Advanced chronic kidney disease among UK children.

The UK Renal Registry currently collects information on UK children with kidney failure requiring long-term kidney replacement therapy (KRT), which supports disease surveillance and auditing of care and outcomes; however, data are limited on children with chronic kidney disease (CKD) not on KRT. METHODS: In March 2020, all UK Paediatric Nephrology centres submitted data on children aged <16 years with severely reduced kidney function as of December 2019, defined as an estimated glomerular filtration rate <30 mL/min/1.73 m2. RESULTS: In total, 1031 children had severe CKD, the majority of whom (80.7%) were on KRT. The overall prevalence was 81.2 (95% CI 76.3 to 86.3) per million of the age-related population. CONCLUSIONS: The prevalence of severe CKD among UK children is largely due to a high proportion of children on long-term KRT. Expanding data capture to include children with CKD before reaching failure will provide greater understanding of the CKD burden in childhood.

Mechanical stress-related haemolysis in a paediatric haemodialysis patient.

Haemodialysis (HD) is a common kidney replacement therapy (KRT) used in the management of children with end-stage kidney disease (ESKD). We describe the case of a 2-year-old child who developed mechanical intraluminal haemolytic anaemia secondary to the acute angulation of the HD line. In contrast to reports of arteriovenous fistula-associated haemolysis, onset was insidious in nature and detected through review of subtle serial biochemical and haematological changes. Development of hyperbilirubinaemia during HD was modest due to the partial clearance of bilirubin via HD-enabled diffusion. The only persistent and consistent marker was the post-HD rise in lactate dehydrogenase in association with decreasing haemoglobin. We propose that mechanical stress-induced haemolysis should be considered in children on HD who develop unexplained or persistent anaemia with resistance to increasing doses of iron and erythropoiesis-stimulating agent supplementation.

COVID-19: experiences of lockdown and support needs in children and young adults with kidney conditions.

BACKGROUND: During the initial COVID-19 pandemic, young United Kingdom (UK) kidney patients underwent lockdown and those with increased vulnerabilities socially isolated or 'shielded' at home. The experiences, information needs, decision-making and support needs of children and young adult (CYA) patients or their parents during this period is not well known. METHODS: A UK-wide online survey co-produced with patients was conducted in May 2020 amongst CYA aged 12-30, or parents of children aged < 18 years with any long-term kidney condition. Participants answered qualitative open text alongside quantitative closed questions. Thematic content analysis using a three-stage coding process was conducted. RESULTS: One-hundred and eighteen CYA (median age 21) and 197 parents of children (median age 10) responded. Predominant concerns from CYA were heightened vigilance about viral (68%) and kidney symptoms (77%) and detrimental impact on education or work opportunities (70%). Parents feared the virus more than CYA (71% vs. 40%), and had concerns that their child would catch the virus from them (64%) and would have an adverse impact on other children at home (65%). CYA thematic analysis revealed strong belief of becoming seriously ill if they contracted COVID-19; lost educational opportunities, socialisation and career development; and frustration with the public for not following social distancing rules. Positive outcomes included improved family relationships and community cohesion. Only a minority (14-21% CYA and 20-31% parents, merged questions) desired more support. Subgroup analysis identified greater negative psychological impact in the shielded group. CONCLUSIONS: This survey demonstrates substantial concern and need for accurate tailored advice for CYA based on individualised risks to improve shared decision making.

Bilateral native nephrectomies for severe hypertension in children with stage 5 chronic kidney disease leads to improved BP control following transplantation.

BACKGROUND: Hypertension is a common problem in stage 5 chronic kidney disease (CKD 5) and following kidney transplantation (KT). There is limited data on the outcome of children with CKD 5 who undergo bilateral native nephrectomies (BNN) for the management of hypertension. METHOD: Retrospective review of 134 children who underwent KT at a single centre over a 10-year period and had a minimum follow up period of 1 year. Children who had undergone BNN for hypertension prior to, and after, KT were identified and their outcome with regard to blood pressure (BP), anti-hypertensive medications and graft function was compared with that of the rest of the cohort. RESULTS: Eleven children (8.2%) underwent BNN, including 2 performed after KT, due to poorly controlled BP despite a median of 3 anti-hypertensive medications. The median age at BNN was 7 years (range 0.5-17 years). All 9 children who underwent BNN prior to KT discontinued anti-hypertensive medication after a median of 6 months and remained normotensive post KT. After a median follow up of 5 years following KT, there was a trend towards lower prevalence of hypertension in children who underwent BNN compared with that of the rest of the cohort (9.1% vs 25%, p 0.23). None of the children who underwent BNN had any evidence of proteinuria, and the median eGFR was 74 ml/min/1.73 m 2 after KT. CONCLUSION: BNN for severe hypertension in CKD 5 is associated with resolution of hypertension prior to KT. It is also associated with a trend towards lower prevalence of hypertension and good graft function following KT.

