A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

BACKGROUND: Vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (ICU) and associated with worse clinical course. Trials in adult ICU demonstrate rapid restoration of vitamin D status using an enteral loading dose is safe and may improve outcomes. There have been no published trials of rapid normalization of VDD in the pediatric ICU. METHODS: We conducted a multicenter placebo-controlled phase II pilot feasibility randomized clinical trial from 2016 to 2017. We randomized 67 critically ill children with VDD from ICUs in Canada, Chile and Austria using a 2:1 randomization ratio to receive a loading dose of enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or placebo. Participants, care givers, and outcomes assessors were blinded. The primary objective was to determine whether the loading dose normalized vitamin D status (25(OH)D > 75 nmol/L). Secondary objectives were to evaluate for adverse events and assess the feasibility of a phase III trial. RESULTS: Of 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary analyses (40 treatment, 19 placebo). Thirty-one/38 (81.6%) participants in the treatment arm achieved a plasma 25(OH)D concentration > 75 nmol/L versus 1/18 (5.6%) the placebo arm. The mean 25(OH)D concentration in the treatment arm was 125.9 nmol/L (SD 63.4). There was no evidence of vitamin D toxicity and no major drug or safety protocol violations. The accrual rate was 3.4 patients/month, supporting feasibility of a larger trial. A day 7 blood sample was collected for 84% of patients. A survey administered to 40 participating families showed that health-related quality of life (HRQL) was the most important outcome for families for the main trial (30, 75%). CONCLUSIONS: A single 10,000 IU/kg dose can rapidly and safely normalize plasma 25(OH)D concentrations in critically ill children with VDD, but with significant variability in 25(OH)D concentrations. We established that a phase III multicentre trial is feasible. Using an outcome collected after hospital discharge (HRQL) will require strategies to minimize loss-to-follow-up. CLINICALTRIALS: gov NCT02452762 Registered 25/05/2015.

Furosemide and albumin for the treatment of nephrotic edema: a systematic review.

BACKGROUND: Edema is one of the cardinal clinical features of nephrotic syndrome (NS). It may vary from mild periorbital edema to severe generalized edema (anasarca). In patients where edema does not improve with prednisone therapy, the most common supportive medications are diuretics and albumin. However, due to the complex pathophysiology of edema formation in NS patients resulting in intravascular normovolemia or hypovolemia, optimal therapy for edema is still debated. We conducted a systematic review with the objective of evaluating the change in urine volume and urine sodium excretion after treatment with furosemide only versus furosemide with albumin in edematous patients with NS. OBJECTIVES: (1) To evaluate efficacy of furosemide alone versus furosemide with albumin in the treatment of nephrotic edema in adults and children. (2) To compare the harms and benefits of different doses of furosemide for treating nephrotic edema. SEARCH METHODS: The search included all randomized or quasi-randomized controlled trials in English and French using MEDLINE, Embase, and CENTRAL Trials Registry of the Cochrane Collaboration using the Ovid interface. CLINICALTRIALS: gov and the International Clinical Trials Registry Platform were also searched. SELECTION CRITERIA: We included all RCTs and randomized cross-over studies in which furosemide and furosemide plus albumin are used in the treatment of children or adults with nephrotic edema. We excluded patients with hypoalbuminemia of non-renal origin and severe chronic kidney disease (CKD) with a glomerular filtration rate below 30 ml/min/1.74 m2 and patients with congenital NS. DATA COLLECTION AND ANALYSIS: All abstracts were independently assessed by at least two authors to determine which studies met the inclusion criteria. Information on study design, methodology, and outcome data (urine volume, urine sodium excretion, adverse effects) from each identified study was entered into a separate data sheet. The differences in outcomes between the types of therapy were expressed as standardized mean difference (SMD) with 95% confidence intervals (CI). RESULTS: The search yielded 525 records, and after screening, five studies were included in the systematic review and four of those studies in the meta-analysis. One study had high risk of bias and the remaining three studies were deemed to have some concerns. Urine excretion was greater after treatment with furosemide and albumin versus furosemide (SMD 0.85, 95% CI = 0.33 to 1.38). Results for sodium excretion were inconclusive (SMD 0.37, 95%CI = - 0.28 to 1.02). AUTHORS' CONCLUSIONS: The current evidence is not sufficient to make definitive conclusions about the role of albumin in treating nephrotic edema. High-quality randomized studies with adequate samples sizes are needed. Including an assessment of intravascular volume status may be helpful. TRIAL REGISTRATION: Prospero: CRD4201808979. https://www.crd.york.ac.uk/PROSPERO A higher resolution version of the Graphical abstract is available as Supplementary information.

Diastolic hypertension is associated with proteinuria in pediatric patients.

