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Children with frequently relapsing, steroid-dependent nephrotic syndrome (FRSDNS) often require multiple courses of rituximab. However, long-term effects from repeated treatments remain unknown. In this international, multicenter study of 346 children receiving 1149 courses of rituximab, the risk of relapse decreased and relapse-free survival significantly improved with repeated treatments. Important side effects, including hypogammaglobulinemia, neutropenia, and infections, were mostly mild, but significant adverse events could occur. The incidence of side effects did not increase with more treatment courses nor a higher cumulative dose of rituximab. These findings suggest that repeating rituximab therapy is an effective and reasonably safe approach for most children with FRSDNS.

Trials in children with chronic kidney disease do not consistently report outcomes that are critically important to patients and caregivers. This can diminish the relevance and reliability of evidence for decision making, limiting the implementation of results into practice and policy. As part of the Standardized Outcomes in Nephrology—Children and Adolescents (SONG-Kids) initiative, we convened 2 consensus workshops in San Diego, California (7 patients, 24 caregivers, 43 health professionals) and Melbourne, Australia (7 patients, 23 caregivers, 49 health professionals). This report summarizes the discussions on the identification and implementation of the SONG-Kids core outcomes set. Four themes were identified; survival and life participation are common high priority goals, capturing the whole child and family, ensuring broad relevance across the patient journey, and requiring feasible and valid measures. Stakeholders supported the inclusion of mortality, infection, life participation, and kidney function as the core outcomes domains for children with chronic kidney disease.

Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney disease. Recurrence of FSGS after kidney transplantation significantly increases allograft loss, leading to morbidity and mortality. Currently, there are no consensus guidelines for identifying those patients who are at risk for recurrence or for the management of recurrent FSGS. Our work group performed a literature search on PubMed/Medline, Embase, and Cochrane, and recommendations were proposed and graded for strength of evidence. Of the 614 initially identified studies, 221 were found suitable to formulate consensus guidelines for recurrent FSGS. These guidelines focus on the definition, epidemiology, risk factors, pathogenesis, and management of recurrent FSGS. We conclude that additional studies are required to strengthen the recommendations proposed in this review.

Peritonitis- and catheter-related infections due to nontuberculous mycobacteria (NTM) including Mycobacterium abscessushave been reported among adults on peritoneal dialysis (PD). There is no recommended antimicrobial regimen for the treatment of M. abscessusperitonitis. Clofazimine has emerged as an important adjuvant antimicrobial treatment of M. abscessuslung infection. We report, to our knowledge, the first case of M. abscessusPD peritonitis in a child treated successfully using clofazimine as a novel adjuvant therapy to amikacin and clarithromycin. Her clinical features were similar to those of bacterial peritonitis, but she had persistence of symptoms and high inflammatory markers despite empirical therapy for peritonitis. Bacterial culture of PD effluent became positive for M. abscessusafter 5 days. There was complete symptom resolution after 6 days of multidrug therapy. Due to ototoxicity, amikacin was discontinued after 6 weeks, while clarithromycin and clofazimine were continued for 9 months to ensure complete pathogen eradication before a planned renal transplant. A high index of suspicion in refractory or culture-negative cases is important for the diagnosis of NTM peritonitis. Multidrug therapy is recommended for M. abscessusinfections. Clofazimine was chosen as a novel adjunct antimicrobial because of its pharmacokinetics, ease of administration, cost-effectiveness, and lack of serious adverse events.

Kidney disease is a global public health concern across the age spectrum, including in children. However, our understanding of the true burden of kidney disease in low-resource areas is often hampered by a lack of disease awareness and access to diagnosis. Chronic kidney disease (CKD) in low-resource settings poses multiple challenges, including late diagnosis, the need for ongoing access to care and the frequent unavailability of costly therapies such as dialysis and transplantation. Moreover, children in such settings are at particular risk of acute kidney injury (AKI) owing to preventable and/or reversible causes — many children likely die from potentially reversible kidney disease because they lack access to appropriate care. Acute peritoneal dialysis (PD) is an important low-cost treatment option. Initiatives, such as the Saving Young Lives programme, to train local medical staff from low-resource areas to provide care for AKI, including acute PD, have already saved hundreds of children. Future priorities include capacity building for both educational purposes and to provide further resources for AKI management. As local knowledge and confidence increase, CKD management strategies should also develop. Increased awareness and advocacy at both the local government and international levels will be required to continue to improve the diagnosis and treatment of AKI and CKD in children worldwide.

