Stephen D Marks

University College London | UCL · UCL GOS ICH

Introduction Continuing education should be an integral element in GOSH’s support for children to enable them to reach their life goals and to fulfill their potential. Research by Public Health England identifies that education is one of the key social determinants of future health and yet national legislative and statutory duties around education...

Introduction Renal transplantation remains the best modality of renal replacement therapy in children with end stage kidney disease, the majority of whom have congenital anomalies of the kidneys and urinary tract (CAKUT). Febrile urinary tract infections (UTI) can cause acute kidney injury (AKI) and worsen chronic kidney disease (CKD). After renal...

The cover image is based on the Original Article* Efficacy and safety of tacrolimus in de novo pediatric transplant recipients randomized to receive immediate‐ or prolonged‐release tacrolimus by Karel Vondrak & Nasrullah Undre** et al., https://doi.org/10.1111/ctr.13698.***

Objectives: IgA vasculitis (IgAV, formerly known as Henoch-Schönlein purpura) is the most common cause of systemic vasculitis in childhood. To date, there are no internationally agreed, evidence-based guidelines concerning the appropriate diagnosis and treatment of IgAV in children. Accordingly, treatment regimens differ widely. The European initi...

Objectives: Renal allograft thrombosis is an important cause of early renal allograft loss. A previous study from our unit showed thrombosis rates in patients who received heparin that were similar to those who did not receive any thromboprophylaxis. This study evaluated the impact of aspirin prophylaxis on renal allograft thrombosis rates in pedi...

Background and aims: This multicenter trial compared immediate-release tacrolimus (IR-T) versus prolonged-release tacrolimus (PR-T) in de novo kidney-, liver-, and heart-transplant recipients aged <16 years. Each formulation had similar pharmacokinetic (PK) profiles. Follow-up efficacy and safety results are reported herein. Materials and methods...

There are limited clinical data regarding prolonged‐release tacrolimus (PR‐T) use in pediatric transplant recipients. This Phase 2 study assessed the efficacy and safety of PR‐T in stable pediatric kidney, liver, and heart transplant recipients (aged ≥5–≤16 years) over 1 year following conversion from immediate‐release tacrolimus (IR‐T), on a 1:1 m...

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 recor...

Background Rituximab is a chimeric IgG1 monoclonal antibody that depletes B cells for the treatment of several conditions including autoimmune diseases. It is not licensed for use in children but administered off-label. This study aimed to quantify the effect of rituximab on B cell depletion in children with autoimmune diseases and to optimise the...

Background Mono-allelic mutation in tumor necrosis factor alpha induced protein 3 (TNFAIP3) has been found to cause haploinsufficiency of A20 protein, the cause of an early-onset auto inflammatory disease resembling Behcets’s disease (BD). Single nucleotide polymorphism in TNFAIP3 may also contribute to susceptibility to systemic lupus erythematosu...

Background The medium used in transporting donor kidneys is susceptible to bacterial growth. Practice in sending transport medium fluid(TMF) cultures differs between paediatric renal transplant centres. There is no consensus on which prophylactic antibiotic, if any, should be used and lack of published data on TMF cultures for paediatric renal tran...

Aim Primary hyperoxaluria type 1(PH1) is a rare genetic paediatric disease with high morbidity and mortality and no universal evidence-based guidelines. Evidence in combined liver-kidney transplantation (CLKT) for PH1 in children is limited and variable. We report a case of a child with a complicated PH1 who to date, had unreported post-operative m...

Background In current practice, pediatric kidney transplant recipients receive large volumes of intravenous fluid intraoperatively to establish allograft perfusion, and further fluid to replace urinary and insensible losses postoperatively. Acute electrolyte imbalance can result, with potential for neurological sequelae. We aimed to determine the i...

This study was a Phase II, open‐label, multicenter, single‐arm, cross‐over study comparing the pharmacokinetics (PK) of tacrolimus in stable pediatric kidney, liver, or heart allograft recipients converted from immediate‐release tacrolimus (IR‐T) to prolonged‐release tacrolimus (PR‐T). In Days −30 to −1 of screening period, patients received their...

