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Methylmalonic acidemia (MMAemia) is characterized by accumulation of methylmalonic acid (MMA) in all body tissues. To minimize disease-related complications, isolated kidney (KTx), liver (LTx) or combined liver-kidney transplantation (LKTx) have been suggested. However, the impact of these different transplant strategies on outcome are unclear.In this multicenter retrospective observational study, we compared plasma MMA levels and estimated glomerular filtration rate (eGFR) data of 83 patients. Sixty-eight patients (82%) had a mutsup0/sup-type MMAemia, one patient had a mutsup-/sup-type MMAemia, and seven (7.3%) had an inherited defect in cobalamin metabolism (cblA- or cblB-type MMAemia). Median observation period was 3.7 years (0-15.1 years).Twenty-six (31%) patients underwent KTx, 24 (29%) LTx and 33 (40%) LKTx. Posttransplant, mean plasma MMA concentration significantly decreased in all three cohorts; but at month 12, plasma MMA in KTx (1372 ± 1101 μmol/L) was 7.8-fold higher than in LTx (176 ± 103 μmol/L; Plt; 0.001) and 6.4-fold higher than in LKTx (215 ± 110 μmol/L; Plt; 0.001). Comparable data were observed at month 24. At time of transplantation, mean eGFR in KTx was 18.1 ± 24.3 mL/min/1.73 msup2/sup, in LTx 99.8 ± 29.9 mL/min/1.73 msup2/sup, and in LKTx 31.5 ± 21.2 mL/min/1.73 msup2/sup. At month 12 posttransplant, mean eGFR in KTx (62.3 ± 30.3 mL/min/1.73 msup2/sup) was 33.4% lower than in LTx (93.5 ± 18.3 mL/min/1.73 msup2/sup; P = 0.0053) and 25.4% lower than in LKTx (83.5 ± 26.9 mL/min/1.73 msup2/sup; P = 0.0403).In patients with isolated MMAemia, LTx and LKTx lead to markedly lower plasma MMA levels during the first 2 years posttransplant than KTx and are associated with a better preservation of kidney function. LTx should therefore be part of the transplant strategy in MMAemia.

The emergence and attendant mortality of vaccine-induced immune thrombocytopenia and thrombosis (VITT) as a consequence of vaccination against severe acute respiratory syndrome coronavirus 2 have resulted in some patients with VITT being considered as deceased organ donors. Outcomes after kidney transplantation in this context are poorly described. Because the disease seems to be mediated by antiplatelet factor 4 antibodies, there is a theoretical risk of transmission via passenger leukocytes within the allograft.We analyzed the experience of kidney transplantation from donors with VITT in the United Kingdom between January and June 2021. We followed-up all recipients of kidney-only transplants from donors with VITT to detect major postoperative complications or features of disease transmission and assess graft survival and function.There were 16 kidney donors and 30 single kidney transplant recipients in our study period. Of 11 preimplantation biopsies, 4 showed widespread glomerular microthrombi. After a median of 5 mo, patient and graft survival were 97% and 90%, respectively. The median 3-mo estimated glomerular filtration rate was 51 mL/min/1.73 m 2 . Two recipients had detectable antiplatelet factor 4 antibodies but no evidence of clinical disease after transplantation. Major hemorrhagic complications occurred in 3 recipients, all of whom had independent risk factors for bleeding, resulting in the loss of 2 grafts. The involvement of VITT could not be completely excluded in one of these cases.The UK experience to date shows that favorable outcomes are possible after kidney transplantation from donors with VITT but highlights the need for ongoing vigilance for donor-related complications in these patients.

