Fifteen-minute consultation: Empowering children, young people and families through shared decision-making: a practical guide.

Shared decision-making (SDM) is a collaborative approach to healthcare decision-making that involves patients and healthcare professionals working together to make decisions that are informed by the best available medical evidence, as well as the patient's values, preferences and goals. The importance of SDM and the intricate interplay among parents, children and young people (CYP), and healthcare professionals are increasingly acknowledged as the crucial aspects of delivering high-quality paediatric care. While there is a substantial evidence base for SDM improving knowledge and reducing decisional conflict, the evidence for long-term measures such as improved health outcomes is limited and mainly inconclusive. To support healthcare teams in implementing SDM, the authors offer a practical guide to enhance decision-making processes and empower CYP and their families.

UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS), commonly caused by focal segmental glomerulosclerosis (FSGS), is associated with progression to stage 5 chronic kidney disease, requirement for kidney replacement therapy and a risk of disease recurrence post-kidney transplantation. Ofatumumab (OFA) is a fully humanised monoclonal antibody to CD20, with similar mechanisms of action to rituximab (RTX). METHODS: We report a case series of seven UK patients (five paediatric, two adult), all of whom developed FSGS recurrence after kidney transplantation and received OFA as part of their therapeutic intervention. All also received concomitant plasmapheresis. The 2-year outcome of these seven patients is reported, describing clinical course, kidney function and proteinuria. RESULTS: Four patients (all paediatric) achieved complete urinary remission with minimal proteinuria 12 months post-treatment. Three of those four also had normal graft function. Two patients showed partial remission-brief improvement to non-nephrotic proteinuria (197 mg/mmol) in one patient, maintained improvement in kidney function (estimated glomerular filtration rate 76 ml/min/1.73 m2) in the other. One patient did not demonstrate any response. CONCLUSIONS: OFA may represent a useful addition to therapeutic options in the management of FSGS recurrence post-transplantation, including where RTX has shown no benefit. Concomitant plasmapheresis in all patients prevents any definitive conclusion that OFA was the beneficial intervention.

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.

Clinical practice guideline management of blood borne viruses within the haemodialysis unit.

Some people who are receiving dialysis treatment have virus infection such as hepatitis B, hepatitis C and/or HIV that is present in their blood. These infections can be transmitted to other patients if blood is contaminated by the blood of another with a viral infection. Haemodialysis is performed by passing blood from a patient through a dialysis machine, and multiple patients receive dialysis within a dialysis unit. Therefore, there is a risk that these viruses may be transmitted around the dialysis session. This documents sets out recommendations for minimising this risk.There are sections describing how machines and equipment should be cleaned between patients. There are also recommendations for dialysing patients with hepatitis B away from patients who do not have hepatitis B. Patients should be immunised against hepatitis B, ideally before starting dialysis if this is possible. There are guidelines on how and when to do this, for checking whether immunisation is effective, and for administering booster doses of vaccine. Finally there is a section on the measures that should be taken if a patient receiving dialysis is identified as having a new infection of hepatitis B, hepatitis C or HIV.

Renal Association Clinical Practice Guideline on Haemodialysis.

