Jelena Stojanovic

UK Renal Registry 18th Annual Report: Chapter 10 Clinical, Haematological and Biochemical Parameters in Patients Receiving Renal Replacement Therapy in Paediatric Centres in the UK in 2014: 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.

UK Renal Registry 17th Annual Report

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.

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 17th Annual Report: Appendix B Definitions and Analysis Criteria

The take-on population is defined as all patients over 18 who started renal replacement therapy (RRT) at UK renal centres and did not have a recovery lasting more than 90 days within 90 days of starting RRT. The treatment timeline is used to define take-on patients as follows. If a patient has timeline entries from more than one centre then these are all combined and sorted by date. Then, the first treatment entry gives the first date of when they received RRT. This is defined as a ‘start date’. However, in the following situations there is evidence that the patient was already receiving RRT before this ‘start date’ and these people are not classed as takeon patients:

UK Renal Registry 15th Annual Report: Appendix A The UK Renal Registry Statement of Purpose

1. Executive summary 2. Introduction 3. Statement of intent 4. Relationships of the UK Renal Registry 5. The role of the UK Renal Registry for patients 6. The role of the UK Renal Registry for nephrologists 7. The role of the UK Renal Registry for Trust managers 8. The role of the UK Renal Registry for commissioning agencies 9. The role of the UK Renal Registry in national quality assurance schemes 10. References and websites

Large Volume Intraoperative Fluid Use in Small

Introduction With advances in surgical and medical transplantation, progressively younger children are being transplanted. There is no consensus and little evidence on the optimal intraoperative fluid volume/type and inotropic support in small recipients (<20kg). This study provides insight into the differences in intraoperative fluid and inotropic support use between small and large recipients (20>kg). Methods Patients transplanted between 2014 and 2017 were identifed from a local transplant database at the UKs largest pediatric transplant centre. We compared the volume of fluid required (mean percentage of dry weight), type of fluid used and inotropes required intraoperatively between the groups. Students T-test and FIshers test were used for analysis. Further analysis on <20kg group assessed the impact of intraoperative management on post-operative outcomes such as lenght of PICU admission and dependence on inotropic support post-operatively. Results Twenty-five small recipients (mean weight 14.9kg, SD 2.7kg) were compared with twenty-five large recipients (mean weight 48.6kg, SD 21.9). Small recipients received significantly higher volumes of fluid than large recipients (mean 15.4% (SD 7.5%) vs 6.8% (SD 2.4%), p<0.001) and received significantly more colloids intra-operatively (70% vs 25%, p-0.003). Mean fluid requirement for small recipients was 154ml/kg (range 63.7-333.3ml/kg) compared with 67.5ml/kg (range 32.6-114.3ml/kg) for large recipients. 96% of small recipients required intraoperative inotropes compared to 83% large recipients (not statistically significant, p=0.142). Mean stay at pediatric intesive care unit for small recipients was 66.3hours (SD 110.2) with mean dependence on inotropic support being 24.5 hours (SD 19.6 hours). Death-censored graft survival was 100% at 1 year (1 patient died from sepsis eight months post transplant). Conclusion This data suggest that small recipients require larger volumes of intraoperative fluid and more colloids than large recipients. It also confirms that large fluid volume and colloids are well tolerated by this group with excellent post-operative outcomes.

Improved Diagnosis and Management of Paediatric Renal Transplant Recipients Using the Banff 2013 Histopathological Classification

