BACKGROUND: Approximately 40% of children with diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), which increases the risk of chronic kidney damage. At present, there is limited knowledge of racial or ethnic differences in diabetes-related kidney injury in children with diabetes. Understanding whether such differences exist will provide a foundation for addressing disparities in diabetes care that may continue into adulthood. Further, it is currently unclear which children are at risk to develop worsening or sustained DKA-related AKI. The primary aim is to determine whether race and ethnicity are associated with DKA-related AKI. The secondary aim is to determine factors associated with sustained AKI in children with DKA.
METHODS: This retrospective, multicentre, cross-sectional study of children with type 1 or type 2 diabetes with DKA will be conducted through the Paediatric Emergency Medicine Collaborative Research Committee. Children aged 2-18 years who were treated in a participating emergency department between 1 January 2020 and 31 December 2023 will be included. Children with non-ketotic hyperglycaemic-hyperosmolar state or who were transferred from an outside facility will be excluded. The relevant predictor is race and ethnicity. The primary outcome is the presence of AKI, defined by Kidney Disease: Improving Global Outcomes criteria. The secondary outcome is \'sustained\' AKI, defined as having AKI ≥48 hours, unresolved AKI at last creatinine measurement or need for renal replacement therapy. Statistical inference of the associations between predictors (ie, race and ethnicity) and outcomes (ie, AKI and sustained AKI) will use random effects regression models, accounting for hospital variation and clustering.
BACKGROUND: The Institutional Review Board of Children\'s Minnesota approved this study. 12 additional sites have obtained institutional review board approval, and all sites will obtain local approval prior to participation. Results will be presented at local or national conferences and for publication in peer-reviewed journals.

BACKGROUND: Kidney transplantation is the preferred therapy for children with stage 5 chronic kidney disease (CKD-5). However, there is a wide variation in access to kidney transplantation across the UK for children. This study aims to explore the psychosocial factors that influence access to and outcomes after kidney transplantation in children in the UK using a mixed-methods prospective longitudinal design.
METHODS: Qualitative data will be collected through semistructured interviews with children affected by CKD-5, their carers and paediatric renal multidisciplinary team. Recruitment for interviews will continue till data saturation. These interviews will inform the choice of existing validated questionnaires, which will be distributed to a larger national cohort of children with pretransplant CKD-5 (n=180) and their carers. Follow-up questionnaires will be sent at protocolised time points regardless of whether they receive a kidney transplant or not. Coexisting health data from hospital, UK renal registry and National Health Service Blood and Transplant registry records will be mapped to each questionnaire time point. An integrative analysis of the mixed qualitative and quantitative data will define psychosocial aspects of care for potential intervention to improve transplant access.
METHODS: Qualitative data will be analysed using thematic analysis. Quantitative data will be analysed using appropriate statistical methods to understand how these factors influence access to transplantation, as well as the distribution of psychosocial factors pretransplantation and post-transplantation.
BACKGROUND: This study protocol has been reviewed by the National Institute for Health Research Academy and approved by the Wales Research Ethics Committee 4 (IRAS number 270493/ref: 20/WA/0285) and the Scotland A Research Ethics Committee (ref: 21/SS/0038). Results from this study will be disseminated across media platforms accessed by affected families, presented at conferences and published in peer-reviewed journals.

Immunoglobulin A nephropathy represents the most prevalent cause of glomerulonephritis worldwide and may lead to renal failure in a relevant number of cases in both paediatric and adult subjects. Although their pathogenesis is still largely unclear, evidence of immune abnormalities provides the background for the use of immunosuppressive drugs, such as corticosteroids, calcineurin inhibitors, and antiproliferative and alkylating agents. Unfortunately, these treatments fail to achieve a sustained remission in a significant percentage of affected patients and are burdened by significant toxicities. Recent developments of new biologics, including anti-BAFF/APRIL inhibitors and molecules targeting complement components, offered the opportunity to selectively target immune cell subsets or activation pathways, leading to more effective and safer hypothesis-driven treatments. However, studies testing new biologic agents in IgAN should also consider paediatric populations to address the unique needs of children and close the therapeutic gap between adult and paediatric care.