Objectives: The European initiative Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) aimed to optimize care for children with rheumatic diseases. Systemic vasculitides are very rare in children. Consequently, despite recent advances, paediatric-specific information is sparse. The lack of evidence-based recommendations is a...

This review reports the outcomes of paediatric renal transplantation in the United Kingdom over the last 25 years. UK Transplant Registry data on 3,236 paediatric renal transplants performed between 1 January 1992 and 31 December 2016 were analysed. Significant improvements in HLA matching have been achieved; 84% of recipients received 000 or favou...

Phase 2, parallel‐group, multicenter, open‐label, 4‐week study, comparing PK of PR‐T vs IR‐T in de novo pediatric patients undergoing primary kidney, liver, or heart transplantation. Patients randomized 1:1 to receive once daily, PR‐T‐, or twice‐daily, IR‐T‐based regimens; dose adjustments permitted after Day 1. Twenty‐four‐hour PK profiles collect...

Objectives 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 (pRTR). Methods Data were obtained from the UK Transplant Registry (NHS Blood and Transplant) on all children (aged <18 years) who received a kidney only tran...

Background PCC/PGL are rare in children with an annual incidence of 0.2 and 0.3 per million in the 5–9 and 10–14 year age groups respectively. Most result from a genetic predisposition and represent a significant management challenge. Aims To provide the first interdisciplinary national management guidelines using the AGREEII framework for CYP wit...

Background Rituximab is a chimeric IgG-1 monoclonal antibody that depletes B cells, aiding in the treatment of several conditions including autoimmune and immunodeficiency diseases. It is not licensed for use in children but administered off-label. The current study aimed to identify the pharmacodynamics of rituximab in children with immune disorde...

Introduction There is increasing evidence of good short and medium term outcomes for ABO incompatible (ABOi) and HLA incompatible (HLAi) with pre-transplant positive crossmatches in paediatric practice. However, there are concerns regarding the higher risks of infective complications and antibody-mediated rejections. The aim of this paper is to sho...

Introduction Pre-emptive living donor renal transplantation is the gold standard treatment for children with end-stage kidney disease (ESKD). Despite this, many children spend years on dialysis before proceeding to transplantation. The aim of this study was to investigate access to paediatric renal transplantation and barriers within the process....

Introduction Effective postoperative pain management is important following paediatric renal transplant (pRT). Currently, the mainstay of pain control at Great Ormond Street Hospital (GOSH) is opioid analgesia. A previous audit demonstrated that patients on opioid analgesia on the renal ward at GOSH have significantly more postoperative nausea/vomi...

Background: A urine 'biomarker panel' comprising alpha-1-acid-glycoprotein, ceruloplasmin, transferrin and lipocalin-like-prostaglandin-D synthase performs to an 'excellent' level for lupus nephritis identification in children cross-sectionally. The aim of this study was to assess if this biomarker panel predicts lupus nephritis flare/remission lo...

Phase 2, parallel‐group, multicenter, open‐label, 4‐week study, comparing PK of PR‐T vs IR‐T in de novo pediatric patients undergoing primary kidney, liver, or heart transplantation. Patients randomized 1:1 to receive once daily, PR‐T‐, or twice‐daily, IR‐T‐based regimens; dose adjustments permitted after Day 1. Twenty‐four‐hour PK profiles collect...

Introduction: To rapidly make a diagnosis can be of paramount importance in the rare case of neonatal end-stage kidney disease. Material and methods: We present a girl born at 39 + 1 weeks of gestation to maternal primigravida without consanguinity. The antenatal ultrasounds were normal, including third trimester ultrasounds. She had a birth weight...

Introduction: PCC and PGL are rare in CYP. National children’s registry data reveal an annual incidence of 0.2 and 0.3 per million in 5-9 and 10-14 year age groups respectively. Almost all result from a genetic predispo- sition, can present with non-specific symptoms, and represent a signifi- cant management challenge. Material and methods: AGREEII...