This guideline is written primarily for doctors and nurses working in dialysis units and related areas of medicine in the UK, and is an update of a previous version written in 2009. It aims to provide guidance on how to look after patients and how to run dialysis units, and provides standards which units should in general aim to achieve. We would not advise patients to interpret the guideline as a rulebook, but perhaps to answer the question: "what does good quality haemodialysis look like?"The guideline is split into sections: each begins with a few statements which are graded by strength (1 is a firm recommendation, 2 is more like a sensible suggestion), and the type of research available to back up the statement, ranging from A (good quality trials so we are pretty sure this is right) to D (more like the opinion of experts than known for sure). After the statements there is a short summary explaining why we think this, often including a discussion of some of the most helpful research. There is then a list of the most important medical articles so that you can read further if you want to - most of this is freely available online, at least in summary form.A few notes on the individual sections: 1. This section is about how much dialysis a patient should have. The effectiveness of dialysis varies between patients because of differences in body size and age etc., so different people need different amounts, and this section gives guidance on what defines "enough" dialysis and how to make sure each person is getting that. Quite a bit of this section is very technical, for example, the term "eKt/V" is often used: this is a calculation based on blood tests before and after dialysis, which measures the effectiveness of a single dialysis session in a particular patient. 2. This section deals with "non-standard" dialysis, which basically means anything other than 3 times per week. For example, a few people need 4 or more sessions per week to keep healthy, and some people are fine with only 2 sessions per week - this is usually people who are older, or those who have only just started dialysis. Special considerations for children and pregnant patients are also covered here. 3. This section deals with membranes (the type of "filter" used in the dialysis machine) and "HDF" (haemodiafiltration) which is a more complex kind of dialysis which some doctors think is better. Studies are still being done, but at the moment we think it's as good as but not better than regular dialysis. 4. This section deals with fluid removal during dialysis sessions: how to remove enough fluid without causing cramps and low blood pressure. Amongst other recommendations we advise close collaboration with patients over this. 5. This section deals with dialysate, which is the fluid used to "pull" toxins out of the blood (it is sometimes called the "bath"). The level of things like potassium in the dialysate is important, otherwise too much or too little may be removed. There is a section on dialysate buffer (bicarbonate) and also a section on phosphate, which occasionally needs to be added into the dialysate. 6. This section is about anticoagulation (blood thinning) which is needed to stop the circuit from clotting, but sometimes causes side effects. 7. This section is about certain safety aspects of dialysis, not seeking to replace well-established local protocols, but focussing on just a few where we thought some national-level guidance would be useful. 8. This section draws together a few aspects of dialysis which don't easily fit elsewhere, and which impact on how dialysis feels to patients, rather than the medical outcome, though of course these are linked. This is where home haemodialysis and exercise are covered. There is an appendix at the end which covers a few aspects in more detail, especially the mathematical ideas. Several aspects of dialysis are not included in this guideline since they are covered elsewhere, often because they are aspects which affect non-dialysis patients too. This includes: anaemia, calcium and bone health, high blood pressure, nutrition, infection control, vascular access, transplant planning, and when dialysis should be started.

Validating the use of bioimpedance spectroscopy for assessment of fluid status in children.

BACKGROUND: Bioimpedance spectroscopy (BIS) with a whole-body model to distinguish excess fluid from major body tissue hydration can provide objective assessment of fluid status. BIS is integrated into the Body Composition Monitor (BCM) and is validated in adults, but not children. This study aimed to (1) assess agreement between BCM-measured total body water (TBW) and a gold standard technique in healthy children, (2) compare TBW_BCM with TBW from Urea Kinetic Modelling (UKM) in haemodialysis children and (3) investigate systematic deviation from zero in measured excess fluid in healthy children across paediatric age range. METHODS: TBW_BCM and excess fluid was determined from standard wrist-to-ankle BCM measurement. TBW_D2O was determined from deuterium concentration decline in serial urine samples over 5 days in healthy children. UKM was used to measure body water in children receiving haemodialysis. Agreement between methods was analysed using paired t test and Bland-Altman method comparison. RESULTS: In 61 healthy children (6-14 years, 32 male), mean TBW_BCM and TBW_D2O were 21.1 ± 5.6 and 20.5 ± 5.8 L respectively. There was good agreement between TBW_BCM and TBW_D2O (R2 = 0.97). In six haemodialysis children (4-13 years, 4 male), 45 concomitant measurements over 8 months showed good TBW_BCM and TBW_UKM agreement (mean difference - 0.4 L, 2SD = ± 3.0 L). In 634 healthy children (2-17 years, 300 male), BCM-measured overhydration was - 0.1 ± 0.7 L (10-90th percentile - 0.8 to + 0.6 L). There was no correlation between age and OH (p = 0.28). CONCLUSIONS: These results suggest BCM can be used in children as young as 2 years to measure normally hydrated weight and assess fluid status.

The incidence of pediatric acute kidney injury is increased when identified by a change in a creatinine-based electronic alert.