BACKGROUND AND AIMS: Blood pressure lability has been observed in certain cohorts of pediatric patients with variable degrees of proteinuria; however, the impact of proteinuria on blood pressure is not fully elucidated. The objective of our study was to analyze blood pressure and heart rate in pediatric patients with proteinuria. METHODS: We performed a retrospective chart review of patients (age 1-18) diagnosed with idiopathic nephrotic syndrome, with varying degrees of proteinuria. Blood pressure and heart rate data were analyzed in relation to anthropometric and biochemical parameters. A total of 72 urine sample analyses, along with associated blood pressure measurements, were obtained from the charts of 33 children (males = 25). RESULTS: Diastolic blood pressure Z-scores were significantly higher in proteinuric patients (urine protein/creatinine >0.02 g/mmol) compared to non-proteinuric patients (P = .006; Cohen-d 0.97 [0.41; 1.53]). Systolic blood pressure was also significantly higher in proteinuric patients (P = .04), but with a less significant effect size (Cohen-d 0.54 [-0.002; 1.08]). Proteinuria (>0.02 g/mmol) was the most significant predictor of diastolic (ß = .79, P = .04), but not systolic blood pressure elevation on multivariate analysis. CONCLUSIONS: We observed a disproportionate increase in diastolic blood pressure vs systolic blood pressure in patients with proteinuria.

Renal function in children with a congenital solitary functioning kidney: A systematic review.

INTRODUCTION: Abnormal renal development that results in lack of function or development of one of two kidneys is known as congenital solitary functioning kidney (CSFK). Two well characterized sub-categories of CFSK are unilateral renal agenesis (URA) and multicystic dysplastic kidney (MCDK). This systematic review sought to evaluate the change in renal function in children ≤18 years old with a CSFK as a result of URA or MCDK. METHODS: A literature search in MEDLINE and Embase was conducted (1946 to July 13, 2020). All relevant articles were retrieved and evaluated based on pre-selected criteria by two independent researchers. Data was then extracted from variables of interest and conflicts were resolved by a third researcher. The primary outcome was renal function, and the secondary outcomes were proteinuria and hypertension. RESULTS: Forty-five studies were included, of which 49% (n = 22) were retrospective and/or 58% (n = 26) were cohort studies. A combined total of 2148 and 885 patients were diagnosed with MCDK or URA, respectively. The proportion of children with worsened renal function at follow-up was found to be 8.4% (95% CI: 5.2%-13.4%). Among the studies reporting renal function as a group mean or median at follow-up, 84% (21/25) had a GFR/CrCl above 90 (mL/min/1.73  m2/ml/min). In terms of secondary outcomes, the proportion of children with proteinuria and hypertension was found to be 10.1% (95% CI: 6.9%-14.6%) and 7.4% (95% CI: 5.0%-10.9%), respectively. CONCLUSION: The risk of developing proteinuria (10.1%), hypertension (7.4%), and/or worsened renal function (8.4%) for children with CFSK as a result of MCDK or URA is low. However, the level of evidence in the literature is weak. Further research is needed to identify the predisposing factors that may differentiate the small subset of children with CSFK at a higher risk of developing adverse renal outcomes.

Prevention of post-cardiac surgery vitamin D deficiency in children with congenital heart disease: a pilot feasibility dose evaluation randomized controlled trial.

BACKGROUND: The vast majority of children undergoing cardiac surgery have low vitamin D levels post-operative, which may contribute to greater illness severity and worse clinical outcomes. Prior to the initiation of a large phase III clinical trial focused on clinical outcomes, studies are required to evaluate the feasibility of the study protocol, including whether the proposed dosing regimen can safely prevent post-operative vitamin D deficiency in this high-risk population. METHODS: We conducted a two-arm, double-blind dose evaluation randomized controlled trial in children requiring cardiopulmonary bypass for congenital heart disease. Pre-operatively, participants were randomized to receive cholecalciferol representing usual care (< 1 year = 400 IU/day, > 1 year = 600 IU/day) or a higher dose approximating the Institute of Medicine tolerable upper intake level (< 1 year = 1600 IU/day, > 1 year = 2400 IU/day). The feasibility outcomes were post-operative vitamin D status (primary), vitamin D-related adverse events, accrual rate, study withdrawal rate, blinding, and protocol non-adherence. RESULTS: Forty-six children were randomized, and five withdrew prior to surgery, leaving 41 children (21 high dose, 20 usual care) in the final analysis. The high dose group had higher 25-hydroxyvitamin D concentrations both intraoperatively (mean difference + 25.9 nmol/L; 95% CI 8.3-43.5) and post-operatively (mean difference + 17.2 nmol/L; 95% CI 5.5-29.0). Fewer participants receiving high-dose supplementation had post-operative serum 25-hydroxyvitamin D concentrations under 50 nmol/L, compared with usual care (RR 0.31, 95% CI 0.11-0.87). Post-operative vitamin D status was associated with the treatment arm and the number of doses received. There were no cases of hypercalcemia, and no significant adverse events related to vitamin D. While only 75% of the target sample size was recruited (limited funding), the consent rate (83%), accrual rate (1.5 per site month), number of withdrawals (11%), and ability to maintain blinding support feasibility of a larger trial. CONCLUSIONS: Pre-operative daily high-dose supplementation improved vitamin D status pre-operatively and at time of pediatric ICU admission. The protocol for a more definitive trial should limit enrollment of children with at least 30 days between randomization and surgery to allow adequate duration of supplementation or consider a loading dose. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01838447. Registered on April 24, 2013.

