A Systematic Review of Uremic Toxin Concentrations and Cardiovascular Risk Markers in Pediatric Chronic Kidney Disease.

Chronic kidney disease (CKD) can lead to cardiac dysfunction in a condition known as cardiorenal syndrome (CRS). It is postulated that the accumulation of uremic toxins in the bloodstream, as a consequence of declining kidney function, may contribute to these adverse cardiac effects. While CRS in adults has been extensively studied, there is a significant knowledge gap with pediatric patients. Uremic toxin levels in children remain inadequately characterized and quantified compared to adults. This review aims to systematically evaluate the association between uremic toxin concentrations and cardiac changes in pediatric CRS and to examine the impact of different dialysis modalities, specifically hemodialysis and peritoneal dialysis, on uremic toxin clearance and cardiovascular parameters. To address this, we conducted a systematic literature search of PubMed, following PRISMA guidelines. We used the terms "uremic toxins" and "cardiorenal syndrome" with variations in syntax to search for studies discussing the relationship between uremic toxin levels in CKD, the subsequent impact on cardiac parameters, and the emergence of cardiac dysfunction. Full-text articles written in English, conducted on humans aged from birth to 18 years, and published until December 2021 were included. A comprehensive literature search yielded six studies, and their risk of bias was assessed using JBI Critical Appraisal Checklists. Our systematic review is registered on PROSPERO, number CRD42023460072. This synthesis intends to provide an understanding of the role of uremic toxins in pediatric CRS. The findings reveal that pediatric patients with end-stage CKD on dialysis exhibit elevated uremic toxin levels, which are significantly associated with cardiovascular disease parameters. Additionally, the severity of CKD correlated with higher uremic toxin levels. No conclusive evidence was found to support the superiority of either hemodialysis or peritoneal dialysis in terms of uremic toxin clearance or cardiovascular outcomes. More pediatric-specific standardized and longitudinal studies are needed to develop targeted treatments and improve clinical outcomes and the quality of life for affected children.

Transferability of a Bayesian Belief Network across diverse agricultural catchments using high-frequency hydrochemistry and land management data.

Biogeochemical catchment models are often developed for a single catchment and, as a result, often generalize poorly beyond this. Evaluating their transferability is an important step in improving their predictive power and application range. We assess the transferability of a recently developed Bayesian Belief Network (BBN) that simulated monthly stream phosphorus (P) concentrations in a poorly-drained grassland catchment through application to three further catchments with different hydrological regimes and agricultural land uses. In all catchments, flow and turbidity were measured sub-hourly from 2009 to 2016 and supplemented with 400-500 soil P test measurements. In addition to a previously parameterized BBN, five further model structures were implemented to incorporate in a stepwise way: in-stream P removal using expert elicitation, additional groundwater P stores and delivery, and the presence or absence of septic tank treatment, and, in one case, Sewage Treatment Works. Model performance was tested through comparison of predicted and observed total reactive P (TRP) concentrations and percentage bias (PBIAS). The original BBN accurately simulated the absolute values of observed flow and TRP concentrations in the poorly and moderately drained catchments (albeit with poor apparent percentage bias scores; 76 % ≤ PBIAS≤94 %) irrespective of the dominant land use, but performed less well in the groundwater-dominated catchments. However, including groundwater total dissolved P (TDP) and Sewage Treatment Works (STWs) inputs, and in-stream P uptake improved model performance (-5 % ≤ PBIAS≤18 %). A sensitivity analysis identified redundant variables further helping to streamline the model applications. An enhanced BBN model capable for wider application and generalisation resulted.

Cryosphere and land cover influence on stream water quality in Central Asia's glacierized catchments.