BACKGROUND: Alport syndrome (AS) is one of the most common fatal hereditary renal diseases in human, with a high risk of progressing to end-stage renal disease without effective treatments. Mesenchymal stem cells (MSCs) have recently emerged as a promising therapeutic strategy for chronic kidney disease. However, the safety and therapeutic potential of MSC transfusion for patients with AS are still need to be confirmed. Therefore, we have designed a clinical trial to evaluate the hypothesis that intravenous infusion of human umbilical cord-derived MSC (hUC-MSC) is safe, feasible, and well-tolerated in children with AS.
METHODS: We report the protocol of the first prospective, open-label, single-arm clinical trial to evaluate the safety and preliminary efficacy of hUC-MSC transfusion in children with early-stage AS. Paediatric patients diagnosed with AS who have persistent albuminuria will be candidates for screening. Twelve eligible patients are planned to recruit and will receive hUC-MSC infusions under close safety monitoring, and complete the efficacy assessments at scheduled follow-up visits. The primary endpoints include the occurrence of adverse events to assess safety and the albuminuria level for efficacy evaluation. Secondary endpoint assessments are based on haematuria and glomerular filtration measurements. Each patient\'s efficacy endpoints will be evaluated against their baseline levels. Additionally, the underlying mechanism of hUC-MSC therapy will be explored through transcriptomic and proteomic analysis of blood and urine samples.
BACKGROUND: The protocol (V.1.0, date 17 January 2015) was approved by the institutional review board of the Affiliated Taihe Hospital of Hubei University of Medicine (ethical approval 03 March 2015). Written informed consent will be obtained from the patient and/or guardians before study specific process. In addition to publication in a peer-reviewed scientific journal, a lay summary of study will be available for participants and the public on the Chinese Organization for Rare Disorders website (http://www.cord.org.cn/).
BACKGROUND: ISRCTN62094626.

BACKGROUND: Oral health conditions are common in children and young people (CYP) with kidney disorders. There is currently limited literature on how confident paediatric nephrology teams feel to identify and manage oral health concerns for their patients.
METHODS: An exploratory mixed-method survey was distributed across all 13 UK specialist paediatric nephrology centres with responses received from consultants, registrars, specialist nurses and special interest (SPIN) paediatricians.
RESULTS: Responses received from 109 multidisciplinary team members of 13/13 (100%) UK tertiary units. Ninety-two percent (n = 100) of respondents reported they had never received any training in oral health and 87% (n = 95) felt that further training would be beneficial to optimise care for patients and improve communication between medical and dental teams. Most respondents reported that they did not regularly examine, or enquire about, their patients\' oral health. Only 16% (n = 17) reported that all their paediatric kidney transplant recipients underwent routine dental assessment prior to transplant listing. Severe adverse oral health outcomes were rarely reported and only 11% (n = 12) of respondents recalled having a patient who had a kidney transplant delayed or refused due to concerns about oral infection. Seventy-eight percent (n = 85) felt that joint working with a dental team would benefit patients at their unit; however, 17% (n = 18) felt that current infrastructure does not currently support effective joint working.
CONCLUSIONS: Across the UK, paediatric kidney health professionals report lack of confidence and training in oral health. Upskilling subspecialty teams and creating dental referral pathways are recommended to maximise oral health outcomes for CYP with kidney diseases.

BACKGROUND: Although steroid therapy is a standard of care for nephrotic syndrome treatment, 15-20% of patients do not respond to it. Finding the genetic background is possible in >10% of steroid-resistant nephrotic syndrome (SRNS) cases. Variants in genes encoding nuclear pore complex proteins are a novel cause of paediatric steroid-resistant nephrotic syndrome (SRNS). Recent studies suggest NUP93 variants to be a significant cause of paediatric onset SRNS. The clinical data on certain variants and disease history are still very limited.
RESULTS: We report the SRNS case of a 12-year-old boy with two detected NUP93 variants, which are pathogenic and possibly pathogenic. The onset of the disease was early and severe. The patient was admitted to the paediatric nephrology department due to nephrotic-range proteinuria and hypoalbuminemia with a long medical history of steroid and non-steroid immunosuppressive treatment. The genetic panel targeting 50 genes, clinically relevant for nephrotic syndrome, was performed. The only gene which was found to be affected by mutations, namely c.2326C>T and c.1162C>T, respectively, was NUP93. Conclusions: NUP93 variants are rarely identified as causes of SRNS. Clinical data are of utmost importance to establish the standard of care for SRNS patients suffering from this genetic disfunction. This is the first case of a heterozygous patient with the c.2326C>T and c.1162C>T variants and confirmed clinical history of the SRNS described so far. Our data suggest the clinical relevance of the c.1162C>T variant.

UNASSIGNED: The objective of this study was to identify nephrology topics of lowest perceived competency and importance for general paediatricians.
UNASSIGNED: Surveys were distributed to general paediatricians, paediatric residents, paediatric residency program directors, and paediatric nephrologists. Perceived importance and competence were rated on a 5-point Likert scale. Means and 95% confidence intervals were calculated.
UNASSIGNED: Mean perceived competency from general paediatricians across all nephrology domains was 3.0, 95%CI (2.9 to 3.1) and mean importance was 3.2, 95%CI (3.1 to 3.3). Domains scoring below the means for competence and importance, respectively were kidney stones (2.5, 95%CI [2.2 to 2.7]) and 2.6, 95%CI [2.3 to 2.8]), acute kidney injury (2.5, 95%CI [2.2 to 2.8] and 2.4, 95%CI [2.1 to 2.8]), chronic kidney disease (1.9, 95%CI [1.7 to 2.2] and 2.1, 95%CI [1.8 to 2.4]), tubular disorders (1.8, 95%CI [1.6 to 2.0] and 2.0, 95%CI [1.8 to 2.3]), and kidney transplant (1.6, 95%CI [1.4 to 1.8] and 1.7, 95%CI [1.4 to 1.9]). Residents, program directors, and paediatric nephrologists agreed that stones, chronic kidney disease, tubular disorders, and transplant were of lower importance. However, acute kidney injury was the domain with the largest discrepancy in perceived importance between residents (4.4, 95%CI [4.2 to 4.6]), nephrologists (4.2, 95%CI [3.8 to 4.6]), and program directors (4.2, 95%CI [3.7 to 4.7]) compared to general paediatricians ([2.4, 95%CI [2.1 to 2.8]; P<0.05).
UNASSIGNED: Paediatricians did not believe acute kidney injury was important to their practice, despite expert opinion and evidence of long-term consequences. Educational interventions must address deficits in crucial domains of renal health in paediatrics.