Association of infections and venous thromboembolism in hospitalized children with nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) results in hypercoagulability and increased risk of infection. Furthermore, infection increases the risk of venous thromboembolism (VTE). Our objective was to determine the prevalence of infection, VTE, and the associated outcomes among a cohort of hospitalized children with NS. METHODS: All children with NS admitted to 17 pediatric hospitals across North America from 2010 to 2012 were included. Prevalence of infection and VTE was determined. Wilcoxon rank-sum and logistic regression were performed. RESULTS: Seven-hundred thirty hospitalizations occurred among 370 children with NS. One-hundred forty-eight children (40%) had ≥ 1 infection (211 episodes) and 11 (3%) had VTE. Those with VTE had infection more frequently (p = 0.046) and were younger at NS diagnosis (3.0 vs. 4.0 years; p = 0.008). The most common infectious pathogen identified was Streptococcus pneumoniae. The median hospital length of stay for those with infection [10 vs 5 days (p < 0.0001)] or VTE [22 vs 6 days (p < 0.0001)] was longer than those without either complication. Of those with infection, 13% had an intensive care unit (ICU) stay compared with 3.3% of those without infection. Median ICU stay was 4 days in those with VTE compared to 0 days in those without (p < 0.001). By logistic regression, only the number of ICU days was associated with VTE (OR 1.074, 95% CI 1.013-1.138). CONCLUSIONS: Hospitalized children with NS have high rates of infection. Presence of VTE was associated with infection. Both were associated with longer hospitalizations and ICU stays.

Study protocol for a phase II dose evaluation randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

BACKGROUND: Clinical research has recently demonstrated that vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (PICU) and associated with worse clinical course. Multiple adult ICU trials have suggested that optimization of vitamin D status through high-dose supplementation may reduce mortality and improve other clinically relevant outcomes; however, there have been no trials of rapid normalization in the PICU setting. The objective of this study is to evaluate the safety and efficacy of an enteral weight-based cholecalciferol loading dose regimen in critically ill children with VDD. METHODS/DESIGN: The VITdAL-PICU pilot study is designed as a multicenter placebo-controlled phase II dose evaluation pilot randomized controlled trial. We aim to randomize 67 VDD critically ill children using a 2:1 randomization schema to receive loading dose enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or a placebo solution. Participants, caregivers and outcome assessors will be blinded to allocation. Eligibility criteria include ICU patient, aged 37 weeks to 18 years, expected ICU length of stay more than 48 h, anticipated access to bloodwork at 7 days, and VDD (blood total 25 hydroxyvitamin D < 50 nmol/L). The primary objective is to determine whether the dosing protocol normalizes vitamin D status, defined as a blood total 25(OH)D concentration above 75 nmol/L. Secondary objectives include an examination of the safety of the dosing regimen (e.g. hypercalcemia, hypercalciuria, nephrocalcinosis), measures of vitamin D axis function (e.g. calcitriol levels, immune function), and protocol feasibility (eligibility criteria, protocol deviations, blinding). DISCUSSION: Despite significant observational literature suggesting VDD to be a modifiable risk factor in the PICU setting, there is no robust clinical trial evidence evaluating the benefits of rapid normalization. This phase II clinical trial will evaluate an innovative weight-based dosing regimen intended to rapidly and safely normalize vitamin D levels in critically ill children. Study findings will be used to inform the design of a multicenter phase III trial evaluating the clinical and economic benefits to rapid normalization. Recruitment for this trial was initiated in January 2016 and is expected to continue until November 30, 2017. TRIAL REGISTRATION: Clinicaltrials.gov NCT02452762.

Vitamin D in incident nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study.