This work helps address recent calls for systematic water quality assessment in Central Asia and considers how nutrient and salinity sources, and transport, affect water quality along the continuum from the cryosphere to the lowland plains. Spatial and, for the first time, temporal variations in stream water pH, temperature, electrical conductivity, and nitrate and phosphate concentrations are presented for four catchments (485-13,500 km2), all with glaciers and major urban areas. The catchments studied were: Kaskelen (Kazakhstan), Ala-Archa (Kyrgyzstan), Chirchik (Uzbekistan) and the Kofarnihon (Tajikistan). Measurements were made in cryosphere, stream water, groundwater, reservoir and lake samples over a 22-month period at fortnightly intervals from 35 sites. The results highlight that glacier, permafrost and rock glacier outflows were primary and secondary nitrate sources (>1 mg N L-1) to the headwaters, and there were major increases in salinity and nitrate concentrations where rivers receive inputs from agriculture and settlements. Overall, the water quality complied with national and World Health Organization standards, however there were pollution hot-spots with shallow urban groundwaters contaminated with nitrate (>11 mg N L-1) and stream electrical conductivity above 800 µS cm-1 in some agricultural areas indicative of high salinity. Phosphate concentrations were generally low (<0.06 mg P L-1) throughout the catchments, though elevated (>0.2 mg P L-1) in urban areas due to effluent contamination. A melt water dilution effect along the main river channels was discernible, in the electrical conductivity and nitrate concentration seasonal dynamics, 100 s of km from the headwaters. Thus, the input of relatively clean water from the cryosphere is an important regulator of main channel water quality in the urban and farmed lowland plains adjacent to the Tien Shan and Pamir. Improved sewage treatment is needed in urban areas.

Non-invasive biomarkers of disease activity and organ damage in ANCA-associated vasculitis: a systematic review.

BACKGROUND: In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), histopathological assessment of affected tissue is often necessary for diagnosis and assessment of disease extent. There is a requirement for validated non-invasive biomarkers to avoid the need for serial tissue biopsies. METHODS: A systematic review of scientific databases from 2012 until present was performed to identify studies fulfilling the inclusion criteria. Studies were assessed for quality using the Strengthening the Reporting of Observational Studies in Epidemiology checklist for cohort, case-control and cross-sectional studies and the Risk of Bias Assessment tool for Non-randomised Studies, or the Cochrane Risk of Bias tool 2.0 for randomised controlled trials. A descriptive synthesis of the data for non-invasive (blood-based or urinary) biomarkers of AAV-related disease activity and organ damage was performed. RESULTS: Twenty-two high quality studies were included. These articles reported the value of blood-based and urinary biomarkers including anti-neutrophil cytoplasmic antibodies, immune cells, complement factors, gene expression profiles, cytokines, chemokines and other proteins in the assessment of disease activity and/or organ damage in patients with AAV. Many of these biomarkers involve the alternative complement pathway, neutrophil activation and macrophage activation. CONCLUSION: This is the first contemporary systematic review synthesising the value of non-invasive biomarkers of AAV-related disease activity and organ damage. The incorporation of individual markers in combined biomarker profiles might enhance clinical decision-making. Many unmet needs were identified; few studies involve oeosinophilic granulomatosis with polyangiitis and patients with childhood-onset AAV. Further validation of the candidate biomarkers is warranted in large prospective studies to bridge the existing knowledge gaps and apply precision health to systemic vasculitis.

The effect of dehydration, hyperchloremia and volume of fluid resuscitation on acute kidney injury in children admitted to hospital with diabetic ketoacidosis.