Renovascular hypertension in most cases requires endovascular treatment and/or surgery. This is technically much more difficult in small children and there is very limited published knowledge in this age group. We here present treatment and outcome of young children with renovascular hypertension at our institution. Children below 2 years of age, with renovascular hypertension between January 1998 and March 2020 were retrospectively reviewed. Demographics and treatment modalities were noted. Primary outcome was blood pressure within a week after the procedures and at last available visit. Sixty-six angiographies were performed in 34 patients. Median age at time of first angiography was 1.03 (interquartile range (IQR) 0.4–1.4) years and systolic blood pressure at presentation 130 (IQR 130–150) mm Hg. Thirty-eight percent (13/34) of children were incidentally diagnosed and 18% (6/34) presented with heart failure. Twenty-six (76%) children had main renal artery stenosis and 17 (50%) mid-aortic syndrome. Seventeen (50%) children showed intrarenal, six (18%) mesenteric, and three (9%) cerebrovascular involvement. Twenty patients underwent 45 percutaneous transluminal angioplasty procedures and seven children surgeries. In 44% of the 16 patients who underwent only percutaneous transluminal angioplasty blood pressure was normalized, 38% had improvement on same or decreased treatment and 19% showed no improvement. Complications were seen in 7.5% (5/66) of angiographies. In four of the seven (57%) children who underwent surgery blood pressure was normalized, two had improved (29%) and one unchanged (14%) blood pressure.Conclusion: In small children with renovascular hypertension below the age of 2 years, percutaneous transluminal angioplasty caused significant improvement in blood pressure with low complication profile. Surgery can be recommended where percutaneous transluminal angioplasty and medical treatments failed. What is Known:• Renovascular hypertension is diagnosed in all age groups from a few weeks of life until adulthood.• Both angioplasty and surgery are significantly more difficult to perform in small children and the published information on short and long-term outcome in these children is very scarce. What is New:• Children below the age of two years can safely and successfully undergo selective renal angiography and also safely be treated with angioplasty.• We here present a large group of babies and infants where angioplasty and in some cases surgery effectively and safely improved their blood pressure.

Background and objectives: C3 glomerulopathy and idiopathic Ig-associated membranoproliferative GN are kidney diseases characterized by abnormal glomerular complement C3 deposition. These conditions are heterogeneous in outcome, but approximately 50% of patients develop kidney failure within 10 years. Design, setting, participants, & measurements: To improve identification of patients with poor prognosis, we performed a detailed analysis of percutaneous kidney biopsies in a large cohort of patients. Using a validated histologic scoring system, we analyzed 156 native diagnostic kidney biopsies from a retrospective cohort of 123patients with C3 glomerulopathy and 33 patients with Ig-associated membranoproliferative GN. We used linear regression, survival analysis, and Cox proportional hazards models to assess the relationship between histologic and clinical parameters with outcome. Results: Frequent biopsy features were mesangial expansion and hypercellularity, glomerular basement membrane double contours, and endocapillary hypercellularity. Multivariable analysis showed negative associations between eGFR and crescents, interstitial inflammation, and interstitialfibrosis/tubular atrophy. Proteinuria positively associated with endocapillary hypercellularity and glomerular basement membrane double contours. Analysis of second native biopsies did not demonstrate associations between immunosuppression treatment and improvement in histology. Using a composite outcome, risk of progression to kidney failure associated with eGFR and proteinuria at the time of biopsy, cellular/fibrocellular crescents, segmental sclerosis, and interstitial fibrosis/tubular atrophy scores. Conclusions: Our detailed assessment of kidney biopsy data indicated that cellular/fibrocellular crescents and interstitial fibrosis/tubular atrophy scores were significant determinants of deterioration in kidney function.

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 ( 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.

There has not been a comprehensive global survey of pediatric-deceased donor allocation practices across all organs since the advent of deceased donor transplantation at the end of the 20th century. As an international community that is responsible for transplanting children, we set out to survey the existing landscape of allocation. We aimed to summarize current practices and provide a snapshot overview of deceased donor allocation practices to children across the world.The International Registry in Organ Donation and Transplantation (IRODAT, www.irodat.org) was utilized to generate a list of all countries in the world, divided by continent, that performed transplantation. We reviewed the published literature, published allocation policy, individual website references and associated links to publicly available listed allocation policies. Following this, we utilized tools of communication, relationships, and international fellowship to confirm deceased donation pediatric centers and survey pediatric allocation practices for liver, kidney, heart, and lung across the world. We summarize pediatric allocation practices by organ when available using source documents, and personal communication when no source documents were available.The majority of countries had either formal or informal policies directed toward minimizing organ distribution disparity among pediatric patients.Children have long-term life to gain from organ donation yet continue to die while awaiting transplantation. We summarize global strategies that have been employed to provide meaningful and sustained benefit to children on the waitlist.

