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Background Kidney transplantation is the treatment of choice in chronic kidney disease (CKD) stage 5. It is often delayed in younger children until a target weight is achieved due to technical feasibility and historic concerns about poorer outcomes. Methods Data on all first paediatric (aged < 18 years) kidney only transplants performed in the United Kingdom between 1 January 2006 and 31 December 2016 were extracted from the UK Transplant Registry (n = 1,340). Children were categorised by weight at the time of transplant into those < 15 kg and those [greater than or equal to] 15 kg. Donor, recipient and transplant characteristics were compared between groups using chi-squared or Fisher's exact test for categorical variables and Kruskal-Wallis test for continuous variables. Thirty day, one-year, five-year and ten-year patient and kidney allograft survival were compared using the Kaplan-Meier method. Results There was no difference in patient survival following kidney transplantation when comparing children < 15 kg with those [greater than or equal to] 15 kg. Ten-year kidney allograft survival was significantly better for children < 15 kg than children [greater than or equal to] 15 kg (85.4% vs. 73.5% respectively, p = 0.002). For children < 15 kg, a greater proportion of kidney transplants were from living donors compared with children [greater than or equal to] 15 kg (68.3% vs. 49.6% respectively, p < 0.001). There was no difference in immediate graft function between the groups (p = 0.54) and delayed graft function was seen in 4.8% and 6.8% of children < 15 kg and [greater than or equal to] 15 kg respectively. Conclusions Our study reports significantly better ten-year kidney allograft survival in children < 15 kg and supports consideration of earlier transplantation for children with CKD stage 5. Graphical abstract, Author(s): Charles W. Pickles [sup.1] , Chloe Brown [sup.2] , Stephen D. Marks [sup.3] [sup.4] , Ben C. Reynolds [sup.5] , Nicos Kessaris [sup.6] [sup.4] , Jan Dudley [sup.7] Author [...]

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., Author(s): Ian K. Hewitt [sup.1] , Giovanni Montini [sup.2] [sup.3] , Stephen D. Marks [sup.4] [sup.5] Author Affiliations: (1) grid.518128.7, 0000 0004 0625 8600, Perth Children's Hospital, , Monash Avenue, [...]

Author(s): Lucy Plumb [sup.1] [sup.2] , Stephen D. Marks [sup.3] [sup.4] Author Affiliations: (1) grid.5337.2, 0000 0004 1936 7603, Population Health Sciences, University of Bristol Medical School, , Bristol, UK [...]

Survival of pediatric kidney transplant recipients has improved over the past six decades. However, adolescents and young adults still have the highest graft failure rates of any age group. There is a growing need for well-designed transition programs to ensure the successful integration of young adults into adult society with eventual transfer of care and management in adult transplant centers. In this review, we discuss the risk factors contributing to the high risk of kidney graft failure observed between 17 and 24 years of age, including the role of transfer from pediatric to adult care. We also address the unique challenges of adolescents with kidney transplant: the impact of chronic kidney disease on neurocognition, age-related changes in immune activity, and suboptimal adherence during the transition process. We then describe strategies to mitigate these risks by designing developmentally appropriate transition programs, and review the evidence supporting the benefits of well-designed multidisciplinary transition programs., Author(s): Mina Matsuda-Abedini [sup.1] , Stephen D. Marks [sup.2] [sup.3] , Bethany J. Foster [sup.4] [sup.5] [sup.6] Author Affiliations: (1) grid.42327.30, 0000 0004 0473 9646, Department of Pediatrics, University of [...]