A Sphingosine-1-Phosphate Lyase Mutation Associated With Congenital Nephrotic Syndrome and Multiple Endocrinopathy.

Background: Loss of function mutations in SGPL1 are associated with Sphingosine-1-phosphate lyase insufficiency syndrome, comprising steroid resistant nephrotic syndrome, and primary adrenal insufficiency (PAI) in the majority of cases. SGPL1 encodes sphingosine-1-phosphate lyase (SGPL1) which is a major modulator of sphingolipid signaling. Case Presentation: A Pakistani male infant presented at 5 months of age with failure to thrive, nephrotic syndrome, primary adrenal insufficiency, hypothyroidism, and hypogonadism. Other systemic manifestations included persistent lymphopenia, ichthyosis, and motor developmental delay. Aged 9 months, he progressed rapidly into end stage oligo-anuric renal failure and subsequently died. Sanger sequencing of the entire coding region of SGPL1 revealed the novel association of a rare homozygous mutation (chr10:72619152, c.511A>G, p.N171D; MAF-1.701e-05) with the condition. Protein expression of the p.N171D mutant was markedly reduced compared to SGPL1 wild type when overexpressed in an SGPL1 knockout cell line, and associated with a severe clinical phenotype. Conclusions: The case further highlights the emerging phenotype of patients with loss-of-function SGPL1 mutations. Whilst nephrotic syndrome is a recognized feature of other disorders of sphingolipid metabolism, sphingosine-1-phosphate lyase insufficiency syndrome is unique amongst the sphingolipidoses in presenting with multiple endocrinopathies. Given the multi-systemic and progressive nature of this form of PAI/ nephrotic syndrome, a genetic diagnosis is crucial for optimal management and appropriate screening for comorbidities in these patients.

Pre-emptive rituximab and plasma exchange does not prevent disease recurrence following living donor renal transplantation in high-risk idiopathic SRNS.

BACKGROUND: Children with non-genetic steroid-resistant nephrotic syndrome (SRNS) are at high risk of disease recurrence (DR) and graft loss following renal transplant (RT). Although pre-emptive plasma exchange (PE) and rituximab have been suggested to prevent DR, there is insufficient published data to support this practice. The aim is to study the role of pre-emptive PE and rituximab in the prevention of DR in children with non-genetic SRNS undergoing living donor (LD) RT. METHODS: Prospective single-centre study of four consecutive children (age 6-17 years) with non-genetic SRNS (including two with previous graft loss due to DR) who underwent LD RT between July 2014 and September 2016. All patients received a single dose of rituximab 375 mg/m2 2-4 weeks prior to the RT and four sessions of PE in the week prior to RT. All patients had previously undergone bilateral native nephrectomies. RESULTS: All children had early DR (2-26 days) following LD RT. Following early initiation of PE, three children achieved partial remission (PR) or complete remission (CR) 5-22 days after commencing treatment. One child continued to have heavy proteinuria along with graft dysfunction despite 52 sessions of PE and lost the graft 5 months after RT. At the latest follow-up of 36-60 months following RT, one child remains in CR and two are in PR. The latest eGFR was 45-104 ml/min/1.73m2. CONCLUSIONS: Pre-emptive rituximab and PE does not prevent DR in high-risk non-genetic SRNS. Prompt initiation of PE following DR appears to achieve PR or CR in the majority of patients.