Organ shortage for transplantation is a global problem for both adult and pediatric recipients and this is particularly apparent in certain areas of the world and within specific communities. Cultural and religious beliefs can influence both a decision by a potential donor and/or their family to donate as well as a potential recipient's or their family's decision to accept the need for transplantation, agree to be listed and accept an organ. Globally, there are cultural and religious diversities that can present significant challenges for the transplant professional, particularly those whose practice is based in multicultural communities. In the pediatric population, in particular, barriers to organ transplantation related to culture and religion have not been well-described, with resulting implications for how they should or could be effectively addressed. Therefore, this review was undertaken to elucidate cultural and religious barriers to pediatric organ transplantation and, where feasible, to identify facilitators and strategies for overcoming these barriers.

BACKGROUND AND OBJECTIVES: Membranoproliferative GN and C3 glomerulopathy are rare and overlapping disorders associated with dysregulation of the alternative complement pathway. Specific etiologic data for pediatric membranoproliferative GN/C3 glomerulopathy are lacking, and outcome data are based on retrospective studies without etiologic data. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 80 prevalent pediatric patients with membranoproliferative GN/C3 glomerulopathy underwent detailed phenotyping and long-term follow-up within the National Registry of Rare Kidney Diseases (RaDaR). Risk factors for kidney survival were determined using a Cox proportional hazards model. Kidney and transplant graft survival was determined using the Kaplan–Meier method. RESULTS: Central histology review determined 39 patients with C3 glomerulopathy, 31 with immune-complex membranoproliferative GN, and ten with immune-complex GN. Patients were aged 2–15 (median, 9; interquartile range, 7–11) years. Median complement C3 and C4 levels were 0.31 g/L and 0.14 g/L, respectively; acquired (anticomplement autoantibodies) or genetic alternative pathway abnormalities were detected in 46% and 9% of patients, respectively, across all groups, including those with immune-complex GN. Median follow-up was 5.18 (interquartile range, 2.13–8.08) years. Eleven patients (14%) progressed to kidney failure, with nine transplants performed in eight patients, two of which failed due to recurrent disease. Presence of >50% crescents on the initial biopsy specimen was the sole variable associated with kidney failure in multivariable analysis (hazard ratio, 6.2; 95% confidence interval, 1.05 to 36.6; P50% crescents on the initial biopsy specimen. CONCLUSIONS: Crescentic disease was a key risk factor associated with kidney failure in a national cohort of pediatric patients with membranoproliferative GN/C3 glomerulopathy and immune-complex GN. Presenting eGFR and crescentic disease help define prognostic groups in pediatric C3 glomerulopathy. Acquired abnormalities of the alternative pathway were commonly identified but not a risk factor for kidney failure.

Vesico-ureteric reflux (VUR) into transplanted kidneys in children and young people is a common occurrence, found in 19 to 60% of those who had an anti-reflux procedure and up to 79% in the absence of such a procedure. While VUR is unlikely to be of concern without evidence of symptomatic urinary tract infections, less certainty exists regarding outcomes when the VUR is associated with urinary tract infection (UTI) and transplant pyelonephritis. Issues explored will include additional risk factors that might predispose to UTI, any effect of pyelonephritis on acute and long-term kidney allograft function and practical strategies that may reduce the prevalence of infection.

Summary Chronic active Epstein–Barr virus (CAEBV) disease is a rare condition characterised by persistent EBV infection in previously healthy individuals. Defective EBV genomes were found in East Asian patients with CAEBV. In the present study, we sequenced 14 blood EBV samples from three UK patients with CAEBV, comparing the results with saliva CAEBV samples and other conditions. We observed EBV deletions in blood, some of which may disrupt viral replication, but not saliva in CAEBV. Deletions were lost overtime after successful treatment. These findings are compatible with CAEBV being associated with the evolution and persistence of EBV+ haematological clones that are lost on successful treatment.

