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Congenital nephrotic syndrome (CNS) is a heterogeneous group of disorders characterized by nephrotic-range proteinuria, hypoalbuminaemia and oedema, which manifest in utero or during the first 3 months of life. The main cause of CNS is genetic defects in podocytes; however, it can also be caused, in rare cases, by congenital infections or maternal allo-immune disease. Management of CNS is very challenging because patients are prone to severe complications, such as haemodynamic compromise, infections, thromboses, impaired growth and kidney failure. In this consensus statement, experts from the European Reference Network for Kidney Diseases (ERKNet) and the European Society for Paediatric Nephrology (ESPN) summarize the current evidence and present recommendations for the management of CNS, including the use of renin–angiotensin system inhibitors, diuretics, anticoagulation and infection prophylaxis. Therapeutic management should be adapted to the clinical severity of the condition with the aim of maintaining intravascular euvolaemia and adequate nutrition, while preventing complications and preserving central and peripheral vessels. We do not recommend performing routine early nephrectomies but suggest that they are considered in patients with severe complications despite optimal conservative treatment, and before transplantation in patients with persisting nephrotic syndrome and/or a WT1-dominant pathogenic variant.Here, experts from the European Reference Network for Kidney Diseases and the European Society for Paediatric Nephrology present recommendations for the management of congenital nephrotic syndrome, including the use of renin–angiotensin system inhibitors, diuretics, anticoagulation and infection prophylaxis.

Background Relapses of nephrotic syndrome are common and are treated with a course of prednisolone (2 mg/kg/day or 60 mg/m 2 /day). This is associated with major adverse effects including diabetes, weight gain, hypertension and behavioural problems. This study is a retrospective review examining the success of treating relapses in steroid-sensitive nephrotic syndrome (SSNS) with low-dose prednisolone and the consequences on subsequent relapse rates. Furthermore, a follow-up study looked at the side-effect profile during treatment with high- versus low-dose prednisolone. Methods Between January 2012 and July 2013, all well children with SSNS presenting with a relapse were advised to start 1 mg/kg prednisolone daily for a maximum of 7 days. In July 2015, we compared the side-effect profile of prednisolone therapy using the parent proxy PedsQL questionnaire for quality of life (QoL). Results Fifty patients were included in the study, with a total of 87 relapses. Sixty-one of the 87 relapses (70 %) responded within a week. Treating relapses with a reduced dose of steroids did not adversely affect the relapse rate in the 6 months preceding and following the current relapse (1.01 vs 0.86, p  = 0.3). Fifteen parents completed the PedsQL questionnaire. Comparison of scores in each category showed significantly higher values in each domain during treatment with low-dose prednisolone compared with high-dose treatment (35.6 vs 18.3, p  < 0.0001; 31.1 vs 15.0, p  < 0.001; 38.3 vs 20.1, p  < 0.0001). Conclusion A low-dose prednisolone regimen was successful in achieving remission in 70 % of relapses of children with SSNS, without adversely affecting the relapse rate. Parent-completed QoL questionnaires showed significantly higher scores on low-dose treatment, indicating better QoL.

Background Steroid-sensitive nephrotic syndrome is the most common form of nephrotic syndrome in childhood, defined by the response to treatment with glucocorticoids with consequent remission. While most children eventually experience spontaneous resolution of the disease, some have a difficult course with frequent relapses or steroid dependence nephrotic syndrome (FRSDNS). The consequent steroid toxicity often prompts administration of other immunosuppressive drugs, traditionally cyclophosphamide. Recently, rituximab has been reported as effective in this disorder, but long-term experience is lacking. Methods Retrospective note review of all children with FRSDNS treated with a first course of cyclophosphamide and/or rituximab in our center between December 2006 and April 2015. We reviewed time to first relapse after treatment, co-medications, and side effects. Results A total of 102 children were treated with cyclophosphamide (79) and/or rituximab (42). Of these, 34 received cyclophosphamide prior to rituximab. Median time to first relapse was 7 months after cyclophosphamide and 14 months after rituximab. Documented side effects of cyclophosphamide included neutropenia, hair loss, and hemorrhagic cystitis (1). Rituximab was associated with an allergic reaction at infusion in two patients. Conclusions Rituximab was used in children with the most difficult to treat FRSDNS, yet was associated with longer remission time and less side effects than cyclophosphamide. A randomized controlled trial is needed to directly compare these drugs.