LDL-apheresis-induced remission of focal segmental glomerulosclerosis recurrence in pediatric renal transplant recipients.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) in pediatric patients is typically difficult to treat and will progress to end-stage renal disease (ESRD) in about 10% of cases. Following kidney transplantation, FSGS can recur in up to 56% of renal allografts-with a near 100% recurrence in subsequent transplants. METHODS: Four different pediatric centers across the USA and the UK employed a protocol using LDL-apheresis (LDL-A) and pulse solumedrol to treat recurrent FSGS after transplantation in seven patients. All the patients included in this series demonstrated immediate, or early, recurrence of FSGS, which clinically presented as nephrotic-range proteinuria within hours to days after implantation of the kidney. RESULTS: All patients experienced reductions in urinary protein to creatinine ratios resulting in partial or complete remission. All patients demonstrated improvements in their estimated GFRs at their most recent follow-up since LDL-A discontinuation. CONCLUSIONS: This case series describes the successful treatment, across four different pediatric centers, of seven pediatric patients with recurrent post-transplant FSGS using the Liposorber® LA-15 in combination with pulse solumedrol.

Prostate Cancer Pulmonary Metastasis Presenting as a Ground-Glass Pulmonary Nodule on 68Ga-PSMA-11 PET/CT.

Ga-prostate-specific membrane antigen 11 (PSMA) PET/CT imaging accurately depicts metastatic prostate adenocarcinoma (PCa). Pulmonary metastases of PCa are often overlooked on follow-up imaging in patients after initial treatment and following androgen deprivation therapy. Here we present a rare case of biopsy-proven PCa pulmonary metastasis with a ground-glass appearance. The increased PSMA expression and the evolving CT features of the solid component of the ground-glass nodule detected by PSMA PET/CT imaging led to surgical resection and PET/CT-guided therapy.

Trace element and vitamin concentrations in paediatric dialysis patients.

BACKGROUND: There are few recent data regarding blood micronutrient concentrations and supplementation in children on maintenance dialysis. We investigated micronutrient concentrations following dialysis commencement. METHODS: Retrospective review, including all children on maintenance dialysis (peritoneal dialysis, PD; intermittent haemodialysis, IHD), for nutritional blood concentrations measured over the first 12 months. Patients received pyridoxine and Dialyvit® daily with planned 3-monthly micronutrient concentration monitoring including selenium, manganese, copper, zinc, folate and vitamins A, D, B12 and E. RESULTS: We reviewed 47 children (24 girls) including 19 PD and 28 IHD, median age (IQR) 11.4 (2.8,14.4) years. 33 were white, 5 Asian, 5 black and 4 of other ethnic origins. Vitamin A, B12 and E concentrations were within range in 6%, 20% and 13% respectively, with all others above normal range. Serum folate and vitamin D concentrations were within the desired range of 55%, with the rest above or below target. For trace elements, 37%, 60%, 65% and 89% achieved normal ranges for zinc, manganese, copper and selenium respectively. Deficiencies were seen for zinc (43%), copper (28%), folate (6%) and selenium (4%), whereas 7%, 7%, 20% and 40% had copper, selenium, zinc and manganese levels above normal ranges. Despite standard pyridoxine supplementation, only 6 children were monitored during the study period. CONCLUSIONS: Concentrations of several trace elements and vitamins were outside reference ranges. Response to systematic monitoring and targeted supplementation should be evaluated in future studies. Paediatric dialysis centres should consider undertaking routine nutritional bloods monitoring, particularly for vitamin D, zinc and copper.

Evaluation of the 'Live Life Better Service', a community-based weight management service, for morbidly obese patients.

BACKGROUND: There is a limited evidence on the effectiveness of lifestyle interventions in achieving and maintaining a significant level of weight loss in morbidly obese patients. This study evaluated the impact on weight loss and psychological well-being of a community-based weight management service for morbidly obese patients [body mass index (BMI) ≥35 with related co-morbidities or BMI >40] in Derbyshire county. METHODS: Five hundred and fifty-one participants entered the service since 2010, and 238 participants were still active within the service or had completed the 2-year intervention in April 2013. A one-group pre-post design was used to determine average weight loss (kg) and impact on mental health and well-being [using the validated clinical outcomes of routine evaluation-outcome measure (CORE-OM) questionnaire] among participants. Measurements were recorded at baseline, 12 weeks, 24 weeks, 1 year, 18 months and 2 years, and significance (P ≤ 0.05) was determined using the paired sample t-test. RESULTS: Statistically significant weight loss was recorded at each measurement point for those participants who remained engaged with the service (4.9 kg weight loss at 12 weeks to 18.2 kg at 2 years). There was a significant positive impact on psychological well-being demonstrated by CORE-OM score. CONCLUSIONS: Findings show clinically and statistically significant weight loss among participants with improvements in physical and mental health.