With the increasing need for kidney transplantation in the paediatric population and changing donor demographics, children without a living donor option will potentially be offered an adult deceased donor transplant of marginal quality. Given the importance of long-term graft survival for paediatric recipients, consideration is now being given to k...

Objective: The authors investigated a novel application of patient-specific three-dimensional (3D) printing, to enhance preoperative, multidisciplinary planning in complex, living-donor pediatric renal transplantation. Summary background data: For children with end-stage kidney disease, the transplantation of adult-sized, living-donor kidneys in...

In a 12‐month, multicenter, open‐label study, 106 children were randomized at 4–6 weeks after kidney transplantation to switch to everolimus with reduced TAC (EVR/rTAC) and steroid elimination from month 5 post‐transplant or to continue standard tacrolimus with mycophenolate mofetil (sTAC/MMF) and steroids. The cumulative incidence of a co‐primary...

Despite the advances in renal transplantation over the last decades, chronic allograft dysfunction remains the largest concern for patients, their families, clinicians and other members of the multi-disciplinary team. Although we have made progress in improving patient and renal allograft survival within the first year after transplantation, the ra...

Histopathological diagnosis of acute antibody mediated rejection in children and outcomes when applying the updated Banff 2013 classification

In 2016, 964 children and young people aged less than 18 years were receiving long-term renal replacement therapy (RRT) for established renal failure (ERF) at UK paediatric nephrology centres. A total of 125 incident patients under 18 years commenced RRT. At the census date (31 December 2016), 77% of prevalent paediatric patients aged ,16 years had...

In 2016, the median height z-score for prevalent paediatric patients on dialysis was -1.8 and -1.1 for those with a functioning transplant (p < 0.0001). The median weight z-score for children receiving dialysis in 2016 was -1.2 compared with -0.2 for children with a functioning transplant. The median systolic blood pressure (SBP) z-score for transp...

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...

Background: The outcome of organs which have been declined for paediatric recipients is not known. This study aimed to determine the outcome of kidneys initially declined for paediatric recipients and establish renal allograft survival in kidneys that were eventually transplanted. Methods: Data were obtained from the UK Transplant Registry for a...

Background: Current reliance on clinical, laboratory and Doppler ultrasound (DUS) parameters for monitoring kidney transplant perfusion in the immediate post-operative period in children risks late recognition of allograft hypoperfusion and vascular complications. Near-infrared spectroscopy (NIRS) is a real-time, non-invasive technique for monitor...

Multiple perioperative variables have been shown in existing literature to influence long‐term outcomes of pediatric RTx, such as allograft survival. Their impact on short‐term outcomes is not as well‐documented. This case series aims to investigate the effects of nine perioperative variables on two short‐term outcomes in pRTR: 1‐week post‐operativ...

Pre-emptive living donor renal transplantation improves the morbidity and mortality of children with end stage kidney disease and is widely accepted as the gold standard for renal replacement therapy. As the accessibility to transplantation improves, its success is underpinned by the evolving importance of renal allograft matching and the principle...

OS of tacrolimus prepared from tacrolimus powder is not licensed for children. A licensed GF for OS allows flexibility for body weight‐based dose adjustments. This study aimed at exploring the efficacy of conversion from OS to the GF of tacrolimus in stable pediatric renal transplant recipients. Records of 25 pediatric renal transplant recipients a...

To promote the standardization of nephro-uroradiological terms used in children, the European Society of Paediatric Radiology uroradiology taskforce wrote a detailed glossary. This work has been subsequently submitted to European experts in pediatric urology and nephrology for discussion and acceptance to improve the quality of radiological reports...

Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with "operational tolerance" and chronic rejection (CR), independently and within the context of 88 tolerance-associated genes. Associations with cellular types were explored. Peripheral whole-blood gene-expression levels (RT-...