The findings within this short report, generated from thematic analysis of nine semistructured interviews with the Northern Ireland Project ECHO team (including authors of this reflection) and informed by reflective practice literature,7 highlight important additional lessons for other teams and organisations using the ECHO approach. Participatory approaches to setting curriculum and programme content, and linking objectives to wider service goals such as integration of care, service transformation and achieving measurable patient outcomes, were consistently present in networks that were considered most effective by the Northern Ireland Project ECHO operational team. Participants must feel safe in sharing sensitive information, discussing challenging cases, while being open to learning and critical feedback. Funding This study was undertaken as part of programmatic and process evaluation with healthcare providers funded through the Health and Social Care Board of Northern Ireland.

Background Long-term steroid treatment in children is known to cause obesity and negatively affect growth. The objective of this study was to determine the prevalence of obesity and overweight and analyze linear growth in children with nephrotic syndrome. Methods The study involved 265 children treated with glucocorticoids for nephrotic syndrome for a mean duration of 43 months (range: 6–167, IQR: 17, 63.3). Height, weight, and BMI SDS were recorded at each visit. Rate of change between the final and initial height, weight, and BMI was calculated (Δ score). The cumulative steroid dose (mg/kg/day) during follow-up was calculated. Relapses without significant edema were treated with low-dose steroids and steroid-sparing drugs were used in children with steroid dependency/frequent relapses. Results Mean first BMI SDS was + 1.40 ± 1.30 and final + 0.79 ± 1.30. At initial assessment, 41.4% of the patients were obese (BMI ≥ 95 th percentile) and 19.5% were overweight (BMI 85 th –95 th percentile). At the last clinical visit, 24% were obese and 17% overweight. The children had lower BMI SDS at last clinical visit compared to initial assessment. Mean first height SDS of the cohort was − 0.11 ± 1.22 and final score 0.078 ± 1.14 ( p  < 0.0001). Almost 85% of patients were treated with steroid-sparing drugs. Conclusions Our results indicate that children with nephrotic syndrome, despite a need for steroid treatment for active disease, can improve their obesity and overweight and also improve their linear growth from their first to last visit with us. Graphical abstract

IntroductionIdiopathic nephrotic syndrome is the most common glomerular disease in children. The majority of patients respond well to steroids. However, the relapse rate is high and many develop steroid dependency. Although other immunosuppressive medicines are successfully used as steroid-sparing agents, some children still have frequent relapsing episodes. Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, has shown to be effective in treating difficult frequently relapsing/steroid-dependent nephrotic syndrome (FR/SDNS). Data on the effectiveness and long-term treatment outcomes of repeated courses of RTX are, however, scarce.Material and methodsChildren and young people with FR/SDNS, aged 1–18 years, who received RTX at Great Ormond Street Hospital (GOSH) from 2006 to 2018 were reviewed.ResultsDuring these 12 years, 103 children with FR/SDNS received RTX infusions at GOSH. Among these, 58 cases needed repeated courses of RTX: 2, 3, 4, 5, 6 and 7 repeated courses were given to 21, 21, 7, 5, 1 and 3 patients, respectively. The overall median time to relapse post-RTX was 11 months (range 1–53 months). There was no change in relapse-free interval with subsequent courses of RTX. No difference was found between age groups, genders and ethnicities. No severe side effects were noted.ConclusionsRTX seems to be safe even after several repeated courses. However, long-term follow-up and further studies are needed, with a focus on side-effects in particular.

BackgroundProject ECHO™ (Extension for Community Healthcare Outcomes) is a tele-mentoring programme that uses video-conferencing technology to share evidence-based knowledge, best practice and education by using case-based learning. Hospice UK’s strategic plan is to extend the reach of hospice care (Hospice UK, 2017), with the Project ECHO™ model being identified as vehicle of innovation and a methodology to achieve this. Engagement with hospices throughout the United Kingdom commenced in 2017 and by April 2018, Hospice UK delivered its first three-day training programme ‘Immersion Training’ to two hospices. As of June 2019 a further 15 hospices have completed this training programme in either London or Belfast.The Hospice UK Project Managers for the Project ECHO™ programme, based in London and Belfast, support the operational delivery of the training programme. With additional organisational support from a Programme Management working group, consisting of clinical, finance, ICT, governance, communication and fundraising staff.AimTo examine the experiences and tools used by the Project Managers to deliver the Hospice UK Project ECHO™ Programme.MethodThe Project Managers developed and implemented the following successful tools: Project plan; pre-training support tools/guidelines which hospices use to establish ‘readiness’ to commit to training; operation/programme management guidelines; stakeholder analysis; issue log; fortnightly operational meetings (to map activity against key milestones).ResultsThe Project Managers have established successes and challenges:Success: staff appointed whose sole focus is to manage the Project ECHO™ programme. Engagement with hospices who have thoroughly analysed the ‘strategic fit’ of Project ECHO™ by using the pre–training support tools/guidelines;Challenges: recommended key personnel to include, a champion, a facilitator, an admin/co–ordinator and IT support, who do not attend training.ConclusionsThe Hospice UK Project ECHO™ continues to develop its programme management tools to meet the demands of its customers.