The inconsistency in outcomes reported and lack of patient-reported outcomes across trials in children with chronic kidney disease (CKD) limits shared decision making. As part of the Standardized Outcomes in Nephrology (SONG)-Kids initiative, we aimed to generate a consensus-based prioritized list of critically important outcomes to be reported in all trials in children with CKD.

Background: Peritoneal dialysis (PD) remains the most widely used modality for chronic dialysis in children, particularly in younger children and in lower and middle income countries (LMICs). We present guidelines for dialysis initiation, modality selection, small solute clearance, and fluid removal in children on PD. A review of the literature and key studies that support these statements are presented.Methods: An extensive Medline search for all publications on PD in children was performed using predefined search criteria.Results: High-quality randomized trials in children are scarce and current clinical practice largely relies on data extrapolated from adult studies or drawn from observational cohort studies in children. The evidence and strength of the recommendation is GRADE-ed, but in the absence of high-quality evidence, the opinion of the authors is provided and must be carefully considered by the treating physician, and adapted to local expertise and individual patient needs as appropriate. We discuss the timing of dialysis initiation, factors to be considered when selecting a dialysis modality, the assessment and management of volume status on PD, achieving optimal small solute clearance, and the importance of preserving residual kidney function. While optimal dialysis must remain the goal for every patient, a careful discussion with fully informed patients and caregivers is important to understand the patient and family’s expectations of dialysis and reasonable adjustments to the dialysis program may be considered in accordance with a philosophy of shared decision-making.Conclusions: There continues to be very poor evidence in the field of chronic PD in children and these recommendations can at best serve to guide clinical decision-making. In LMICs, every effort should be made to conform to the framework of these statements, taking into account resource limitations.

Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology–Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD.

Chronic kidney disease (CKD) has wide-ranging and long-term consequences for young people and their families. The omission of outcomes that are important to young people with CKD and their caregivers limits knowledge to guide shared decision making. We aimed to identify the outcomes that are important to young people with CKD and their caregivers.

There are an estimated 14,000 randomized trials published in chronic kidney disease. The most frequently reported outcomes are biochemical endpoints, rather than clinical and patient-reported outcomes including cardiovascular disease, mortality, and quality of life. While many trials have focused on optimizing kidney health, the heterogeneity and uncertain relevance of outcomes reported across trials may limit their policy and practice impact. The international Standardized Outcomes in Nephrology (SONG) Initiative was formed to identify core outcomes that are critically important to patients and health professionals, to be reported consistently across trials. We convened a SONG Implementation Workshop to discuss the implementation of core outcomes. Eighty-two patients/caregivers and health professionals participated in plenary and breakout discussions. In this report, we summarize the findings of the workshop in two main themes: socializing the concept of core outcomes, and demonstrating feasibility and usability. We outline implementation strategies and pathways to be established through partnership with stakeholders, which may bolster acceptance and reporting of core outcomes in trials, and encourage their use by end-users such as guideline producers and policymakers to help improve patient-important outcomes.

Effective communication and shared decision making improve quality of care and patient outcomes but can be particularly challenging in pediatric chronic disease because children depend on their parents and clinicians to manage complex health care and developmental needs. We aimed to describe the perspectives of children with chronic kidney disease (CKD) and their parents with regard to communication and decision making.