BACKGROUND: Acute kidney injury (AKI) is a recognized comorbidity in pediatric diabetic ketoacidosis (DKA), although the exact etiology is unclear. The unique physiology of DKA makes dehydration assessments challenging, and these patients potentially receive excessive amounts of intravenous fluids (IVF). We hypothesized that dehydration is over-estimated in pediatric DKA, leading to over-administration of IVF and hyperchloremia that worsens AKI. METHODS: Retrospective cohort of all DKA inpatients at a tertiary pediatric hospital from 2014 to 2019. A total of 145 children were included; reasons for exclusion were pre-existing kidney disease or incomplete medical records. AKI was determined by change in creatinine during admission, and comparison to a calculated baseline value. Linear regression multivariable analysis was used to identify factors associated with AKI. True dehydration was calculated from patients' change in weight, as previously validated. Fluid over-resuscitation was defined as total fluids given above the true dehydration. RESULTS: A total of 19% of patients met KDIGO serum creatinine criteria for AKI on admission. Only 2% had AKI on hospital discharge. True dehydration and high serum urea levels were associated with high serum creatinine levels on admission (p = 0.042; p < 0.001, respectively). Fluid over-resuscitation and hyperchloremia were associated with delayed kidney recovery (p < 0.001). Severity of initial AKI was associated with cerebral edema (p = 0.018). CONCLUSIONS: Dehydration was associated with initial AKI in children with DKA. Persistent AKI and delay to recovery was associated with hyperchloremia and over-resuscitation with IVF, potentially modifiable clinical variables for earlier AKI recovery and reduction in long-term morbidity. This highlights the need to re-address fluid protocols in pediatric DKA.

Subfemtowatt Laser Phase Tracking.

Low power optical phase tracking is an enabling capability for intersatellite laser interferometry, as minimum trackable power places significant constraints on mission design. Through the combination of laser stabilization and control-loop parameter optimization, we have demonstrated continuous tracking of a subfemtowatt optical field with a mean time between slips of more than 1000 s. Comparison with analytical models and numerical simulations verified that the observed experimental performance was limited by photon shot noise and unsuppressed laser frequency fluctuations. Furthermore, with two stabilized lasers, we have demonstrated 100 min of continuous phase tracking of Gravity Recovery and Climate Experiment (GRACE)-like signal dynamics with an optical carrier ranging in power between 1-7 fW with zero cycle slips. These results indicate the feasibility of future interspacecraft laser links operating with significantly reduced received optical power.

Hyperchloremia and association with acute kidney injury in critically ill children.

BACKGROUND: Hyperchloremia has been associated with acute kidney injury (AKI) in critically ill adult patients. Data is limited in pediatric patients. Our study sought to determine if an association exists between hyperchloremia and AKI in pediatric patients admitted to the intensive care unit (PICU). METHODS: This is a single-center retrospective cohort study of pediatric patients admitted to the PICU for greater than 24 h and who received intravenous fluids. Patients were excluded if they had a diagnosis of kidney disease or required kidney replacement therapy (KRT) within 6 h of admission. Exposures were hyperchloremia (serum chloride ≥ 110 mmol/L) within the first 7 days of PICU admission. The primary outcome was the development of AKI using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Secondary outcomes included time on mechanical ventilation, new KRT, PICU length of stay, and mortality. Outcomes were analyzed using multivariate logistic regression. RESULTS: There were 407 patients included in the study, 209 in the hyperchloremic group and 198 in the non-hyperchloremic group. Univariate analysis demonstrated 108 (51.7%) patients in the hyperchloremic group vs. 54 (27.3%) in the non-hyperchloremic group (p = < .001) with AKI. On multivariate analysis, the odds ratio of AKI with hyperchloremia was 2.24 (95% CI 1.39-3.61) (p = .001). Hyperchloremia was not associated with increased odds of mortality, need for KRT, time on mechanical ventilation, or length of stay. CONCLUSION: Hyperchloremia was associated with AKI in critically ill pediatric patients. Further pediatric clinical trials are needed to determine the benefit of a chloride restrictive vs. liberal fluid strategy. A higher resolution version of the Graphical abstract is available as Supplementary information.

Absolute frequency readout derived from ULE cavity for next generation geodesy missions: erratum.

We found a calculation error affecting the scaling of results presented in Figure 7 of our article "Absolute frequency readout derived from ULE cavity for next generation geodesy missions" [Opt. Express2926014 (2021)10.1364/OE.434483] . The corrected Figure 7 is published here.

Paediatric Dialysis at a Tertiary Hospital in South-West Nigeria: A 4-Year Report.