BackgroundPrimary steroid resistant nephrotic syndrome (SRNS) is thought to have either genetic or immune-mediated aetiology. Knowing which children to screen for genetic causes can be difficult. Several studies have described the prevalence of genetic causes of primary SRNS to be between 30 and 40%, but these may reflect a selection bias for genetic testing in children with congenital, infantile, syndromic or familial NS and thus may overestimate the true prevalence in a routine clinical setting.MethodsRetrospective electronic patient record analysis was undertaken of all children with non-syndromic SRNS and presentation beyond the first year of life, followed at our centre between 2005 and 2020.ResultsOf the 49 children who met the inclusion criteria, 5 (10%) had causative variants identified, predominantly in NPHS2. None responded to immunosuppression. Of the 44 (90%) who had no genetic cause identified, 33 (75%) had complete or partial remission after commencing second-line immunosuppression and 67% of these had eGFR > 90 ml/min/1.73 m2 at last clinical follow-up. Of the children who did not respond to immunosuppression, 64% progressed to kidney failure.ConclusionsIn our cohort of children with non-syndromic primary SRNS and presentation beyond the first year of life, we report a prevalence of detectable causative genetic variants of 10%. Those with identified genetic cause were significantly (p = 0.003) less likely to respond to immunosuppression and more likely (p = 0.026) to progress to chronic kidney disease. Understanding the genetics along with response to immunosuppression informs management in this cohort of patients and variant interpretation.A higher resolution version of the Graphical abstract is available as Supplementary information.

BackgroundLevamisole is frequently used as a steroid-sparing agent in children with steroid-sensitive nephrotic syndrome. Side effects, such as neutropenia, gastro-intestinal upset and skin rash, have been reported. We noted an increase in creatinine in some of our patients, but literature on the effect of levamisole on kidney function is lacking.MethodsA retrospective cohort study was conducted, including patients 1–18 years of age, treated for steroid-sensitive nephrotic syndrome with levamisole at Great Ormond Street Hospital for Children between January 2010 and January 2020. Data was collected on clinical observations and serum creatinine values before, during and after treatment. eGFR was calculated using the Schwartz equation.ResultsIn total, 75 children were included in the analysis. The median duration of treatment was 19 (IQR 12–27) months. The median estimated GFR was 134 (IQR 119–160), 101 (IQR 91–113) and 116 (IQR 106–153) ml/min/1.73 m2, respectively, before, during and after treatment with levamisole. The difference between eGFR before and after treatment compared with during treatment was statically significant (P < 0.0001). During the treatment period, the eGFR decrease was not progressive. The median levamisole dose was 2.5 (IQR 2.3–2.6) mg/kg on alternate days, and the dose was not correlated with the decrease in eGFR (r = 0.07, 95% CI − 0.22 to 0.35).ConclusionLevamisole significantly decreases eGFR. However, this decrease is not progressive or irreversible and would not be an indication to discontinue the treatment.

Congenital nephrotic syndrome (CNS) is a heterogeneous group of disorders presenting with massive proteinuria within the first 3 months of life almost inevitably leading to end-stage kidney disease. The Work Group for the European Reference Network for Kidney Diseases (ERKNet) and the European Society for Pediatric Nephrology (ESPN) has developed consensus statement on genetic aspects of CNS diagnosis and management. The presented expert opinion recommends genetic diagnostics as the key diagnostic test to be ordered already during the initial evaluation of the patient, discusses which phenotyping workup should be performed and presents known genotype–phenotype correlations.