A prospective national cohort study was undertaken to collect data on all cases of pediatric (under 18 yrs of age) acute kidney injury (AKI) identified by a biochemistry-based electronic alert using the Welsh National electronic AKI reporting system. Herein we describe the utility and limitation of using this modification of the KDIGO creatinine-based system data set to characterize pediatric AKI. Of 1,343 incident episodes over a 30-month period, 34.5% occurred in neonates of which 83.8% were AKI stage 1. Neonatal 30-day mortality was 4.1%, with 73.3% of this being accounted for by patients treated in an Intensive Care Unit. In the non-neonatal group, 76.1% were AKI stage 1. Hospital-acquired AKI accounted for 40.1% of episodes while community-acquired AKI represented 29.4% of cases within which 33.9% were admitted to hospital and 30.5% of cases were unclassified. Non-neonatal 30-day mortality was 1.2%, with half of this accounted for by patients treated in the Intensive Care Unit. Nonrecovery of renal function at 30 days occurred in 28% and was significantly higher in patients not admitted to hospital (45% vs. 20%). The reported incidence of AKI in children was far greater than previously reported in studies reliant on clinical identification of adult AKI or hospital coding data. Mortality was highest in neonates and driven by those in the Intensive Care Unit. Nonrecovery of renal function and persistent renal impairment was more common in non-neonates and was especially high in patients with community-acquired AKI who were not hospitalized.

Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland.

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 Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange-treated patients was not adopted due to concerns over treatment-associated complications. Without immunosuppression, the relapse rate was high (five of seven). However, reintroduction of treatment resulted in recovery of renal function. All patients treated with eculizumab achieved sustained remission. Five patients received renal transplants without specific factor H autoantibody-targeted treatment with recurrence in one who also had a functionally significant CFI mutation. Thus, our current practice is to initiate eculizumab therapy for treatment of factor H autoantibody-mediated atypical hemolytic uremic syndrome rather than plasma exchange with or without immunosuppression. Based on this retrospective analysis we see no suggestion of inferior treatment, albeit the strength of our conclusions is limited by the small sample size.

Positive trends in paediatric renal biopsy service provision in the UK: a national survey and re-audit of paediatric renal biopsy practice.

BACKGROUND: Paediatric renal biopsy standards introduced in the UK in 2010 were intended to reduce variation and improve practice. A concurrent national drive was aimed at building robust paediatric nephrology networks to ensure services cater for the needs of the family and minimise time away from home. We aimed to identify current national practice since these changes on behalf of the British Association for Paediatric Nephrology. METHODS: All UK paediatric nephrology centres were invited to complete a survey of their biopsy practice, including advance preparation. From 1 January to 30 June 2012, a national prospective audit of renal biopsies was undertaken at participating centres comparing practice with the British Association for Paediatric Nephrology (BAPN) standards and audit results from 2005. RESULTS: Survey results from 11 centres demonstrated increased use of pre-procedure information leaflets (63.6 % vs 45.5 %, P = 0.39) and play preparation (90.9 % vs 9.1 %, P = 0.0001). Audit of 331 biopsies showed a move towards day-case procedures (49.5 % vs 32.9 %, P = 0.17) and reduced major complications (4.5 % vs 10.4 %, P = 0.002). Biopsies with 18-gauge needles had significantly higher mean pass rates (3.2 vs 2.3, P = 0.0008) and major complications (15.3 % vs 3.3 %, P = 0.0015) compared with 16-gauge needles. CONCLUSIONS: Percutaneous renal biopsy remains a safe procedure in children, thus improving family-centered service provision in the UK.

Dyslipidaemia in children on renal replacement therapy.