INTRODUCTION: Dialysis is potentially lifesaving in children with acute kidney injury (AKI) or chronic kidney disease (CKD), but availability is limited in low-income countries and lower-middle-income countries (LMICs). METHODS: In the present study, we perform a 4-year study of patients who received peritoneal dialysis (PD) or haemodialysis (HD) at the Paediatric Nephrology Unit of the University College Hospital Ibadan, Nigeria. Subgroup analysis was performed on patients with sepsis or malaria AKI who underwent HD or PD for predictors of in-hospital mortality. RESULTS: A total of 167 children aged 7 days to 18 years, median 7 (interquartile range 3-12) years, (60.5% males) were studied. In total, 129 (77.2%) had AKI, while 38 had CKD. Regarding AKI, 83 children (64.3%) received HD only, 42 underwent PD only, while 4 underwent both HD and PD. Malaria AKI was treated with HD in 43 (51.8%) or PD in 8 (10.5%), while sepsis AKI was treated with HD in 20 (21.4%) or PD in 33 (78.6%). Mortality in AKI was 16.3% overall, 10.8% in children on HD only, and 26.2% in children on PD only. Patients with sepsis AKI had higher mortality compared to patients with malaria AKI (RR 7.96 [1.70-37.37]). Subgroup analysis showed that age, diagnosis, and dialysis modality were not independent risk factors for mortality. The aetiology of CKD was glomerulonephritis in 26 (68.4%): treatment was HD in 36 and PD in 2 with mortality being 26.3%. CONCLUSIONS: PD for AKI showed relatively good outcomes in a LMIC. However, funding and support for a formal dialysis program for the management of AKI and CKD are needed.

Absolute frequency readout derived from ULE cavity for next generation geodesy missions.

The next generation of Gravity Recovery and Climate Experiment (GRACE)-like dual-satellite geodesy missions proposals will rely on inter-spacecraft laser interferometry as the primary instrument to recover geodesy signals. Laser frequency stability is one of the main limits of this measurement and is important at two distinct timescales: short timescales over 10-1000 seconds to measure the local gravity below the satellites, and at the month to year timescales, where the subsequent gravity measurements are compared to indicate loss or gain of mass (or water and ice) over that period. This paper demonstrates a simple phase modulation scheme to directly measure laser frequency change over long timescales by comparing an on-board Ultra-Stable Oscillator (USO) clocked frequency reference to the Free Spectral Range (FSR) of the on-board optical cavity. By recording the fractional frequency variations the scale correction factor may be computed for a laser locked to a known longitudinal mode of the optical cavity. The experimental results demonstrate a fractional absolute laser frequency stability at the 10 ppb level (10-8) at time scales greater than 10 000 seconds, likely sufficient for next generation mission requirements.

High stability laser locking to an optical cavity using tilt locking.

This paper describes, to our knowledge, the first demonstration of high performance tilt locking, a method of stabilizing laser frequency to an optical reference cavity using a spatial-mode readout technique. The experiment utilized a traveling wave cavity with a finesse of approximately 10,000, housed in a thermally controlled vacuum chamber. The tilt locking method in a double pass configuration has promising performance in the 100 µHz-1 Hz band, including surpassing the Gravity Recovery and Climate Experiment (GRACE) Follow-On laser ranging interferometer requirement. Tilt locking offers a number of benefits such as high sensitivity, low cost, and simple implementation and therefore should be considered for future applications requiring high performance laser locking, such as future laser-based satellite geodesy missions and the Laser Interferometer Space Antenna.

Spatial properties affecting the sensitivity of soil water dissolved organic carbon long-term median concentrations and trends.