Background A 3-year-old girl with clinical features of atypical HUS (complement Factor I mutation inherited from an asymptomatic mother and Factor H autoantibodies) was treated with plasma exchange, progressed to kidney failure (KF) aged 4 years, and received an en bloc kidney DCD transplant aged 8 years with primary graft non-function necessitating transplant nephrectomy at the time of transplantation. She subsequently underwent re-transplantation from her father. This is a retrospective study of electronic patient records and medical notes. Case-diagnosis/treatment A 9-year-old girl received an ABO-incompatible (ABOi) living-related kidney transplant from her father with recipient and donor blood groups of O and A, respectively, with baseline recipient anti-A titers 1:128 reducing to 1:4 at the time of transplant with B lymphocyte depletion with rituximab and four sessions of immunoadsorption. Six hours post-transplant, she had recurrence of aHUS and received the first dose of eculizumab. She continues on monthly home eculizumab infusions with stable kidney allograft function and negative anti-A titers 7 years post-kidney transplantation. Conclusions This is the first report of a pediatric high-risk ABOi living-related kidney transplantation in whom early relapse of aHUS was successfully treated with eculizumab with good long-term patient and allograft outcome.

Summary The increasing global prevalence of SARS‐CoV‐2 and the resulting COVID‐19 disease pandemic pose significant concerns for clinical management of solid organ transplant recipients (SOTR). Wearable devices that can measure physiologic changes in biometrics including heart rate, heart rate variability, body temperature, respiratory, activity (such as steps taken per day) and sleep patterns, and blood oxygen saturation show utility for the early detection of infection before clinical presentation of symptoms. Recent algorithms developed using preliminary wearable datasets show that SARS‐CoV‐2 is detectable before clinical symptoms in >80% of adults. Early detection of SARS‐CoV‐2, influenza, and other pathogens in SOTR, and their household members, could facilitate early interventions such as self‐isolation and early clinical management of relevant infection(s). Ongoing studies testing the utility of wearable devices such as smartwatches for early detection of SARS‐CoV‐2 and other infections in the general population are reviewed here, along with the practical challenges to implementing these processes at scale in pediatric and adult SOTR, and their household members. The resources and logistics, including transplant‐specific analyses pipelines to account for confounders such as polypharmacy and comorbidities, required in studies of pediatric and adult SOTR for the robust early detection of SARS‐CoV‐2, and other infections are also reviewed.

Background The aim of this study was to investigate whether being on dialysis at the time of renal transplantation affected renal allograft survival in paediatric renal transplant recipients (pRTRs). Methods Retrospective study of UK Transplant Registry (National Health Service Blood and Transplant) data on all children (aged, The debate about the benefit of pre-emptive kidney transplantation in paediatric patients gets support by recent data from the UK Transplant Registry. Five years graft survival rate was significantly better in pre-emptive transplantation, and dialysis's time negatively impacted.

CRADLE was a 36-month multicenter study in pediatric (≥1 to

Professionals working in pediatric transplantation commonly encounter complex ethical dilemmas. Most ethical research in transplantation is related to adult practice. We aimed to gain insight into ethical issues faced by transplant professionals when dealing with pediatric transplant recipients.A two-stage study was designed; the first part was a questionnaire completed by 190 (80%) members of the International Pediatric Transplant Association (IPTA) from over 30 different countries. This was followed by a multidisciplinary focus group that explored the preliminary data of the survey.A total of 38% (56 of 149) respondents of the questionnaire had experienced an ethical issue between 2016 and 2018. Surgeons were more likely to have encountered an ethical issue as compared with physicians (60% vs. 35.7%, p = .035). Clinicians from Europe were more likely to have experienced an ethical issue in living organ donation compared with those from North America (78.9% vs. 52.5%, p = .005), with common ethical concerns being psychosocial evaluation and follow-up care of donors. The focus group highlighted the importance of a multidisciplinary approach to ethical issues.The results of this study can direct future research into pediatric transplantation ethics with the aim of producing educational resources, policies, and ethical guidelines.

Main Problem: Preemptive kidney transplantation (PKT) is performed prior to dialysis initiation to avoid dialysis-related morbidity and mortality in children and adolescents. We undertook a systematic review to compare clinical outcomes in PKT versus kidney transplantation after dialysis initiation in paediatric patients.Methods: The bibliographic search identified studies that compared paediatric recipients of a first or subsequent, living or deceased donor PKT versus non-preemptive kidney transplant. Methodological quality was assessed for all studies. Data were pooled using the random-effects model.Results: Twenty-two studies (n = 22,622) were included. PKT reduced the risk of overall graft loss (relative risk (RR) .57, 95% CI: .49–.66) and acute rejection (RR: .81, 95% CI: .75–.88) compared to transplantation after dialysis. Although no significant difference was observed in overall patient mortality, the risk of patient death was found to be significantly lower in PKT patients with living donor transplants (RR: .53, 95% CI: .34–.83). No significant difference was observed in the incidence of delayed graft function.Conclusion: Evidence from observational studies suggests that PKT is associated with a reduction in the risk of acute rejection and graft loss. Efforts should be made to promote and improve rates of PKT in this group of patients (PROSPERO).Systematic Review Registration:https://clinicaltrials.gov/, CRD42014010565

