Publications by authors named "Ben C Reynolds"

19 Publications

  • Page 1 of 1

Treatment and long-term outcome in primary nephrogenic diabetes insipidus.

Nephrol Dial Transplant 2020 Dec 26. Epub 2020 Dec 26.

Department of Renal Medicine, University College London, London,UK.

Background: Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome.

Methods: Paediatric and adult nephrologists contacted through European professional organizations entered data in an online form.

Results: Data were collected on 315 patients (22 countries, male 84%, adults 35%). Mutation testing had been performed in 270 (86%); pathogenic variants were identified in 258 (96%). The median (range) age at diagnosis was 0.6 (0.0-60) years and at last follow-up 14.0 (0.1-70) years. In adults, height was normal with a mean (standard deviation) score of -0.39 (±1.0), yet there was increased prevalence of obesity (body mass index >30 kg/m2; 41% versus 16% European average; P < 0.001). There was also increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (32%) and adults (48%). Evidence of flow uropathy was present in 38%. A higher proportion of children than adults (85% versus 54%; P < 0.001) received medications to reduce urine output. Patients ≥25 years were less likely to have a university degree than the European average (21% versus 35%; P = 0.003) but full-time employment was similar. Mental health problems, predominantly attention-deficit hyperactivity disorder (16%), were reported in 36% of patients.

Conclusion: This large NDI cohort shows an overall favourable outcome with normal adult height and only mild to moderate CKD in most. Yet, while full-time employment was similar to the European average, educational achievement was lower, and more than half had urological and/or mental health problems.
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http://dx.doi.org/10.1093/ndt/gfaa243DOI Listing
December 2020

Thromboprophylaxis in congenital nephrotic syndrome: 15-year experience from a national cohort.

Pediatr Nephrol 2020 Oct 21. Epub 2020 Oct 21.

University of Glasgow, Glasgow, UK.

Introduction: Congenital nephrotic syndrome (CNS) is an ultra-rare disease associated with a pro-thrombotic state and venous thromboembolisms (VTE). There is very limited evidence evaluating thromboprophylaxis in patients with CNS. This study aimed to determine the doses and duration of treatment required to achieve adequate thromboprophylaxis in patients with CNS.

Methods: From 2005 to 2018 children in Scotland with a confirmed genetic or histological diagnosis of CNS were included if commenced on thromboprophylaxis. The primary study endpoint was stable drug monitoring. Secondary outcomes included VTE or significant haemorrhage.

Results: Eight patients were included; all initially were commenced on low-molecular weight heparin (enoxaparin). Four patients maintained therapeutic anti-Factor Xa levels (time 3-26 weeks, dose 3.2-5.07 mg/kg/day), and one patient developed a thrombosis (Anti-Factor Xa: 0.27 IU/ml). Four patients were subsequently treated with warfarin. Two patients maintained therapeutic INRs (time 6-11 weeks, dose 0.22-0.25 mg/kg/day), and one patient had two bleeding events (Bleed 1: INR 6, Bleed 2: INR 5.5).

Conclusions: Achieving thromboprophylaxis in CNS is challenging. Similar numbers of patients achieved stable anticoagulation on warfarin and enoxaparin. Enoxaparin dosing was nearly double the recommended starting doses for secondary thromboprophylaxis. Bleeding events were all associated with supra-therapeutic anticoagulation.
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http://dx.doi.org/10.1007/s00467-020-04793-zDOI Listing
October 2020

UK national study of barriers to renal transplantation in children.

Arch Dis Child 2020 Apr 2. Epub 2020 Apr 2.

Paediatric Nephrology, Great Ormond Street Hospital For Children NHS Foundation Trust, London, UK.

Aims: To investigate access to paediatric renal transplantation and examine potential barriers within the process.

Methods: Cross-sectional, multicentre, observational study where paediatric nephrology centres in the UK were requested to provide data on transplantation plans for all children (<18 years) with end-stage kidney disease (ESKD).

Results: 308 children with ESKD were included in this study from 12 out of 13 UK paediatric nephrology centres. 139 (45%) were being prepared for living donor transplantation and 82 (27%) were listed for deceased donor transplantation. The most common cited factors delaying transplantation from occurring in children were disease factors (36%), donor availability (27%) and size of the child (20%). Psychosocial factors were listed as a barrier in 19% of children.