It is increasingly clear that increases in dissolved organic carbon in upland waters in recent decades have often been dominated by acid deposition, but reasons for substantial variation in rates of change remain unclear. This paper focuses on the extent to which spatial properties, such as variation in soil properties, atmospheric deposition and climate, affect the sensitivity of DOC concentrations in soil water. The purpose is to i) examine evidence for differences in site average concentrations and trends in soil water DOC between sites with contrasting ecosystem properties, i.e. vegetation cover and soil type, and ii) identify the wider combination of site characteristics that best explain variation in these DOC metrics between sites. We collated soil water and deposition chemistry, soil chemistry and meteorological data from 15 long-term UK monitoring sites (1992-2010) covering a range of soils, vegetation, climate and acid deposition levels. Mineral soils under forests showed the greatest range of long-term mean DOC concentrations and trends. Regression analysis indicated that acid and sea-salt deposition, and soil sensitivity to acidification were the factors most strongly associated with spatial variation in mean DOC concentrations. Spatial variation in DOC trends were best explained by Al saturation and water flux. Overall, the sensitivity of DOC release from soil to changes in pollutant deposition could be related to the type of vegetation cover and soils chemistry properties, such as Al saturation, divalent base cation content and hydrological regime. The identification of the ecosystem properties that appear most influential in modifying DOC production and responses to long-term drivers, helps elucidate potential mechanistic explanations for differences in DOC dynamics across seemingly similar ecosystems, and points to the importance of DOC mobility in regulating its dynamics.

A Bayesian network to simulate macroinvertebrate responses to multiple stressors in lowland streams.

Aquatic ecosystems are affected by multiple environmental stressors across spatial and temporal scales. Yet the nature of stressor interactions and stressor-response relationships is still poorly understood. This hampers the selection of appropriate restoration measures. Hence, there is a need to understand how ecosystems respond to multiple stressors and to unravel the combined effects of the individual stressors on the ecological status of waterbodies. Models may be used to relate responses of ecosystems to environmental changes as well as to restoration measures and thus provide valuable tools for water management. Therefore, we aimed to develop and test a Bayesian Network (BN) for simulating the responses of stream macroinvertebrates to multiple stressors. Although the predictive performance may be further improved, the developed model was shown to be suitable for scenario analyses. For the selected lowland streams, an increase in macroinvertebrate-based ecological quality (EQR) was predicted for scenarios where the streams were relieved from single and multiple stressors. Especially a combination of measures increasing flow velocity and enhancing the cover of coarse particulate organic matter showed a significant increase in EQR compared to current conditions. The use of BNs was shown to be a promising avenue for scenario analyses in stream restoration management. BNs have the capacity for clear visual communication of model dependencies and the uncertainty associated with input data and results and allow the combination of multiple types of knowledge about stressor-effect relations. Still, to make predictions more robust, a deeper understanding of stressor interactions is required to parametrize model relations. Also, sufficient training data should be available for the water type of interest. Yet, the application of BNs may now already help to unravel the contribution of individual stressors to the combined effect on the ecological quality of water bodies, which in turn may aid the selection of appropriate restoration measures that lead to the desired improvements in macroinvertebrate-based ecological quality.

Canadian Association of Paediatric Nephrologists COVID-19 Rapid Response: Guidelines for Management of Acute Kidney Injury in Children.