The risk of tuberculosis (TB) disease is increased in children with chronic kidney disease (CKD), even higher in stage 5 CKD/kidney failure and especially high after kidney transplantation due to immunosuppression. TB disease may follow recent primary infection, or result from reactivation of latent infection. Reactivation is more common in adults, while progression following primary infection makes up a greater proportion of disease in children. Recommendations for preventing TB disease in some low TB incidence countries have previously included offering Bacillus Calmette-Guérin (BCG) vaccine to all children listed for kidney transplant if they had not received this as part of previous national immunisation programmes. Based on the available evidence, we recommend modifying this practice, focusing instead on awareness of risk factors for TB exposure, infection and disease and the use of appropriate testing strategies to identify and treat TB infection and disease. Supplementary Information The online version contains supplementary material available at 10.1007/s00467-020-04844-5.

Background The use of cell-free DNA (cfDNA) as a noninvasive biomarker to detect allograft damage is expanding rapidly. However, quantifying the low fraction of donor-derived cfDNA (ddcfDNA) is challenging and requires a highly sensitive technique. ddcfDNA detection through unique donor single nucleotide polymorphisms (SNPs) is a recent new approach, however there are limited data in pediatric solid organ transplant (SOT) recipients. Methods We developed an assay using a combination of 61 SNPs to quantify the ddcfDNA accurately using a custom R script to model for both the patient and donor genotypes requiring only a single sample from the allograft recipient. Performance of the assay was validated using genomic DNA (gDNA), cfDNA and donor samples where available. Results The R “genotype-free” method gave results comparable to when using the known donor genotype. applicable to both related and unrelated pairs and can reliably measure ddcfDNA (limit of blank, below 0.12%; limit of detection, above 0.25%; limit of quantification 0.5% resulting in 84% accuracy). 159 pediatric SOT recipients (kidney, heart, and lung) were tested without the need for donor genotyping. Serial sampling was obtained from 82 patients. Conclusion We have developed and validated a new assay to measure the fraction of ddcfDNA in the plasma of pediatric SOT recipients. Our method can be applicable in any donor-recipient pair without the need for donor genotyping and can provide results in 48 h at a low cost. Additional prospective studies are required to demonstrate its clinical validity in a large cohort of pediatric SOT recipients.

One of the main objectives of the European health policy framework is to ensure equitable access to high-quality health services across Europe. Here we examined country-specific kidney transplantation and graft failure rates in children and explore their country- and patient-level determinants. Patients under 20 years of age initiating kidney replacement therapy from January 2007 through December 2015 in 37 European countries participating in the ESPN/ERA-EDTA Registry were included in the analyses. Countries were categorized as low-, middle-, and high-income based on gross domestic product. At five-years of follow-up, 4326 of 6909 children on kidney replacement therapy received their first kidney transplant. Overall median time from kidney replacement therapy start to first kidney transplantation was 1.4 (inter quartile range 0.3-4.3) years. The five-year kidney transplantation probability was 48.8% (95% confidence interval: 45.9-51.7%) in low-income, 76.3% (72.8-79.5%) in middle-income and 92.3% (91.0-93.4%) in high-income countries and was strongly associated with macro-economic factors. Gross domestic product alone explained 66% of the international variation in transplantation rates. Compared with high-income countries, kidney transplantation was 76% less likely to be performed in low-income and 58% less likely in middle-income countries. Overall five-year graft survival in Europe was 88% and showed little variation across countries. Thus, despite large disparities transplantation access across Europe, graft failure rates were relatively similar. Hence, graft survival in low-risk transplant recipients from lower-income countries seems as good as graft survival among all (low, medium, and high risk) graft recipients from high-income countries.