Influenza vaccination for immunocompromised patients: summary of a systematic review and meta-analysis.

Vaccination of immunocompromised patients is recommended in many national guidelines to protect against severe or complicated influenza infection. However, due to uncertainties over the evidence base, implementation is frequently patchy and dependent on individual clinical discretion. We conducted a systematic review and meta-analysis to assess the evidence for influenza vaccination in this patient group. Healthcare databases and grey literature were searched and screened for eligibility. Data extraction and assessments of risk of bias were undertaken in duplicate, and results were synthesised narratively and using meta-analysis where possible. Our data show that whilst the serological response following vaccination of immunocompromised patients is less vigorous than in healthy controls, clinical protection is still meaningful, with only mild variation in adverse events between aetiological groups. Although we encountered significant clinical and statistical heterogeneity in many of our meta-analyses, we advocate that immunocompromised patients should be targeted for influenza vaccination.

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

BACKGROUND: Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events. METHODOLOGY/PRINCIPAL FINDINGS: Electronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I(2) and publication bias was assessed using Begg's funnel plot and Egger's regression test. Many of the 209 eligible studies included an unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR]=0.23; 95% confidence interval [CI]=0.16-0.34; p<0.001) and laboratory confirmed influenza infection (OR=0.15; 95% CI=0.03-0.63; p=0.01) through vaccinating immunocompromised patie nts compared to placebo or unvaccinated controls. We found no difference in the odds of influenza-like illness compared to vaccinated immunocompetent controls. The pooled odds of seroconversion were lower in vaccinated patients compared to immunocompetent controls for seasonal influenza A(H1N1), A(H3N2) and B. A similar trend was identified for seroprotection. Meta-analyses of seroconversion showed higher odds in vaccinated patients compared to placebo or unvaccinated controls, although this reached significance for influenza B only. Publication bias was not detected and narrative synthesis supported our findings. No consistent evidence of safety concerns was identified. CONCLUSIONS/SIGNIFICANCE: Infection prevention and control strategies should recommend vaccinating immunocompromised patients. Potential for bias and confounding and the presence of heterogeneity mean the evidence reviewed is generally weak, although the directions of effects are consistent. Areas for further research are identified.

Probing surface charge potentials of clay basal planes and edges by direct force measurements.

The dispersion and gelation of clay suspensions have major impact on a number of industries, such as ceramic and composite materials processing, paper making, cement production, and consumer product formulation. To fundamentally understand controlling mechanisms of clay dispersion and gelation, it is necessary to study anisotropic surface charge properties and colloidal interactions of clay particles. In this study, a colloidal probe technique was employed to study the interaction forces between a silica probe and clay basal plane/edge surfaces. A muscovite mica was used as a representative of 2:1 phyllosilicate clay minerals. The muscovite basal plane was prepared by cleavage, while the edge surface was obtained by a microtome cutting technique. Direct force measurements demonstrated the anisotropic surface charge properties of the basal plane and edge surface. For the basal plane, the long-range forces were monotonically repulsive within pH 6-10 and the measured forces were pH-independent, thereby confirming that clay basal planes have permanent surface charge from isomorphic substitution of lattice elements. The measured interaction forces were fitted well with the classical DLVO theory. The surface potentials of muscovite basal plane derived from the measured force profiles were in good agreement with those reported in the literature. In the case of edge surfaces, the measured forces were monotonically repulsive at pH 10, decreasing with pH, and changed to be attractive at pH 5.6, strongly suggesting that the charge on the clay edge surfaces is pH-dependent. The measured force profiles could not be reasonably fitted with the classical DLVO theory, even with very small surface potential values, unless the surface roughness was considered. The surface element integration (SEI) method was used to calculate the DLVO forces to account for the surface roughness. The surface potentials of the muscovite edges were derived by fitting the measured force profiles with the surface element integrated DLVO model. The point of zero charge of the muscovite edge surface was estimated to be pH 7-8.