% as second modality); 11% were not listed for transplant. Transplant timing varied by age group. The deceased:living donor kidney transplant ratio was 2:1 for 11-<16 year olds and 1:1 otherwise. Median deceased donor transplant waiting times ranged from 6 months if <16 years of age to 17 months if ≥21 years. Overall 8% died, with being on dialysis and not transplant listed versus transplanted {hazard ratio [HR] 16.6 [95% confidence interval (CI) 10.8-25.4], P < 0.0001} and diabetes versus glomerulonephritis [HR 4.03 (95% CI 2.71-6.01), P < 0.0001] increasing mortality risk. Conclusions: This study highlights the frequent use of HD and the importance of transplant listing and diabetes for young adults. More than half the young adults in our cohort started renal replacement therapy on HD. One in 10 young adults were not listed for transplant by 5 years and were ∼20 times more likely to die than those who were transplanted. Diabetes as a primary renal disease was common among young adults and associated with increased mortality. Overall, almost 1 in 10 young adults had died by 5 years from the start of RRT.

Continually improving standards of care: The UK Renal Registry as a translational public health tool.

A disease registry uses observational study methods to collect defined data on patients with a particular condition for a predetermined purpose. By providing comprehensive standardised data on patients with kidney disease, renal registries aim to provide a 'real world' representation of practice patterns, treatment and patient outcomes that may not be captured accurately by other methods, including randomised controlled trials. Additionally, using registries to measure variations in outcomes and audit care against standards is crucial to understanding how to improve quality of care for patients in an efficacious and cost-effective manner. Registries also have the potential to be a powerful scientific tool that can monitor and support the translational process between research and routine clinical practice, although their limitations must be borne in mind. In this review, we describe the role of the UK Renal Registry as a tool to support translational research. We describe its involvement across each stage of the translational pathway: from hypothesis generation, study design and data collection, to reporting of long-term outcomes and quality improvement initiatives. Furthermore we explore how this role may bring about improvements in care for adults and children with kidney disease.

MAGI2 Mutations Cause Congenital Nephrotic Syndrome.

Steroid-resistant nephrotic syndrome (SRNS), a heterogeneous disorder of the renal glomerular filtration barrier, results in impairment of glomerular permselectivity. Inheritance of genetic SRNS may be autosomal dominant or recessive, with a subset of autosomal recessive SRNS presenting as congenital nephrotic syndrome (CNS). Mutations in 53 genes are associated with human SRNS, but these mutations explain ≤30% of patients with hereditary cases and only 20% of patients with sporadic cases. The proteins encoded by these genes are expressed in podocytes, and malfunction of these proteins leads to a universal end point of podocyte injury, glomerular filtration barrier disruption, and SRNS. Here, we identified novel disease-causing mutations in membrane-associated guanylate kinase, WW, and PDZ domain-containing 2 (MAGI2) through whole-exome sequencing of a deeply phenotyped cohort of patients with congenital, childhood-onset SRNS. Although MAGI2 has been shown to interact with nephrin and regulate podocyte cytoskeleton and slit diaphragm dynamics, MAGI2 mutations have not been described in human SRNS. We detected two unique frameshift mutations and one duplication in three patients (two families); two siblings shared the same homozygous frameshift mutation, whereas one individual with sporadic SRNS exhibited compound heterozygosity. Two mutations were predicted to introduce premature stop codons, and one was predicted to result in read through of the normal translational termination codon. Immunohistochemistry in kidney sections from these patients revealed that mutations resulted in lack of or diminished podocyte MAGI2 expression. Our data support the finding that mutations in the MAGI2 gene are causal for congenital SRNS.

Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland.

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.

The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to a ß cell phenotype.

BACKGROUND: Mutation specific effects in monogenic disorders are rare. We describe atypical Fanconi syndrome caused by a specific heterozygous mutation in HNF4A. Heterozygous HNF4A mutations cause a beta cell phenotype of neonatal hyperinsulinism with macrosomia and young onset diabetes. Autosomal dominant idiopathic Fanconi syndrome (a renal proximal tubulopathy) is described but no genetic cause has been defined. METHODS AND RESULTS: We report six patients heterozygous for the p.R76W HNF4A mutation who have Fanconi syndrome and nephrocalcinosis in addition to neonatal hyperinsulinism and macrosomia. All six displayed a novel phenotype of proximal tubulopathy, characterised by generalised aminoaciduria, low molecular weight proteinuria, glycosuria, hyperphosphaturia and hypouricaemia, and additional features not seen in Fanconi syndrome: nephrocalcinosis, renal impairment, hypercalciuria with relative hypocalcaemia, and hypermagnesaemia. This was mutation specific, with the renal phenotype not being seen in patients with other HNF4A mutations. In silico modelling shows the R76 residue is directly involved in DNA binding and the R76W mutation reduces DNA binding affinity. The target(s) selectively affected by altered DNA binding of R76W that results in Fanconi syndrome is not known. CONCLUSIONS: The HNF4A R76W mutation is an unusual example of a mutation specific phenotype, with autosomal dominant atypical Fanconi syndrome in addition to the established beta cell phenotype.