PURPOSE: This article provides guidance on managing acute kidney injury (AKI) and kidney replacement therapy (KRT) in pediatrics during the COVID-19 pandemic in the Canadian context. It is adapted from recently published rapid guidelines on the management of AKI and KRT in adults, from the Canadian Society of Nephrology (CSN). The goal is to provide the best possible care for pediatric patients with kidney disease during the pandemic and ensure the health care team's safety. INFORMATION SOURCES: The Canadian Association of Paediatric Nephrologists (CAPN) COVID-19 Rapid Response team derived these rapid guidelines from the CSN consensus recommendations for adult patients with AKI. We have also consulted specific documents from other national and international agencies focused on pediatric kidney health. We identified additional information by reviewing the published academic literature relevant to pediatric AKI and KRT, including recent journal articles and preprints related to COVID-19 in children. Finally, our group also sought expert opinions from pediatric nephrologists across Canada. METHODS: The leadership of the CAPN, which is affiliated with the CSN, solicited a team of clinicians and researchers with expertise in pediatric AKI and acute KRT. The goal was to adapt the guidelines recently adopted for Canadian adult patients for pediatric-specific settings. These included specific COVID-19-related themes relevant to AKI and KRT in a Canadian setting, as determined by a group of kidney disease experts and leaders. An expert group of clinicians in pediatric AKI and acute KRT reviewed the revised pediatric guidelines. KEY FINDINGS: (1) Current Canadian data do not suggest an imminent threat of an increase in acute KRT needs in children because of COVID-19; however, close coordination between nephrology programs and critical care programs is crucial as the pandemic continues to evolve. (2) Pediatric centers should prepare to reallocate resources to adult centers as needed based on broader health care needs during the COVID-19 pandemic. (3) Specific suggestions pertinent to the optimal management of AKI and KRT in COVID-19 patients are provided. These suggestions include but are not limited to aspects of fluid management, KRT vascular access, and KRT modality choice. (4) Considerations to ensure adequate provision of KRT if resources become scarce during the COVID-19 pandemic. LIMITATIONS: We did not conduct a formal systematic review or meta-analysis. We did not evaluate our specific suggestions in the clinical environment. The local context, including how the provision of care for AKI and acute KRT is organized, may impede the implementation of many suggestions. As knowledge is advancing rapidly in the area of COVID-19, suggestions may become outdated quickly. Finally, most of the literature for AKI and KRT in COVID-19 comes from adult data, and there are few pediatric-specific studies. IMPLICATIONS: Given that most acute KRT related to COVID-19 is likely to be required in the pediatric intensive care unit initial setting, close collaboration and planning between critical care and pediatric nephrology programs are needed. Our group will update these suggestions with a supplement if necessary as newer evidence becomes available that may change or add to the recommendations provided.

Altered supraspinal motor networks in survivors of poliomyelitis: A cortico-muscular coherence study.

OBJECTIVE: Poliomyelitis results in changes to the anterior horn cell. The full extent of cortical network changes in the motor physiology of polio survivors has not been established. Our aim was to investigate how focal degeneration of the lower motor neurons (LMN) in infancy/childhood affects motor network connectivity in adult survivors of polio. METHODS: Surface electroencephalography (EEG) and electromyography (EMG) were recorded during an isometric pincer grip task in 25 patients and 11 healthy controls. Spectral signal analysis of cortico-muscular (EEG-EMG) coherence (CMC) was used to identify the cortical regions that are functionally synchronous and connected to the periphery during the pincer grip task. RESULTS: A pattern of CMC was noted in polio survivors that was not present in healthy individuals. Significant CMC in low gamma frequency bands (30-47 Hz) was observed in frontal and parietal regions. CONCLUSION: These findings imply a differential engagement of cortical networks in polio survivors that extends beyond the motor cortex and suggest a disease-related functional reorganisation of the cortical motor network. SIGNIFICANCE: This research has implications for other similar LMN conditions, including spinal muscular atrophy (SMA). CMC has potential in future clinical trials as a biomarker of altered function in motor networks in post-polio syndrome, SMA, and other related conditions.

Diagnosis by consensus: A case study in the importance of interdisciplinary interpretation of mummified remains.

OBJECTIVE: The goal of this study is to demonstrate the need for interdisciplinary consensus and inclusion of mummy radiology specialists in analyses of mummified remains. MATERIALS: This study uses paleoimaging data for an ancient Egyptian mummy at the Museum of Human Anatomy "Filippo Civinini". METHODS: This study demonstrates the benefit of evaluation of mummified remains in a multi-disciplinary interpretive team. RESULTS: The authors propose a diagnosis of DISH, additional signs of undifferentiated spondyloarthropathy, and lumbarisation of S1. CONCLUSIONS: The process of diagnosis by consensus is essential to the analysis of mummified remains, which are complexly altered through natural and anthropogenic processes in the millennia subsequent to the individual's death. SIGNIFICANCE: Mummy paleoimaging and paleopathology lacks a unifying set of standards. We present an example of the value to be found in the multi-disciplinary diagnosis by consensus approach. LIMITATIONS: We discuss numerous challenges to accurate and meaningful interpretation that radiography of mummified remains pose. SUGGESTIONS FOR FURTHER RESEARCH: While the authors do not seek to impose any single set of standards, we do recommend a larger discussion on the topic of (culture-specific) standardisation in mummy paleoimaging and paleopathology. We further recommend the development of an international, multi-disciplinary panel of paleoimaging interpreters.