Conclusions: In this study we have documented the main barriers to renal transplantation in children. Some identified factors may be modifiable through local or national intervention, including donor availability and patient psychosocial factors.
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http://dx.doi.org/10.1136/archdischild-2019-318272DOI Listing
April 2020

Direct venous pressure assessment pre-renal transplantation to optimise graft venous drainage.

Pediatr Nephrol 2020 08 13;35(8):1525-1528. Epub 2019 Dec 13.

Department of Paediatric Nephrology, Royal Hospital for Children, 1345 Govan Road, Glasgow, G51 4TF, UK.

Background: Renal transplantation is the modality of choice in the treatment of end-stage kidney disease. Surgically challenging aspects of renal transplantation may include creation of vascular anastomoses where there is complex vascular anatomy. We present a paediatric case of living-related donor (LRD) renal transplantation in whom direct intravenous pressure measurement guided the management of the vascular anastomoses in the context of inferior vena cava (IVC) obstruction.

Case-diagnosis/treatment: During venography for transplant assessment, 150 mL of 0.9% sodium chloride was infused for over 20 s into well-developed collateral paravertebral veins to simulate the anticipated high-volume venous return from an implanted kidney. Direct venous pressure measurements were 20 mmHg in the right paravertebral vein and 19 mmHg in the left paravertebral vein. We were reassured by this result that the collateralised venous system could sustain the high venous drainage and maintain the arteriovenous (AV) gradient required for adequate graft perfusion. Intra-operative measurement at the time of transplantation, following release of venous clamps, of 22 mmHg supported the validity of this approach.

Conclusions: In children with complex venous anatomy pre-transplant, direct intravenous pressure measurement may provide a useful adjunct in deciding which vessel is most suitable for transplant anastomosis.
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http://dx.doi.org/10.1007/s00467-019-04443-zDOI Listing
August 2020

Embryonal precursors of Wilms tumor.

Science 2019 12;366(6470):1247-1251

Wellcome Sanger Institute, Hinxton CB10 1SA, UK.

Adult cancers often arise from premalignant clonal expansions. Whether the same is true of childhood tumors has been unclear. To investigate whether Wilms tumor (nephroblastoma; a childhood kidney cancer) develops from a premalignant background, we examined the phylogenetic relationship between tumors and corresponding normal tissues. In 14 of 23 cases studied (61%), we found premalignant clonal expansions in morphologically normal kidney tissues that preceded tumor development. These clonal expansions were defined by somatic mutations shared between tumor and normal tissues but absent from blood cells. We also found hypermethylation of the locus, a known driver of Wilms tumor development, in 58% of the expansions. Phylogenetic analyses of bilateral tumors indicated that clonal expansions can evolve before the divergence of left and right kidney primordia. These findings reveal embryonal precursors from which unilateral and multifocal cancers develop.
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http://dx.doi.org/10.1126/science.aax1323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914378PMC
December 2019

Prevalence of Acute Kidney Injury in Neonates with Congenital Diaphragmatic Hernia.

Neonatology 2020 22;117(1):88-94. Epub 2019 Oct 22.

Department of Paediatric Nephrology, Royal Hospital for Children, Glasgow, United Kingdom.

Background: Congenital diaphragmatic hernia (CDH) often presents with severe cardio-respiratory impairment in the neonatal period. Affected infants may be exposed to multiple nephrotoxic insults, predisposing them to acute kidney injury (AKI). The prevalence of AKI in a CDH cohort has not previously been described.

Objectives: The primary aim of this study was to quantify the prevalence of AKI in patients with CDH treated in a single national centre. Secondarily, we investigated the association between AKI, select neonatal outcomes, and recognised AKI risk factors.

Methods: This was a retrospective analysis of all patients with CDH treated at our regional neonatal surgical centre between September 2011 and December 2017. Data was collected on demographics, CDH Study Group stage (size), laboratory and physiological parameters, medications, mortality, and duration of hospitalisation. AKI severity was stratified using the modified paediatric RIFLE criteria, determined by comparing the percentage increase in serum creatinine from baseline. Statistical analysis was performed using Fisher's exact and Pearson's χ2 tests for parametric analysis and Mann-Whitney U testing for non-parametric analysis.