Background: Avoidance of vaccine-preventable infections in paediatric renal allograft recipients is of utmost importance. However, the development and maintenance of protective vaccination titres may be impaired in this patient population owing to their need for immunosuppressive medication. Methods: In the framework of the Cooperative European...

Initial complement antigenic levels. (A) C3. Normal in 76% of patients. (B) C4. Normal in 71% of patients. (C) Factor I. Normal in all patients. The dashed lines represent the lower limit of the normal ranges.

C4 level and factor H (FH) autoantibody circulating immune complexes. RU, relative units.

Outcome according to dialysis requirement at presentation; 75% of patients who required dialysis within 1 week of presentation fully recovered renal function. *Defined as dialysis within the first week of presentation. **Defined as recurrence >1 month after presentation and >15 days after disease remission. †Management: supportive: 1, PEX: 1. ‡Mana...

Kaplan-Meier survival curve showing probability of renal survival. Established renal failure developed in 35% of patients, and in all cases, this occurred at the first presentation of atypical hemolytic uremic syndrome. There were no deaths.

Initial titers of factor H autoantibody (aFH), circulating immune complexes (CiC), and autoantibody reactivity with factor H–related proteins 1 to 5 (positive threshold >100 relative units).

Serum creatinine and platelet values at presentation.

Comparison with other cohorts.

Autoantibody reactivity with short factor H fragments.

Treatment modality and resultant renal function.

Background: Because infections constitute a major cause of morbidity and mortality in paediatric renal allograft recipients, avoidance of preventable systemic infections by vaccination before transplantation is of utmost importance. However, data on the completeness of vaccinations and factors associated with incomplete vaccination coverage are sc...

Background Lack of blood group compatible donors and sensitisation resulting in development of broad spectrum anti-HLA antibodies, is an increasing problem making it difficult for some children with renal disease to undergo transplantation. We have set up the first antibody incompatible transplant programme for children in the UK. Methods We descr...

Background Kidneys offered for paediatric transplantation may be declined for a variety of donor or recipient specific factors. The aims of this study were to determine the outcome of kidneys declined for paediatric recipients and establish renal allograft survival in kidneys that were eventually transplanted. Methods Data from NHS Blood and Trans...

Background To investigate our hypothesis that non-invasive cortical renal blood flow (cRBF) measurements using functional magnetic resonance imaging (MRI) arterial spin labelling (ASL) are sensitive biomarkers of early damage of the transplanted kidney in paediatric renal transplant recipients (pRTR). Methods Prospective study of pRTR undergoing M...

Introduction: We have previously shown that children who developed de novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) had greater decline in allograft function. We hypothesised that patients with complement-activating DSA would have poorer renal allograft outcomes. Methods: A total of 75 children developed DSA in the original...

Post-infectious glomerulonephritis (PIGN) is one of the most common causes of acute glomerulonephritis in children. Although post-streptococcal glomerulonephritis (PSGN) is still common, there is a wide spectrum of causative agents of PIGN. Non-streptococcal organisms are emerging as the main aetiological agents in high-income countries. Nephritis-...

Lupus nephritis (LN) occurs in 50%-60% of patients with childhood-onset systemic lupus erythematosus (cSLE), leading to significant morbidity. Timely recognition of renal involvement and appropriate treatment are essential to prevent renal damage. The Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative aimed to gene...

A total of 941 children and young people aged <18 years with established renal failure (ERF) were receiving treatment at paediatric nephrology centres in 2015. At the census date (31st December 2015), 75.3% of prevalent paediatric patients aged <16 years had a functioning kidney transplant, 13.0% were receiving haemodialysis (HD) and 11.7% were rec...

The median height z-score for paediatric patients on dialysis in 2015 was-1.8 and for those with a functioning transplant-1.2. Children transplanted before the age of 12 years improved their height z-score over the subsequent five years, whereas those older than 12 years maintained their height z-score, with all transplanted patients having a simil...