Responses of Aquatic Plants to Eutrophication in Rivers: A Revised Conceptual Model.

Compared to research on eutrophication in lakes, there has been significantly less work carried out on rivers despite the importance of the topic. However, over the last decade, there has been a surge of interest in the response of aquatic plants to eutrophication in rivers. This is an area of applied research and the work has been driven by the widespread nature of the impacts and the significant opportunities for system remediation. A conceptual model has been put forward to describe how aquatic plants respond to eutrophication. Since the model was created, there have been substantial increases in our understanding of a number of the underlying processes. For example, we now know the threshold nutrient concentrations at which nutrients no longer limit algal growth. We also now know that the physical habitat template of rivers is a primary selector of aquatic plant communities. As such, nutrient enrichment impacts on aquatic plant communities are strongly influenced, both directly and indirectly, by physical habitat. A new conceptual model is proposed that incorporates these findings. The application of the model to management, system remediation, target setting, and our understanding of multi-stressor systems is discussed. We also look to the future and the potential for new numerical models to guide management.

Glomerular Filtration Rate Trends During Follow-up in Children With Steroid-Sensitive Nephrotic Syndrome.

BACKGROUND: Overall prognosis of children with steroid-sensitive nephrotic syndrome (SSNS) is regarded as generally favorable. However, only a few recent studies have evaluated changes in kidney function and blood pressure over time in children with SSNS. OBJECTIVES: We describe clinical features of SSNS patients and characterize changes in calculated estimated glomerular filtration rate (eGFR) and use of antihypertensive medications during follow-up. DESIGN: This is a retrospective cohort study. SETTING: This study was conducted in a Canadian pediatric nephrology center. PATIENTS: This study included patients aged 1 to 18 years with SSNS. MEASUREMENTS: eGFR was calculated from recorded serum creatinine and height measurements using the modified Schwartz equation. METHODS: eGFR was calculated at yearly intervals, and the trend of eGFR was assessed using linear mixed effects model. Patients were also evaluated for use of antihypertensive medications during follow-up. RESULTS: Seventy-eight patients-median age, 3.2 years (interquartile range [IQR], 2.65) and median follow-up of 4.37 (IQR, 5.6)-were evaluated. Sixty-three (80.8%) had at least 1 relapse. Twenty-two (28.2%) and 20 (25.6%) were steroid dependent and frequently relapsing, respectively. Forty-three patients (55.1%) received at least 1 steroid-sparing agent, and of these, 18 (41.8%) received a calcineurin inhibitor. One patient had eGFR ≤90 mL/min/1.73 m2 during observation. eGFR remained unchanged over the follow-up period in this cohort of patients. Four patients (5.1%) were on antihypertensive medications at the end of follow-up. LIMITATIONS: Patients who had frequent relapses had more measurements available for serum creatinine and height, creating a sampling bias. The number of eGFR measurements was overall small, making it difficult to ascertain eGFR trend. CONCLUSION: eGFR remained unchanged over time in this cohort, and a small proportion of patients required antihypertensive therapy at the end of follow-up. Our study highlights the needs for carefully constructed long-term observational studies of children with nephrotic syndrome.