Objective: To study the effect of a Chinese herbal decoction (CM), which contained 21 different herbs, on clinical remission in a patient with lupus nephritis and chronic nephrotic syndrome. Design: Case report describing the clinical and laboratory markers of lupus activity in the patient before and after treatment with CM. We also studied the in vitro effect of CM and its hydrophobic extract on spontaneous IgG production by peripheral blood mononuclear cells (PBMCs) from 12 patients with systemic lupus erythematosus (SLE) compared with 9 healthy control subjects. Results: Spontaneous PBMC IgG production was significantly higher in patients with SLE (mean [+ or -] SD, 20.4 [+ or -] 10.6 X [10.sup.-5] g/L) compared with controls (4.7 [+ or -] 1.9 x [10.sup.-5] g/L) (P [is less than] .001). Addition of CM and its hydrophobic extract to PBMCs from patients with SLE resulted in significant suppression of spontaneous IgG production. Conclusions: The CM may contain some active pharmacological compound with immunosuppressive properties useful in the treatment of SLE. Further controlled studies are important to evaluate the efficacy of this medicine, potential toxic effects, and the possible immunosuppressive mechanisms of the active component(s). Arch Pediatr Adolesc Med. 1999; 153:850-852, A Chinese herbal recipe containing 21 different herbs was used to bring about remission of lupus nephritis and chronic kidney syndrome, which indicates that the Chinese medicine may be useful in the treatment of systemic lupus erythematosus (SLE). The patient was a 16 year old Chinese girl who had first shown signs of SL:E at age seven. After four months of herbal therapy, her edema was gone and her blood pressure was normal. The recipe contained herbs from the genera Prubella, Lycium, Bletilla, Ligustrum, Dianthus, Myrrha, Eucommia, Rehmannia, Rosa, Rubia, Imperata, Curculigo, Panax, Astragalus, Codonopsis, Dioscorea, Nelumbo, Boswellia, Polygonum, Citrus, and Glycyrrhiza

Rare kidney diseases encompass at least 150 different conditions, most of which are inherited. Although individual rare kidney diseases raise specific issues, as a group these rare diseases can have overlapping challenges in diagnosis and treatment. These challenges include small numbers of affected patients, unidentified causes of disease, lack of biomarkers for monitoring disease progression, and need for complex care. To address common clinical and patient issues among rare kidney diseases, the KDIGO Controversies Conference entitled, Common Elements in Rare Kidney Diseases, brought together a panel of multidisciplinary clinical providers and patient advocates to address five central issues for rare kidney diseases. These issues encompassed diagnostic challenges, management of kidney functional decline and progression of chronic kidney disease, challenges in clinical study design, translation of advances in research to clinical care, and provision of practical and integrated patient support. Thus, by a process of consensus, guidance for addressing these challenges was developed and is presented here.

The nutritional status and management of children with CKD are complex and require a combined pediatric nephrology team work approach with physicians, nutritionists, nurses, and physical/occupational therapists. Prospective observational studies such as Children with CKD (CKiD) in the US, the 4C study in Europe and the International Pediatric Peritoneal Dialysis Network (IPPN) have advanced the field. However, most recommendations and guidelines from international task forces such as Kidney Diseases Improving Global Outcomes (KDIGO) and Pediatric Renal Nutrition Taskforce (PRNT) are opinion- rather than evidence-based. There is exciting ongoing research to improve nutrition in children with CKD to help them thrive.

Clinical decision-making priorities may differ among children, their parents, and their clinicians. This study describes clinicians’ perspectives on shared decision making in pediatric chronic kidney disease (CKD) and identifies opportunities to improve shared decision making and care for children with CKD and their families.

Minimal-change nephrotic syndrome (MCNS) has been associated with atopy. As interleukin-13 (IL-13) has been implicated in the pathogenesis of MCNS, we postulated that IL-13 genetic polymorphisms could influence either susceptibility or clinical course of the disease.

Thepotential of higher plants as sources for new immunosuppressive medications is well recognized. In our experiments we investigated the immunosuppressive effect of a highly refined and potent extract of a Chinese herbal preparation, CMX-13, on inhibiting acute allograft rejection (AR) in a highly histoincompatible rat lung transplant model, BN→LEW, and on lymphocyte activation and cytokine gene expression in vitro.

Objectives: To study the efficacy and safety of 1 year of growth hormone (GH) therapy in children with steroid-dependent nephrotic syndrome.

Major histocompatibility complex (MHC) antigen expression on cells is a prerequisite for immune interaction with activated T-cells. This study examined the ability of sera from patients with systemic lupus erythematosus (SLE) to modulate MHC expression on vascular endothelial cells. SLE sera were able to selectively upregulate MHC class I antigen expression on cultured human umbilical venous endothelial (HUVE) cells, without concomitant induction of MHC class II antigen. The stimulation index (SI) for MHC class I expression produced by SLE sera (1.21 ± 0.23) was significantly higher than those for normal controls (1.01 ± 0.10) (P < 0.0001) and non-SLE patients (1.12 ± 0.14) (P < 0.05). Additionally, active SLE patients had higher mean SI than inactive patients (P < 0.001). Preincubation of SLE sera with Protein A-Sepharose beads conjugated with antibodies against tumor necrosis factor-α and interferon-α was able to significantly reduce their ability to upregulate class I MHC expression by HUVE cells, indicating that these cytokines were responsible for the modulatory effect. This could be an important mechanism for the immune-mediated vascular injury seen in SLE. Copyright 1993, 1999 Academic Press