Systemic lupus erythematosus is a rare lifelong multi-systemic autoimmune condition. Juvenile-onset SLE (JSLE) is recognized to have a more active disease course when compared with adult-onset disease and patients have a worse long-term survival. Kidney involvement occurs in over 50% of children and treatment decisions are guided by the histological classification. Several international groups have produced treatment protocols that rely on an intense period of immunosuppression to halt the acute kidney inflammatory process, followed by maintenance therapy with close observation for disease improvement and prompt evaluation of disease flares. A reduced glomerular filtration rate at presentation is predictive of later stage chronic kidney disease (CKD) in multivariate analysis. Kidney remission remains suboptimal with only 40–60% of patients achieving complete remission. Kidney flares are seen in over a third of patients. The rate of CKD 5 is reported to be up to 15% and the presence of lupus nephritis (LN) has an established link with an associated increase in mortality. In established kidney failure, transplantation seems to be the optimal kidney replacement modality for this group of patients, ideally after a period of disease quiescence. Modified outcome measures in clinical trials have demonstrated that biologic agents can be effective in this disease. Current biologic agents under investigation include obinutuzimab, belimumab, atacicept, anifrolumab, tocilizumab, eculizumab, dapirolizumab, and abatacept. Future research should focus on discovering early disease biomarkers, including surrogates for later cardiovascular disease, and evaluating biological agents as adjuncts to improve the rates of complete remission and subsequently influence the kidney outcome. The aim of this review article is to summarize the current kidney outcomes for this disease with a view to identifying key areas that may help to reduce the risk of long-term CKD.

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., Graphical abstract

Children with end-stage kidney disease (ESKD) requiring renal replacement therapy (RRT) are usually managed in one of the 13 paediatric nephrology centres in the United Kingdom. The UK Renal Registry (UKRR) collects, analyses and reports data on children receiving RRT in these centres.The UKRR annual report presents analyses relating to the attainment of the Renal Association audit measures [1], national averages to enable benchmarking and long-term trends for children on RRT for ESKD. Data are reported by centre to enable between centre comparisons.To improve the timeliness of data reporting, the format of the UKRR 21st Annual Report, which included data to December 31, 2017 [2], differs significantly to that of previous years. For paediatric data, changes include a single chapter reporting demographic and biochemical data, reduced clinical commentary, a higher threshold for data quality control (with data completeness at least 70%) and greater alignment of analyses to the Renal Association guidelines [1].In this article, we summarise the analyses of paediatric data presented in the UKRR 21st Annual Report. The corresponding adult summary is published separately in this issue. The full UKRR 21st Annual Report can be accessed at https://www.renalreg.org/reports/data_to_end_2017/.

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.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.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.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 lowest2 years. Moreover, there was a demographic shift from Caucasian toward Asian/other ethnicity and from CAKUT to other primary kidney diseases.

Now that covid-19 vaccination of children in the UK is starting, it is essential that the legal basis of consent is well understood

After the major changes with regard to acute and chronic ABMR in the Banff classification initiated in 2013, there has been an improvement in diagnosing antibody-mediated rejection (ABMR) in adult studies but no data have been published in the paediatric population. We assessed 56 paediatric kidney transplant biopsies due to kidney dysfunction in patients with donor-specific antibodies (DSA) in a retrospective single-centre study between January 2006 and March 2012. The results were compared with 2003/2007 Banff classification noting the subsequent 2017 and 2019 modifications do not change the 2013 Banff classification with regard to acute antibody-mediated rejection (apart from the addition of gene transcripts/classifiers that do not affect our analysis). Following the 2013 Banff classification, there were seven cases (12.5%) diagnosed with ABMR that would have been misclassified when applying the 2003/2007 classification. Evaluating the histological features of all ABMR-related cases, we report the importance of v− (intimal arteritis) and t− (tubulitis) lesions: absence of v− and t− lesions in the biopsy is related to significantly higher kidney allograft survival (OR 7.3, 95%CI 1.1–48.8, p = 0.03 and OR 5.3, 95%CI 1.2–25.5, p = 0.04 respectively). Moreover, absence of t− lesions was associated with significantly fewer rejection episodes the year after the initial biopsy (OR 5.1, 95%CI 1.4–19.8, p = 0.01). Our study supports that the updated 2013 Banff classification shows superior clinicopathological correlation in identifying ABMR in paediatric kidney transplant recipients. Our results can be extrapolated to the recently updated 2019 Banff classification.