MISE EN CONTEXTE: De manière générale, on considère le pronostic du syndrome néphrotique stéroïdosensible chez l'enfant comme favorable. Toutefois, seules quelques études récentes ont mesuré les changements dans la fonction rénale et la pression sanguine au fil du temps chez les enfants atteints du syndrome néphrotique stéroïdosensible. OBJECTIFS DE L'ÉTUDE: Décrire les manifestations cliniques du syndrome néphrotique stéroïdosensible, de même que caractériser les changements dans le débit de filtration glomérulaire estimé (DFGe) et la prise de médicaments contre l'hypertension au cours de la période de suivi. CADRE ET TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte prospective qui s'est tenue dans un centre de néphrologie pédiatrique canadien. PATIENTS: Des enfants âgés de 1 à 18 ans atteints du syndrome néphrotique stéroïdosensible. MESURES: On a utilisé l'équation de Schwartz modifiée pour calculer le DFGe des participants à partir de leur taille et de mesures de créatinine sérique déjà enregistrées. MÉTHODOLOGIE: On a procédé au calcul du DFGe chaque année et on en a évalué la tendance à l'aide d'un modèle linéaire à effets mixtes. La prise de médicaments contre l'hypertension a également été évaluée au cours de la période du suivi. RÉSULTATS: Un total de 78 patients, dont l'âge médian se situait à 3,2 ans (écart interquartile = 2,65 ans), ont été évalués sur une période de 4,37 ans (EI = 5,6 ans) en moyenne, desquels 80,8% (63 patients) ont fait au moins une rechute. Des patients évalués, 28,2% (n = 22) étaient dépendants des stéroïdes et 25,6% (n = 20) faisaient des rechutes fréquentes. Quarante-trois patients (55,1%) ont reçu au moins un agent de préservation de stéroïdes, dont dix-huit (41,8%) ont reçu un inhibiteur de la calcineurine. Un seul patient a présenté une valeur de DFGe de plus de 90 ml/min/1,73 m2 au cours de la période d'observation. Le DFGe est demeuré inchangé tout au long de la période de suivi pour cette cohorte. À la fin de la période de suivi, quatre patients (5,1%) prenaient des médicaments contre l'hypertension. LIMITES DE L'ÉTUDE: Un biais d'échantillonnage est introduit par le fait qu'un nombre plus élevé de mesures de taille et de DFGe étaient disponibles pour les patients ayant fait plusieurs rechutes. Par ailleurs, l'établissement de tendances en regard des valeurs de DFGe s'avère difficile étant donné le nombre relativement faible de mesures disponibles. CONCLUSIONS: Les valeurs de DFGe sont demeurées inchangées tout au long de la période de suivi pour cette cohorte de patients, et seulement quatre d'entre eux ont dû être traités pour l'hypertension à la fin du suivi. Cette étude met en lumière le besoin pour la tenue d'études observationnelles à long terme et judicieusement élaborées chez les enfants atteints du syndrome néphrotique stéroïdosensible.

Factors influencing practice variation in the management of nephrotic syndrome: a qualitative study of pediatric nephrology care providers.

BACKGROUND: Treatment protocols for childhood nephrotic syndrome are highly variable between providers and care centres. We conducted a qualitative study to understand the complex multilevel processes that lead to practice variation and influence provider management of nephrotic syndrome. METHODS: Focus groups with multidisciplinary pediatric nephrology care providers (n = 67) from 10 Canadian pediatric nephrology centres that had more than 1 pediatric nephrologist were conducted between September 2013 and April 2015. Focus group discussions were guided by the Ottawa Model for Research Use. We used a semistructured interview guide to elicit participants' perspectives regarding 1) the work setting and context of the clinical environment, 2) reasons for variation at the provider level and 3) clinical practice guidelines for nephrotic syndrome. Focus group discussions were transcribed and analyzed concurrently with the use of qualitative content analysis. RESULTS: Emerging themes were grouped into 2 categories: centre-level factors and provider-level factors. At the centre level, the type of care model used, clinic structures and resources, and lack of communication and collaboration within and between Canadian centres influenced care variation. At the provider level, use of experiential knowledge versus empirical knowledge and interpretation of patient characteristics influenced provider management of nephrotic syndrome. INTERPRETATION: Centre- and provider-level factors play an important role in shaping practice differences in the management of childhood nephrotic syndrome. Further research is needed to determine whether variation in care is associated with disparities in outcomes.