BACKGROUND: Information on lipid abnormalities in end-stage renal disease (ESRD) mainly originates from adult patients and small paediatric studies. We describe the prevalence of dyslipidaemia, and potential determinants associated with lipid measures in a large cohort of paediatric ESRD patients. METHODS: In the ESPN/ERA-EDTA registry, lipid measurements were available for 976 patients aged 2-17 years from 19 different countries from the year 2000 onwards. Dyslipidaemia was defined as triglycerides >100 mg/dL (2-9 years) or >130 mg/dL (9-17 years), high-density lipoprotein (HDL) cholesterol <40 mg/dL or non-HDL cholesterol >145 mg/dL. Missing data were supplemented using multiple imputation. RESULTS: The prevalence of dyslipidaemia was 85.1% in peritoneal dialysis (PD) patients, 76.1% in haemodialysis (HD) patients and 55.5% among renal allograft recipients. Both low and high body mass index (BMI) were associated with a less favourable lipid profile. Younger age was associated with a worse lipid profile among PD patients. HDL levels significantly improved after transplantation, whereas no significant improvements were found for triglyceride and non-HDL levels. In transplant recipients, use of cyclosporin was associated with significantly higher non-HDL and HDL levels than tacrolimus usage (P < 0.01). In transplant patients with eGFR < 29 mL/min/1.73 m(2), the mean triglyceride level was 137 mg/dL (99% confidence interval (CI): 119-159) compared with 102 mg/dL among those with eGFR > 90 mL/min/1.73 m(2) (P < 0.0001). CONCLUSIONS: Dyslipidaemia is common among paediatric ESRD patients in Europe. Young age and PD treatment are associated with worse lipid profiles. Although lipid levels generally improve after transplantation, dyslipidaemia may persist due to decreased graft function, high BMI or to the use of certain immunosuppressants.

A Case of Paediatric Anti-Glomerular Basement Membrane Disease Associated with Thrombotic Thrombocytopenic Purpura.

Anti-GBM disease is a rare vasculitis that causes rapid progressive glomerulonephritis and pulmonary haemorrhage. It is usually an adult diagnosis with isolated paediatric cases reported. Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy mainly affecting adults that causes multiorgan ischaemia, microangiopathic haemolytic anaemia, and thrombocytopenia. We present the first paediatric case of concurrent anti-GBM disease and TTP. A 14-year-old boy presented with acute kidney failure and severe pulmonary haemorrhage due to anti-GBM disease, confirmed on auto-antibody testing. There was thrombocytopenia and moderately low ADAMTS13 activity suggestive of TTP. The renal prognosis was poor with a need for dialysis. He was severely unwell with pulmonary haemorrhages requiring the use of extracorporeal membrane oxygenation (ECMO). His disease was treated with corticosteroids, plasma exchange (PEX), rituximab, and cyclophosphamide, resulting in remission. Anti-GBM disease is rare in children but should be considered in those presenting with acute kidney injury, particularly where there has been exposure to pulmonary irritants. An aggressive presentation warrants aggressive treatment with methylprednisolone, PEX, and cyclophosphamide. Rituximab may benefit patients that have concurrent TTP. TTP may exacerbate pulmonary disease, but complete respiratory recovery is possible. Disease relapse is rare in the paediatric age group, and these patients are candidates for kidney transplantation.

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.

Bilateral progressive cystic nephroma in a 9-month-old male infant requiring renal replacement therapy.

We report the case of a 3-year-old boy who presented at 9 months of age with abdominal distension and was found to have a triad of bilateral cystic nephroma, pleuropulmonary blastoma (PPB) and juvenile intestinal polyps. There have been three previous reported cases of patients with the same associated diagnoses. Our patient is the first reported patient with PPB who received renal replacement therapy and progressed to successful renal transplantation. The potential increased risk of progression of malignancy of PPB (type 1) with immunosuppression following transplantation remains unknown.

A systematic review of the accuracy and utility of early markers of Ifosfamide-induced proximal tubulopathy in survivors of childhood cancers.