Background Transplantation is widely considered the gold standard method of kidney replacement therapy. Despite compelling evidence for biological sexual dimorphisms, the role of donor and recipient sex matching in transplantation is undefined. Methods The UK historical cohort study explores the impact of donor and recipient sex on allograft survival, in children receiving their first deceased donor transplant. Nationwide registry data were collected for 1316 transplant procedures performed from January 1, 1999, to December 31, 2019. Results Male donor-male recipient transplantation occurred most frequently (35%), followed by female donor-male recipient (23%), male donor-female recipient (22%), and female donor-female recipient (20%). The median follow-up time was 7.03 years (IQR: 2.89-12.4 years), with a total of 10,326 person-years. Male donor-male recipients were associated with the highest 10-year kidney allograft survival (72.8% [95% CI 68.3-77.8]) and male donor-female recipients with the lowest (64% [95% CI 57.7-71.1]). Multivariable Cox regression demonstrated for male donor transplantation, the risk of kidney allograft failure was 1.46 times greater for female (compared to male) recipients, after adjusting for acquired recipient age, recipient/donor age at transplantation, mismatched HLA A/B/DR, waitlist time, cold ischemia time, CMV seropositivity, donor hypertension, and donor diabetes (HR 1.46 [95% CI. 1.06-2.01], p = 0.02). There was no evidence for an independent effect of donor or recipient sex in other combinations. Conclusion This study highlights the complex relationship between donor and recipient sex and pediatric kidney allograft survival, which require further mechanistic evaluation. Graphical abstract, Author(s): Nadeesha L Mudalige [sup.1] , Chloe Brown [sup.2] , Stephen D Marks [sup.1] [sup.3] Author Affiliations: (1) grid.83440.3b, 0000000121901201, NIHR Great Ormond Street Hospital Biomedical Research Centre, University College [...]

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., Author(s): Alasdair Bamford [sup.1] [sup.2] , Garth Dixon [sup.3] [sup.2] , Nigel Klein [sup.1] [sup.2] , Stephen D. Marks [sup.4] [sup.2] , Nicole Ritz [sup.5] [sup.6] , Steven B. Welch [...]

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., Author(s): Jelena Stojanovic [sup.1] , Anna Adamusiak [sup.2] , Aoife Waters [sup.1] , Neil J. Sebire [sup.3] , Nicos Kessaris [sup.2] , Nizam Mamode [sup.2] , Stephen D. Marks [sup.1] [...]

Background 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. Methods 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). Results 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). Conclusions 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., Author(s): Evgenia Preka [sup.1] [sup.2] , Thivya Sekar [sup.3] , Sergio C Lopez Garcia [sup.1] , Olivia Shaw [sup.4] , Nicos Kessaris [sup.5] , Nizam Mamode [sup.5] , Jelena Stojanovic [...]

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., Author(s): Louise Oni [sup.1] [sup.2] [sup.3] , Rachael D Wright [sup.1] , Stephen Marks [sup.4] [sup.5] , Michael W Beresford [sup.1] [sup.6] , Kjell Tullus [sup.4] [sup.5] Author Affiliations: (1) [...]

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post‐transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti‐CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision‐making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted. [ABSTRACT FROM AUTHOR]

Children with end-stage kidney disease should be offered the best chance for future survival which ideally would be a well-matched pre-emptive kidney transplant. Paediatric and adult practice varies around the world depending on geography, transplant allocation schemes and different emphases on living (versus deceased) donor renal transplantation. Internationally, paediatric patients often have priority in allocation schemes and younger donors are preferentially allocated to paediatric recipients. HLA matching can be difficult and may result in longer waiting times. Additionally, with improved surgical techniques and modern immunosuppressive regimens, how important is the contribution of HLA matching to graft longevity? In this review, we discuss the relative importance of HLA matching compared with donor quality; and long-term patient outcomes including re-transplantation rates. We share empirical evidence that will be useful for clinicians and families to make decisions about best donor options. We discuss why living donation still provides the best allograft survival outcomes and what to do in the scenario of a highly mismatched living donor., Author(s): Jon Jin Kim [sup.1] [sup.2] , Susan V Fuggle [sup.3] [sup.4] , Stephen D Marks [sup.5] [sup.6] Author Affiliations: (1) Department of Paediatric Nephrology, Nottingham Children's Hospital, , NG7 [...]

Author(s): Sarah Khweir [sup.1] [sup.2] , Louise McAlister [sup.1] , Stephen D Marks [sup.3] [sup.4] Author Affiliations: (1) grid.424537.3, 0000 0004 5902 9895, Dietetics Department, Great Ormond Street Hospital for [...]