Introduction Since the publication of the 2013 Banff classification, adult studies have shown evidence of improved prognosis using the new histopathological criteria. Our study assesses for the first time the impact of the new classification on the diagnosis of acute antibody-mediated rejection (AMR) in paediatric renal transplant recipients (pRTR). Methods This single-centre study is a retrospective evaluation of 56 paediatric post-transplant de novo DSA-positive patients who had a percutaneous renal transplant biopsy due to renal allograft dysfunction from January 2006 to March 2012. Their biopsies were re-scored by a solitary specialist trained in 2013 Banff classification. The results were compared with previous classification as per 2003/2007 Banff criteria with results presented as range (median). Results At the time of biopsy, pRTR were aged 1.6 - 17.5 (median 14.9) years old with 412 - 2735 mean fluorescence intensity (MFI; maximal at 713 - 31,625; median 3466 and 4809). Following the 2013 Banff classification, there was a total of 5 cases of acute AMR compared to one confirmed and one suspicious AMR with the 2003/2007 Banff classification (with no change in the remaining 51 patients’ classification). Consequently, 5.3% (3 of 56) patients would have been diagnosed with T-cell mediated rejection with suboptimal treatment. There was an overall 70% (48 - 112%) decrease in the renal allograft function in the 6 months follow-up period after aggressive treatment for acute AMR and 2 of 3 patients had further rejection episodes in the following year. Conclusion This research supports the new Banff 2013 classification as a more precise classification in pRTR in the diagnosis of AMR with 5% of patients being correctly diagnosed and managed with improvement in renal allograft function.

Insights in Transplanting Complex Paediatric Renal Recipients With Vascular Anomalies

Background Children with end-stage kidney disease may have coexisting iatrogenic or congenital vascular anomalies making transplantation difficult. We describe our approach in 5 recipients with vascular anomalies and significant comorbidities, including one case of blood group incompatibility. Methods Five children aged 3 to 17 years (median, 7 years), weighing 14 to 34 kg (median, 18 kg) kg of whom 4 had occluded inferior vena cava or iliac veins and 2 had previous complex vascular reconstructions before transplantation for midaortic syndrome and multiple aortic aneurysms, respectively underwent renal transplantation. To establish implant feasibility surgery was commenced in 2 recipients before the donor surgery. Results There was 4 (80%) of 5 patient survival after 1 death from sepsis (with a functioning graft) and 2 cases of delayed graft function. At the latest median follow-up of 19 months, there was 100% (death-censored) renal allograft survival with estimated glomerular filtration rates (mL/min per 1.73 m2) of 43 to 72 (median, 55). Conclusions We conclude that major vascular anomalies do not necessarily preclude transplantation in complex pediatric patients and that surgical exploration of the recipient before commencing the donor surgery is valuable where feasibility and safety are uncertain. In addition, we have developed a novel classification system of congenital vascular abnormalities and propose its use in complex pediatric transplantation.

UK Renal Registry 15th Annual Report: Appendix D Methodology used for Analyses of PCT/HB Incidence and Prevalence Rates and of Standardised Ratios

The areas used were the 146 English primary care trusts (PCTs), the five English care trusts, the seven Welsh Local Health Boards, the fourteen Scottish Health Boards and the five Health and Social Care Trusts in Northern Ireland – these different types of area are collectively called PCT/HBs here. These areas in England are likely to undergo significant reorganisation in the next few years with the introduction of clinical commissioning groups. There will be more of these areas each containing smaller population groups, although the boundaries have yet to be finalised.

UK Renal Registry 15th Annual Report: Appendix E Methodology for Estimating Catchment Populations of Renal Centres in England for Dialysis Patients

Providing accurate centre-level incidence and prevalence rates for patients receiving renal replacement therapy (RRT) in the UK was limited until the 13th Annual Report by the difficulty in estimating the catchment population from which the RRT population is derived. One reason for this is that the geographical boundaries separating renal centres are relatively arbitrary and dependent upon a number of factors including referral practice, patient choice and patient movement. Previously incidence and prevalence rates had been calculated at Local Authority/Primary Care Trust/Health Board level where denominator data were available, but not at renal centre level. UK Renal Registry (UKRR) Annual Reports prior to the 13th suggested an estimate of the size of the catchment populations. These were extrapolated figures originally derived from data in the 1992 National Renal Survey undertaken by Paul Roderick. The purpose of this document is to present an estimate of the dialysis catchment population for all renal centres in England. The document also contains a methodological description and discussion of the limitations of this estimate. These catchment population estimates were used in the 13th Annual Report (chapter 1: UK RRT Incidence in 2009: national and centre-specific analyses) to calculate RRT incidence rates by renal centre, rather than only by Primary Care Trust/HB. From the 14th Annual Report both incidence and prevalence rates are given by renal centre as well as by Primary Care Trust/HB.