Results: Fifty-four CDH patients met the inclusion criteria, 37% of whom developed AKI. The development of AKI was significantly associated with larger CDH defect (type C/D; p = 0.014), extracorporeal membranous oxygenation support (p = 0.003), patch repair (p = 0.004), and exposure to vancomycin, corticosteroids and diuretics (p = 0.004, p = 0.007, and p ≤ 0.001, respectively). There was no statistical association between AKI and gentamicin administration, umbilical arterial catheter insertion, or significant infection. Prolonged hospitalisation and patient mortality were significantly associated with AKI (p = 0.01 and p = 0.001, respectively).

Conclusions: AKI is common in CDH cases treated in our centre and is associated with adverse outcomes. Potentially modifiable risk factors include nephrotoxic medication exposure. Prevention and early recognition of contributory factors for AKI may improve outcomes in CDH.
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http://dx.doi.org/10.1159/000503293DOI Listing
November 2020

Extended initial course of prednisolone did not improve clinical outcomes in steroid-sensitive nephrotic syndrome.

Arch Dis Child Educ Pract Ed 2020 06 16;105(3):189. Epub 2019 Oct 16.

Paediatric Renal Unit, Royal Hospital for Children, Glasgow, UK.

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http://dx.doi.org/10.1136/archdischild-2019-318060DOI Listing
June 2020

Low-dose rituximab is no less effective for nephrotic syndrome measured by 12-month outcome.

Pediatr Nephrol 2019 05 18;34(5):855-863. Epub 2018 Dec 18.

Department of Paediatric Nephrology, Royal Hospital for Children, 1345 Govan Road, Glasgow, G51 4TF, UK.

Objective: Rituximab is an effective treatment for children with steroid dependent or frequently relapsing nephrotic syndrome. The optimum dosing schedule for rituximab has not been established. We hypothesized that a single low dose of 375 mg/m would have comparable outcomes to higher doses in reducing the frequency of relapse and time to B cell reconstitution.

Methods: We conducted a multicenter retrospective observational cohort study of children with steroid-sensitive frequently relapsing nephrotic syndrome. Data were extracted from clinical records including the dates of diagnosis, treatment, relapses, the use of concomitant immunosuppression, and lymphocyte subset profiling. Patients treated earlier received variable doses of rituximab, although typically two doses of 750 mg/m. Later, patients received the current regimen of a single dose of 375 mg/m. The primary outcome was an absence of clinically confirmed relapse 12 months following rituximab administration. Secondary outcomes were median time to relapse, probability of being relapse-free at 6 and 24 months and time to reconstitution of CD19 B cells.

Results: Sixty patients received 143 courses of rituximab. Seven different dosing regimen strategies were used, ranging between 375 and 750 mg/m per dose, with administration of 1-4 doses. There was no significant difference in event-free survival at 12 months between dosing strategies. The median time to reconstitution of B cells was not significantly different between groups.

Conclusions: Use of a single low-dose regimen of rituximab in the management of frequently relapsing nephrotic syndrome does not affect the probability of relapse at 12 months or time to B cell reconstitution compared to a conventional higher dose.
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http://dx.doi.org/10.1007/s00467-018-4172-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424916PMC
May 2019

Sensitization assessment before kidney transplantation.

Transplant Rev (Orlando) 2017 01 8;31(1):18-28. Epub 2016 Oct 8.

University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Kidney transplantation is the treatment of choice for patients with end stage renal disease to optimize survival, freedom from morbidity and quality of life. A fundamental aspect of the pre-transplant assessment is a thorough understanding of their immunological history and prior exposures, so that the immunological risk from a given donor can be estimated, if not quantified, in order to guide interventions to optimize transplant access and success. The methodologies available to complete this assessment have evolved rapidly, with flow cytometric based analyses now standard in many laboratories, availability of comprehensive molecular methods for HLA typing of both donors and recipients, and an increasing recognition of the vital dialogue that must occur between the HLA laboratory and transplant clinicians. This review considers the pre-transplant histocompatibility assessment journey that a recipient undertakes, from initial referral through transplantation, discussing the methodologies used, the benefits and limitations offered by current technologies, and reviewing the basics of interpretation.
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http://dx.doi.org/10.1016/j.trre.2016.10.001DOI Listing
January 2017

Exposure to inflammatory cytokines selectively limits GM-CSF production by induced T regulatory cells.