Initial steroid sensitivity in children with steroid-resistant nephrotic syndrome predicts post-transplant recurrence.

Of children with idiopathic nephrotic syndrome, 10%-20% fail to respond to steroids or develop secondary steroid resistance (termed initial steroid sensitivity) and the majority progress to transplantation. Although 30%-50% of these patients suffer disease recurrence after transplantation, with poor long-term outcome, no reliable indicator of recurrence has yet been identified. Notably, the incidence of recurrence after transplantation appears reduced in patients with steroid-resistant nephrotic syndrome (SRNS) due to monogenic disorders. We reviewed 150 transplanted patients with SRNS to identify biomarkers that consistently predict outcome of SRNS after transplantation. In all, 25 children had genetic or familial SRNS and did not experience post-transplant recurrence. We reviewed phenotypic factors, including initial steroid sensitivity, donor type, age, ethnicity, time to ESRD, and time on dialysis, in the remaining 125 children. Of these patients, 57 (45.6%) developed post-transplant recurrence; 26 of 28 (92.9%) patients with initial steroid sensitivity recurred after transplantation, whereas only 26 of 86 (30.2%) patients resistant from the outset recurred (odds ratio, 30; 95% confidence interval, 6.62 to 135.86; P<0.001). We were unable to determine recurrence in two patients (one with initial steroid sensitivity), and nine patients did not receive initial steroids. Our data show that initial steroid sensitivity is highly predictive of post-transplant disease recurrence in this pediatric patient population. Because a pathogenic circulating permeability factor in nephrotic syndrome remains to be confirmed, we propose initial steroid sensitivity as a surrogate marker for post-transplant recurrence.

Survival and clinical outcomes of children starting renal replacement therapy in the neonatal period.

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.

Longitudinal changes in body mass index following renal transplantation in UK children.

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.

Psychosocial Health Among Young Adults With Kidney Failure: A Longitudinal Follow-up of the SPEAK (Surveying Patients Experiencing Young Adult Kidney Failure) Study.

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.

The psychosocial impact of kidney failure in young adults is implicated in the observed higher risk of transplant loss and death. The Surveying Patients Experiencing Young Adult Kidney Failure (SPEAK) study investigated the psychosocial health of young adults (16-30 years) in the UK receiving kidney replacement therapy and found they had poorer outcomes than the age-matched general population. In this 5-year follow-up study, we observed that as this group matured, they lagged behind their peers in terms of both lifecourse and psychological outcomes. Dialysis recipients had poorer psychosocial health compared to transplant recipients. This emphasizes the lasting impact of kidney failure on young adults' psychosocial health, particularly for those receiving dialysis, highlighting the need for better mental health support and treatment.

UK Renal Registry 15th annual report: Chapter 4 demography of the UK paediatric renal replacement therapy population in 2011.

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.

UK Renal Registry 15th annual report: Chapter 7 clinical, haematological and biochemical parameters in patients receiving renal replacement therapy in paediatric centres in the UK in 2011: national and centre-specific analyses.

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.

UK Renal Registry 16th annual report: chapter 7 demography of the UK paediatric renal replacement therapy population in 2012.

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.

UK Renal Registry 16th annual report: chapter 13 clinical, haematological and biochemical parameters in patients receiving renal replacement therapy in paediatric centres in the uk in 2012: national and centre-specific analyses.

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.

Epidemiology of childhood acute kidney injury in England using e-alerts.

Background: Few studies describe the epidemiology of childhood acute kidney injury (AKI) nationally. Laboratories in England are required to issue electronic (e-)alerts for AKI based on serum creatinine changes. This study describes a national cohort of children who received an AKI alert and their clinical course. Methods: A cross-section of AKI episodes from 2017 are described. Hospital record linkage enabled description of AKI-associated hospitalizations including length of stay (LOS) and critical care requirement. Risk associations with critical care (hospitalized cohort) and 30-day mortality (total cohort) were examined using multivariable logistic regression. Results: In 2017, 7788 children (52% male, median age 4.4 years, interquartile range 0.9-11.5 years) experienced 8927 AKI episodes; 8% occurred during birth admissions. Of 5582 children with hospitalized AKI, 25% required critical care. In children experiencing an AKI episode unrelated to their birth admission, Asian ethnicity, young (<1 year) or old (16-<18 years) age (reference 1-<5 years), and high peak AKI stage had higher odds of critical care. LOS was higher with peak AKI stage, irrespective of critical care admission. Overall, 30-day mortality rate was 3% (n = 251); youngest and oldest age groups, hospital-acquired AKI, higher peak stage and critical care requirement had higher odds of death. For children experiencing AKI alerts during their birth admission, no association was seen between higher peak AKI stage and critical care admission. Conclusions: Risk associations for adverse AKI outcomes differed among children according to AKI type and whether hospitalization was related to birth. Understanding the factors driving AKI development and progression may help inform interventions to minimize morbidity.

Associations among genotype, clinical phenotype, and intracellular localization of trafficking proteins in ARC syndrome.

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.