Aims Rituximab is a chimeric IgG-1 monoclonal antibody that depletes B cells, aiding in the treatment of several conditions including autoimmune diseases. It is not licensed for use in children. This study aimed to quantify the B cell-related pharmacodynamics of rituximab in children with autoimmune disease. Methods Routine electronic health record data were collected at a large paediatric tertiary hospital in London, UK. Dosing protocols were either 2 × 750 mg/m2 intravenous infusions of rituximab on days 1 and 15, or 4 × 375 mg/m2 infusions on days 1, 8, 15 and 22. Rituximab pharmacokinetics (PK) were not measured but CD19+ lymphocyte counts were taken before and after rituximab treatment. A dose-response model was constructed describing the life cycle of CD19+ lymphocytes, with rituximab assumed to increase the death rate. Rituximab effect was assumed to decay by first-order kinetics. Results In total, 258 measurements of CD19+ lymphocyte counts were collected from 39 children with 8 autoimmune diseases. The elimination rate constant (% relative standard error) of rituximab effect decay was 0.036 (22.7%) days-1 and CD19+ turnover was 0.02 (41%) days-1 corresponding to half-lives of 19 and 35 days respectively. Rituximab increased CD19+ death rate 35-fold, with methotrexate and cyclophosphamide associated with further increases. Simulations suggested that a single infusion of 750 mg/m2 provides similar 6-month suppression of CD19+ lymphocytes to current dosing. Conclusions Rituximab pharmacodynamics (PD) in paediatric autoimmune diseases has been described. Compared with rituximab alone, the additional effect of methotrexate or cyclophosphamide was statistically significant but small.

This review reports the outcomes of paediatric renal transplantation in the United Kingdom over the last 25 years. UK Transplant Registry data on 3236 paediatric renal transplants performed between 1 January 1992 and 31 December 2016 were analysed. Significant improvements in human leucocyte antigen (HLA) matching have been achieved; 84% of recipients received 000 or favourable (0 DR and 0 or 1 B) mismatched kidneys in 2016 compared with 27% in 1992. The median waiting time has increased from 126 days in 1999 to 351 days in 2016. Tacrolimus replaced ciclosporin in most immunosuppressive regimens after 2002. Renal transplant outcome has improved significantly, mainly because of a reduction in early graft loss. One-year donation after brain death renal allograft survival for those transplanted from 2012 to 2016 was 98%, compared with 72% for those transplanted from 1987 to 1991. Renal allograft survival for first kidney only transplants at 1, 5, 10, 20 and 25 years were 89%, 79%, 65%, 42% and 33% respectively. Superior survival with living donor was maintained throughout the study period with 25-year graft survival at 33% compared with 31% from deceased donor (P < 0.0001). Changes in immunosuppression regimens, improvements in HLA matching and a reduction of cold ischaemia time may in part explain the improvements in graft survival.

In a 12-month, multicenter, open-label study, 106 children were randomized at 4 to 6 weeks after kidney transplantation to switch to everolimus with reduced TAC (EVR/rTAC) and steroid elimination from month 5 posttransplant or to continue standard tacrolimus with mycophenolate mofetil (sTAC/MMF) and steroids. The cumulative incidence of a co-primary efficacy end point (biopsy-proven acute rejection [BPAR], graft loss, or death from randomization to month 12) was 10.3% with EVR/rTAC and 5.8% with sTAC/MMF (difference 4.4%; P = .417). BPAR occurred in 9.6% and 5.6% of patients, respectively. Patient and renal allograft survival were 100%. The co-primary end point of mean estimated glomerular filtration rate at month 12 was 76.2 mL/min/1.73 m2 with EVR/rTAC and 72.5 mL/min/1.73 m2 for sTAC/MMF (difference 3.8 mL/min/1.73m2 ; P = .49). One EVR/rTAC patient developed posttransplant lymphoproliferative disease. Longitudinal growth and sexual maturation were equivalent between groups. The randomized drug regimen was discontinued in 34.6% and 13% of patients in the EVR/rTAC and sTAC/MMF groups, respectively (P = .024), and discontinued due to adverse events/infections in 25.0% and 11.1% of patients (P = .062). In conclusion, early conversion of pediatric kidney transplant patients from TAC, MMF, and steroids to EVR/rTAC and steroid withdrawal maintains immunosuppressive efficacy and preserves renal function.