Eur J Immunol 2014 Nov 1;44(11):3342-52. Epub 2014 Oct 1.

MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.

Interest in manipulating the immunosuppressive powers of Foxp3-expressing T regulatory cells as an immunotherapy has been tempered by their reported ability to produce proinflammatory cytokines when manipulated in vitro, or in vivo. Understanding processes that can limit this potentially deleterious effect of Treg cells in a therapeutic setting is therefore important. Here, we have studied this using induced (i) Treg cells in which de novo Foxp3 expression is driven by TCR-stimulation in vitro in the presence of TGF-β. We show that iTreg cells can produce significant amounts of three proinflammatory cytokines (IFN-γ, GM-CSF and TNF-α) upon secondary TCR stimulation. GM-CSF is a critical T-cell derived cytokine for the induction of EAE in mice. Despite their apparent capacity to produce GM-CSF, myelin autoantigen-responsive iTreg cells were unable to provoke EAE. Instead, they maintained strong suppressive function in vivo, preventing EAE induction by their CD4+ Foxp3- counterparts. We identified that although iTreg cells maintained the ability to produce IFN-γ and TNF-α in vivo, their ability to produce GM-CSF was selectively degraded upon antigen stimulation under inflammatory conditions. Furthermore, we show that IL-6 and IL-27 individually, or IL-2 and TGF-β in combination, can mediate the selective loss of GM-CSF production by iTreg cells.
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http://dx.doi.org/10.1002/eji.201444687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257504PMC
November 2014

Bones, stones, moans and groans: hypercalcaemia revisited.

Arch Dis Child Educ Pract Ed 2015 Feb 5;100(1):44-51. Epub 2014 Aug 5.

Department of Paediatric Endocrinology and Diabetes, Great North Children's Hospital, Newcastle upon Tyne, UK.

Disorders of calcium homeostasis are uncommon but important because of the broad spectrum of potential underlying causes that lie on a spectrum from the benign to the life-threatening. Paediatricians may find them challenging because they do not arise often enough for the investigative approach to be second nature. We report a 4-year-old with acute onset profound hypercalcaemia. We focus on an approach to the clinical problem that is based on the potential organ systems affected, namely the gut, bone and kidney. Key biochemical parameters that may help the paediatric team to reach a diagnosis are discussed, as well as important components of acute management.
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http://dx.doi.org/10.1136/archdischild-2013-305406DOI Listing
February 2015

One good match permits another-why HLA-matched blood transfusion makes sense.

Clin Kidney J 2013 Aug;6(4):452

Department of Paediatric Nephrology , Great North Children's Hospital , Newcastle-upon-Tyne NE1 4LP , UK.

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http://dx.doi.org/10.1093/ckj/sft074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898346PMC
August 2013

Focal segmental glomerulosclerosis, Coats'-like retinopathy, sensorineural deafness and chromosome 4 duplication: a new association.

Pediatr Nephrol 2010 Aug 27;25(8):1551-4. Epub 2010 Feb 27.

Renal Unit, Royal Hospital for Sick Children, Glasgow, G3 8SJ, UK.

We describe the novel association in a girl of nephrotic syndrome due to focal segmental glomerulosclerosis, bilateral sensorineural deafness, basal ganglia calcification, bilateral retinopathy similar to that seen in Coats' disease, with de novo duplication of a subtelomeric region of chromosome 4q35. The chromosomal duplication was identified during investigation of a possible association with features of fascio-scapulo-humeral dystrophy (FSHD). This duplication has not previously been reported with FSGS and adds to the expanding number of genetic associations with steroid-resistant nephrotic syndrome.
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http://dx.doi.org/10.1007/s00467-010-1474-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887537PMC
August 2010

Multifocal multi-organ ischaemia and infarction in a preterm baby due to maternal intravenous cocaine use: a case report.

J Med Case Rep 2009 Dec 10;3:9324. Epub 2009 Dec 10.

Neonatal Unit, Princess Royal Maternity Hospital, Alexandra Parade, Glasgow, UK.

Introduction: Although the adverse effects of cocaine use in pregnancy are well recognised, we believe this case highlights the importance of considering the route of administration, and suggests the possibility of multifocal damage relating to intravenous use.

Case Presentation: A Caucasian female baby of 29-weeks' gestation was spontaneously delivered and subsequently developed multi-organ failure considered unrelated to simple prematurity. Intensive care was re-orientated following the development of massive intraventricular haemorrhage.