Glucocorticoids induce remission in 90% of children with idiopathic nephrotic syndrome (INS). Some become steroid-dependent (SD) and require the addition of steroid sparing drugs such as calcineurin-inhibitors (CNI) or cyclophosphamide, to maintain remission. Considering the toxicity of these drugs, alternative interventions are needed for long-term treatment. The anti-CD20 antibody rituximab has shown promising steroid-sparing properties, with conflicting results in complicated forms of SD-INS. Mycophenolate mofetil (MMF) resulted effective in maintaining free-steroid remission, however, studies are limited to few uncontrolled trials with reported different dose of MMF.
This open-label, two-parallel-arm, superiority controlled randomised clinical trial will enrol children with SD-INS maintained in remission with oral glucocorticoids or CNI. Children and young adults will be randomised to either MMF (1.200 mg/m2) or rituximab (375 mg/m2) infusion. After enrolment, glucocorticoids will be tapered until complete withdrawal. We will enrol 160 children and young adults to detect as significant at the two-sided p value of 0.01 with a power >0.8 a reduction in the risk of 1-year relapse (primary end-point). As secondary endpoints, we will compare the amount of glucocorticoids required to maintain complete remission at 6 and 24 months.
The trial was approved by the local ethics boards (Comitato Etico Regione Liguria CER Liguria https://www.portalericerca-liguria.it/). We will publish the study results at international scientific meetings.
NCT004585152.

Preeclampsia is a protean syndrome causing a kidney disease characterised by hypertension and proteinuria, usually considered transitory and reversible after delivery. Its prevalence ranges from 3-5 to 10% if all the related disorders are considered. This narrative review, on behalf of the Kidney and Pregnancy Study Group of the Italian Society of Nephrology, focuses on three reasons why preeclampsia should concern paediatric nephrologists and how they can play an important role in its prevention, as well as in the prevention of future kidney and cardiovascular diseases. Firstly, all diseases of the kidney and urinary tract diagnosed in paediatric age are associated with a higher risk of adverse pregnancy-related outcomes, including preeclampsia. Secondly, babies with low birth weights (small for gestational age, born preterm, or both) have an increased risk of developing the full panoply of metabolic diseases (obesity, hypertension, early-onset cardiopathy and chronic kidney disease) and girls are at higher risk of developing preeclampsia when pregnant. The risk may be particularly high in cases of maternal preeclampsia, highlighting a familial aggregation of this condition. Thirdly, pregnant teenagers have a higher risk of developing preeclampsia and the hypertensive disorders of pregnancy, and should be followed up as high risk pregnancies. In summary, preeclampsia has come to be seen as a window on the future health of both mother and baby. Identification of subjects at risk, early counselling and careful follow-up can contribute to reducing the high morbidity linked with this disorder.

To investigate the literature and determine if prematurity has an impact on long-term adverse kidney outcomes.
Systematic review.
OVID Medline, PubMed, SCOPUS, CINAHL and EMBASE databases were searched for studies relating to the adverse outcomes of prematurity from 1990 to April 2021.
All articles published between January 1990 and April 2021 that investigated whether premature infants developed long-term adverse renal outcomes were included in this review. Articles must have been human studies and written in English. Case series with less than 20 participants and case studies were excluded.
One reviewer completed the database searches. Article selection was performed independently and in a non-blinded manner by both reviewers. Initial screening was by title and abstract. Full texts of remaining articles were reviewed. Articles for which inclusion was unclear were re-reviewed by both reviewers, and a unanimous decision was taken as to whether they should be included. The Newcastle-Ottawa Scale was used for quality assessment of the included articles.
The literature search yielded 31 human studies, which investigated the short-term and long-term kidney outcomes of prematurity. These studies were conducted in 17 different countries. The most common outcomes measured were blood pressure (BP) and glomerular filtration rate. Other common outcomes measured included kidney size and mass, proteinuria, albuminuria, chronic kidney disease (CKD) and physical parameters such as height, weight and body mass index.
Prematurity is likely linked to increased risk of kidney dysfunction and high BP in childhood and into early adulthood. Premature birth conferred a twofold increased risk of CKD and extremely premature birth conferred a threefold increased risk of CKD. However, further larger multicentre studies are needed to draw definitive conclusions on the long-term kidney outcomes of prematurity.