Summary:Various polyspecific autoantibodies have been described in the sera of patients with IgA nephropathy, including anti‐IgG, anti‐IgA, antigalactosyl, antifibronectin and antimesangial antibodies. We and other authors have demonstrated the presence of antivascular endothelial cell (VEC) antibodies, in up to 32% of patients with IgA nephropathy. These antibodies were directed against molecules on the endothelial cell surface. Some of these antibodies were directed against HLA class I antigens; the majority, however, were reactive against antigens present on unstimulated endothelial cells, as prior stimulation of the cells with interferon‐γ or interleukin 1 did not result in an increase in anti‐VEC activity of the sera. The clinical significance of these anti‐VEC antibodies in IgA nephropathy is unknown. A significant correlation was demonstrated between these antibodies and the presence of heavy proteinuria. A significant association was also shown between the presence of these antibodies and the histopathologic markers of activity such as crescents and focal and segmental necrotizing lesions, as well as immunoglobulin and C3 deposition in the vessel walls.

Acute kidney injury continues to be a highly occurring disease in the intensive care unit, specifically affecting up to a third of critically ill neonates as per various studies. Although first-line treatments of acute kidney injury are noninvasive, kidney replacement therapy (KRT) is indicated when conservative management modes fail. There are various modalities of KRT which can be used for neonatal populations, including peritoneal dialysis, hemodialysis, and continuous KRT. However, these KRT modalities present their own challenges in this specific patient population Thus, it is the aim of this review to introduce each of these KRT modalities in terms of their challenges, advances, and future directions, with specific emphasis on new technology including the Cardio-Renal Pediatric Emergency Dialysis Machine, Newcastle infant dialysis and ultrafiltration system, and the Aquadex system for ultrafiltration.

This report describes the clinical features of H1N1 2009 influenza infection in 10 young renal patients receiving chronic dialysis or immunosuppressants, and to compare their durations of viral shedding with 20 healthy controls. Although patients shed the virus for longer periods compared with controls, all had a self-limited clinical course. Studies on indications, dosages and durations of antiviral therapy in renal and immunocompromised patients are warranted.

We report on 3 immunocompromised children infected with pandemic influenza A/H1N1/2009 in whom mixtures of oseltamivir-susceptible and oseltamivir-resistant viral populations developed, despite them receiving relatively short-term courses of oseltamivir. In addition, it was found that bacterial coinfections were common, indicating that empiric, antibiotics should be considered in such patients when infected with influenza virus.

This study compared the pattern of acute glomerulonephritis (AGN), a disease known to be influenced by socioeconomic and environmental factors, in children 12 years and under, for the years 1971 and 1985. All children admitted to the four major paediatric departments with haematuria and at least two of the following (oedema, hypertension or oliguria) had an initial diagnosis of AGN. A sample population from one unit from 1980 to 1984 showed that over 70% of these children had evidence of a post-streptococcal aetiology. In 1971, 411 children were admitted with AGN, as compared with only 58 in 1985. The age-sex-race standardized rates for 1971 and 1985 were 0.632 and 0.023/1,000 children 12 years and under, respectively (P<0.001). The mean age of presentation was lower in 1971. Over this period, Singapore saw a threefold rise in the gross national product, accompanied by rapid urbanization. On analysis of the housing pattern, only 31% of the children lived in high-rise apartments in 1971, in contrast with 86% in 1985 (P<0.001). The majority of non-apartment dwellers had homes in runal districts. From an epidemiological perspective, factors which could have led to the highly significant decline in prevalence of AGN in Singapore children included improvement in the socioeconomic status and health care system, and urbanization of the country.

ABSTRACTAn immunocompromised child with influenza A/H3N2 virus infection, treated with oseltamivir from day 1, had nasal swabs taken on days 1, 4, 7, and 10 of the illness. Pyrosequencing showed increasing proportions of viruses with R292K (neuraminidase gene) and G186D (hemagglutinin gene) mutations, resulting in a viral load rebound by day 10.