This study was conducted to identify and assess the accuracy and utility of any early markers of clinically significant proximal tubulopathy in children treated with ifosfamide chemotherapy. Ifosfamide is widely used either as a solitary agent or in conjunction with various other chemotherapeutic agents in treating solid tumors of childhood. It is highly effective but can cause short-term and long-term damage to kidneys, most commonly resulting in a tubular nephropathy and/or glomerular dysfunction. This may lead to chronic renal failure and metabolic bone disease in long-term survivors of childhood cancer. Multiple electronic databases (Cochrane, MEDLINE, EMBASE) were searched for primary studies describing the predictive value of early blood or urine tests to predict proximal tubulopathy. Citation searching (using reference lists and Science Citation Index searches) was also undertaken. Analysis was undertaken using criteria suggested by the MOOSE (Meta-analysis of Observational Studies in Epidemiology) collaboration. Studies were reviewed by at least 2 authors and disagreements resolved by consensus. Initial searches revealed approximately 310 studies of which 38 papers were selected for full analysis. Only 4 papers described the predictive value of early markers proximal tubular nephropathy. The remaining studies estimated prevalence of acute or chronic nephropathy without presenting predictive data. Of the 4 papers selected for analysis, 2 papers assessed the value of beta-2 microglobulinuria, and 3 addressed quantitative aminoaciduria. Test characteristics ranged from sensitivities of 82 to 100% and specificities of 84 to 100%, although the confidence intervals around these estimates were wide. Given the paucity of data, to consider further the use of early markers of proximal tubular nephropathy a prospective evaluation of patients who have been treated with ifosfamide based regimes should be undertaken.

Aminoaciduria in the prediction of ifosfamide-induced tubulopathy after childhood cancer: a feasibility study.

BACKGROUND: Ifosfamide, an alkylating agent used widely in the treatment of childhood malignancy, can cause many side effects including a proximal tubulopathy. Studies suggest that aminoaciduria is seen most commonly of all the biochemical abnormalities of ifosfamide-induced tubulopathy. A recent systematic review has found a paucity of data regarding the value of early markers indicating clinically significant tubulopathy. We undertook a pilot study to determine the feasibility of examining whether patients can be risk-stratified on the basis of aminoaciduria for the development of future significant ifosfamide-induced tubulopathy, to allow the evolution of appropriate follow-up strategies. We also aimed to define accrual rates, costs and clinical demands for a future larger study. METHODS: This observational study recruited 21 patients from the Leeds Paediatric Oncology service. The medical notes of each patient were reviewed for demographic and clinical data. Simultaneous samples of blood and urine were obtained. RESULTS: The investigations in the feasibility study were acceptable to patients and were minimally demanding on both clinical and laboratory staff. Financially, the cost per patient was minimal. This study was not powered to detect significant associations with TmP/GFR (ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate), growth and electrolyte supplementation. However, all patients with minimal aminoaciduria (≤2 elevated urinary amino acids) had normal TmP/GFR and no need for electrolyte supplementation. CONCLUSIONS: This pilot study has shown that a larger study is feasible and may provide clinically useful data to change current practice. This should aim to establish whether the number of abnormal amino acids or the degree of abnormality is most significant in predicting clinically significant proximal tubulopathy.

Vascular access survival in children and young adults receiving long-term hemodialysis.

BACKGROUND: The delivery of long-term hemodialysis therapy in children is complicated by smaller vascular caliber and the potential lifelong requirement for hemodialysis access. Various factors have resulted in the increased use of cuffed central venous catheters (CVLs) in preference to autologous arteriovenous fistulae (AVFs) and arteriovenous synthetic grafts (AVGs). The aim of this study is to compare CVL, AVF, and AVG survival and determine factors affecting their survival. METHODS: A 20-year retrospective study was undertaken of pediatric patients receiving long-term hemodialysis therapy. Age, height, weight, body mass index, and sex were noted at each procedure, in addition to the presence of hypoalbuminemia, underlying diagnosis, type and site of vascular access, and effect of previous access surgery. The grade of operator also was noted. RESULTS: Three hundred four vascular access procedures were performed on 114 patients, with a median age at initial access formation of 12.0 years (range, 4 weeks to 21.9 years). The most common procedure was CVL insertion (182 procedures) and then AVF formation (107 procedures), with only 15 AVGs created. Median censored survival was 3.14 years (95% confidence interval, 1.22 to 5.06) for AVFs and 0.6 years (95% confidence interval, 0.20 to 1.00) for CVLs. Factors adversely affecting vascular access survival were younger age, trainee operator, presence of hypoalbuminemia, and type of access undertaken, with AVF better than CVL. CONCLUSION: This study shows increased survival of AVFs over CVLs and AVGs. Vascular access in children and adolescents may impact on future dialysis accessibility and should be undertaken by those most experienced in each technique.