Conclusion: This case illustrates the need for regular cranial ultrasound in babies of pregnancies at risk due to intravenous cocaine use and also the necessity of counselling women who misuse cocaine in the antenatal period. As such, this article will be of most interest to paediatric and obstetric staff.
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http://dx.doi.org/10.1186/1752-1947-3-9324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803847PMC
December 2009

Multifocal multi-organ ischaemia and infarction in a preterm baby due to maternal intravenous cocaine use: a case report.

J Med Case Rep 2009 Sep 14;3:9259. Epub 2009 Sep 14.

Introduction: Although the adverse effects of cocaine use in pregnancy are well recognised, we believe this case highlights the importance of considering the route of administration, and suggests the possibility of multifocal damage relating to intravenous use.

Case Presentation: A Caucasian female baby of 29-weeks' gestation was spontaneously delivered and subsequently developed multi-organ failure considered unrelated to simple prematurity. Intensive care was re-orientated following the development of massive intraventricular haemorrhage.

Conclusion: This case illustrates the need for regular cranial ultrasound in babies of pregnancies at risk due to intravenous cocaine use and also the necessity of counselling women who misuse cocaine in the antenatal period. As such, this article will be of most interest to paediatric and obstetric staff.
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http://dx.doi.org/10.4076/1752-1947-3-9259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2767157PMC
September 2009

Silicon in the Earth's core.

Nature 2007 Jun;447(7148):1102-6

Department of Earth Sciences, University of Oxford, South Parks Road, Oxford OX1 3PR, UK.

Small isotopic differences between the silicate minerals in planets may have developed as a result of processes associated with core formation, or from evaporative losses during accretion as the planets were built up. Basalts from the Earth and the Moon do indeed appear to have iron isotopic compositions that are slightly heavy relative to those from Mars, Vesta and primitive undifferentiated meteorites (chondrites). Explanations for these differences have included evaporation during the 'giant impact' that created the Moon (when a Mars-sized body collided with the young Earth). However, lithium and magnesium, lighter elements with comparable volatility, reveal no such differences, rendering evaporation unlikely as an explanation. Here we show that the silicon isotopic compositions of basaltic rocks from the Earth and the Moon are also distinctly heavy. A likely cause is that silicon is one of the light elements in the Earth's core. We show that both the direction and magnitude of the silicon isotopic effect are in accord with current theory based on the stiffness of bonding in metal and silicate. The similar isotopic composition of the bulk silicate Earth and the Moon is consistent with the recent proposal that there was large-scale isotopic equilibration during the giant impact. We conclude that Si was already incorporated as a light element in the Earth's core before the Moon formed.
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http://dx.doi.org/10.1038/nature05927DOI Listing
June 2007

The impact of national guidelines on the assessment and management of acute paediatric asthma presenting at a tertiary children's emergency department.

Eur J Emerg Med 2007 Jun;14(3):142-6

Department of Medical Paediatrics, Royal Hospital for Sick Children, Edinburgh, UK.

Background: Recent Scottish Intercollegiate Guidelines Network/British Thoracic Society guidelines have highlighted best practice for asthma management. This study examines asthma management in a paediatric emergency setting before and after the publication of these guidelines.

Objectives: To assess the impact of Scottish Intercollegiate Guidelines Network/British Thoracic Society guidelines on asthma management.

Methods: Retrospective review of patient notes over two equivalent 2-month periods in 2002 and 2003. Main outcomes were documentation of clinical history, examination, investigation, treatment and discharge; and also the use of various treatment modalities in each case.

Results: One hundred and sixty-four children presented with asthma, 100 in 2002 and 64 in 2003. Documentation was adequate throughout, though better when nursing staff were responsible. Completeness of documentation was not related to seniority or discipline of medical staff. Measurement of peak flow was poor in both years. The 'doubling up' of inhaled steroid dose for acute episodes was the only aspect of management affected by publication of the guidelines, with significantly fewer patients receiving this in 2003 (P<0.0001).

Conclusions: Documentation within the centre is good but has potential for improvement. Guidelines have not impacted on this except when explicit statements are made regarding treatment.
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http://dx.doi.org/10.1097/MEJ.0b013e32801430b8DOI Listing
June 2007