To promote the standardization of nephro-uroradiological terms used in children, the European Society of Pediatric Radiology uroradiology taskforce wrote a detailed glossary. This work has been subsequently submitted to European experts in pediatric urology and nephrology for discussion and acceptance to improve the quality of radiological reports...

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 Ki...

Childhood-onset systemic lupus erythematosus (cSLE) is a rare, multisystem and potentially life-threatening autoimmune disorder with significant associated morbidity. Evidence-based guidelines are sparse and management is often based on clinical expertise. SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) was launched to opt...

P368 Introduction: Idiopathic musculoskeletal pain (IMP) is related to a negative impact in the quality of life of children and adolescents sleep problems and psychosocial factors seem to be involved in its pathogenesis, which is not fully known. Restless legs syndrome (RLS), periodic limb movements (PML) and sleep problems were observed in adults...

Antiphospholipid syndrome (APS) is rare in children, and evidence-based guidelines are sparse. Consequently, management is mostly based on observational studies and physician's experience, and treatment regimens differ widely. The Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative was launched to develop diagnostic...

Prophylactic ureteric stenting in renal transplantation reduces major urological complications (MUCs). There is however morbidity related to the indwelling duration of a stent, we aimed to determine the optimal duration for stents in this clinical setting. Patients (aged 2-75 years) from 6 UK hospitals undergoing renal transplantation were recruite...

Background Transplantation is the treatment of choice for paediatric renal recipients. However, there are increased challenges in small (<20 kg) children who have complex abnormalities of the abdominal vascular system (aorta and inferior vena cava [IVC]). In this context surgical feasibility and planning is informed by review of medical images. Con...

Renal transplantation is the therapy of choice in children with ESKD. Radiological investigations are required in both pre- and post-transplant assessment, although there is paucity of both consensus-based statements and evidence-based imaging guidelines in pediatric renal transplantation. The phases of pediatric ESKD management that require imagin...

Steroid Resistant Nephrotic Syndrome (SRNS) in children and young adults has differing etiologies with monogenic disease accounting for 2.9-30% in selected series. Using whole exome sequencing we sought to stratify a national population of children with SRNS into monogenic and non-monogenic forms, and further define those groups by detailed phenoty...

Background: Children with end-stage kidney disease may have co-existing iatrogenic or congenital vascular anomalies making transplantation difficult. We describe our approach in 5 recipients with vascular anomalies and significant co-morbidities, including one case of blood group incompatibility. Methods: Five children aged 3 - 17 (median 7) yea...

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of disorders characterized by necrotizing inflammation of the small to medium vessels in association with autoantibodies against the cytoplasmic region of the neutrophil. Included in this definition are granulomatosis with polyangiitis (GPA, formerly known as...

Data S1: Materials and methods. Table S1: Genes whose expression is affected by immunosuppressive drugs (Excel file attached at the end). Table S2: Distribution of drug regimen in stable patients. Table S3: Detailed clinical description of GAMBIT tolerant patients. GAMBIT, Genetic Analysis of Molecular Biomarkers of Immunological Tolerance. Tab...

Background New-onset diabetes after transplantation (NODAT) is a significant co-morbidity following kidney transplantation. Lower post-transplant serum magnesium levels have been found to be an independent risk factor for NODAT in adult kidney transplant recipients. Methods We undertook a retrospective analysis of risk factors for NODAT in pediatri...

Background: Increased plasma cell infiltration in renal allograft biopsies is a rare finding associated with poor outcome in adult renal transplant recipients. The clinical impact of increased plasma cell infiltrates in paediatric renal transplant recipients (pRTR) remains unknown. Methods: We conducted a retrospective case-control study from Ap...

Objectives Renovascular disease (RVD) is found in about 10 % of secondary childhood hypertension. Digital subtraction angiography (DSA) is the gold standard to diagnose RVD. Non-invasive imaging methods like Doppler ultrasound (US), magnetic resonance angiography (MRA), and computed tomography angiography (CTA) are increasingly used. Our aim was to...