BACKGROUND: Cross-sectional studies of children with prevalent nephrotic syndrome (NS) have shown 25-vitamin D (25(OH)D) deficiency rates of 20-100 %. Information on 25(OH)D status in incident patients or following remission is limited. This study aimed to assess 25(OH)D status of incident idiopathic NS children at presentation and longitudinally with short-term observation. METHODS: Multicenter longitudinal study of children (2-18 years old) from 14 centers across the Midwest Pediatric Nephrology Consortium with incident idiopathic NS. 25(OH)D levels were assessed at diagnosis and 3 months later. RESULTS: Sixty-one children, median age 5 (3, 11) years, completed baseline visit and 51 completed second visit labs. All 61 (100 %) had 25(OH)D < 20 ng/ml at diagnosis. Twenty-seven (53 %) had 25(OH)D < 20 ng/ml at follow-up. Fourteen (28 %) children were steroid resistant. Univariate analysis showed that children prescribed vitamin D supplements were less likely to have 25(OH)D deficiency at follow-up (OR 0.2, 95 % CI 0.04, 0.6). Steroid response, age, and season did not predict 25(OH)D deficiency. Multivariable linear regression modeling showed higher 25(OH)D levels at follow-up by 13.2 ng/ml (SE 4.6, p < 0.01) in children supplemented with vitamin D. CONCLUSIONS: In this incident idiopathic NS cohort, all children at diagnosis had 25(OH)D deficiency and the majority continued to have a deficiency at 2-4 months. Supplemental vitamin D decreased the odds of 25(OH)D deficiency at follow-up, supporting a role for supplementation in incident NS.

AKI in Children Hospitalized with Nephrotic Syndrome.

BACKGROUND AND OBJECTIVES: Children with nephrotic syndrome can develop life-threatening complications, including infection and thrombosis. While AKI is associated with adverse outcomes in hospitalized children, little is known about the epidemiology of AKI in children with nephrotic syndrome. The main objectives of this study were to determine the incidence, epidemiology, and hospital outcomes associated with AKI in a modern cohort of children hospitalized with nephrotic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Records of children with nephrotic syndrome admitted to 17 pediatric nephrology centers across North America from 2010 to 2012 were reviewed. AKI was classified using the pediatric RIFLE definition. RESULTS: AKI occurred in 58.6% of 336 children and 50.9% of 615 hospitalizations (27.3% in stage R, 17.2% in stage I, and 6.3% in stage F). After adjustment for race, sex, age at admission, and clinical diagnosis, infection (odds ratio, 2.24; 95% confidence interval, 1.37 to 3.65; P=0.001), nephrotoxic medication exposure (odds ratio, 1.35; 95% confidence interval, 1.11 to 1.64; P=0.002), days of nephrotoxic medication exposure (odds ratio, 1.10; 95% confidence interval, 1.05 to 1.15; P<0.001), and intensity of medication exposure (odds ratio, 1.34; 95% confidence interval, 1.09 to 1.65; P=0.01) remained significantly associated with AKI in children with nephrotic syndrome. Nephrotoxic medication exposure was common in this population, and each additional nephrotoxic medication received during a hospitalization was associated with 38% higher risk of AKI. AKI was associated with longer hospital stay after adjustment for race, sex, age at admission, clinical diagnosis, and infection (difference, 0.45 [log]days; 95% confidence interval, 0.36 to 0.53 [log]days; P<0.001). CONCLUSIONS: AKI is common in children hospitalized with nephrotic syndrome and should be deemed the third major complication of nephrotic syndrome in children in addition to infection and venous thromboembolism. Risk factors for AKI include steroid-resistant nephrotic syndrome, infection, and nephrotoxic medication exposure. Children with AKI have longer hospital lengths of stay and increased need for intensive care unit admission.

Prevention of vitamin D deficiency in children following cardiac surgery: study protocol for a randomized controlled trial.

BACKGROUND: Vitamin D is a pleiotropic hormone important for the recovery of organ systems after critical illness. Recent observational studies have suggested that three out of every four children are vitamin D deficient following cardiac surgery, with inadequate preoperative intake and surgical losses playing important contributory roles. Observed associations between postoperative levels, cardiovascular dysfunction and clinical course suggest that perioperative optimization of vitamin D status could improve outcome. With this two-arm, parallel, double blind, randomized controlled trial (RCT), we aim to compare immediate postoperative vitamin D status in children requiring cardiopulmonary bypass for congenital heart disease who receive preoperative daily high dose vitamin D supplementation (high-dose arm) with those who receive usual intake (low-dose arm). METHODS/DESIGN: Eligibility requirements include age (>36 weeks, <18 years) and a congenital heart defect requiring cardiopulmonary bypass surgical correction. Enrollment of 62 participants will take place at a single Canadian tertiary care center over a period of 2 years. Children randomized to the high-dose group will receive age-based dosing that was informed by the Institute of Medicine (IOM) daily tolerable upper intake level (<1 year old = 1,600 IU/day, >1 year old = 2,400 IU/day). Children in the low-dose arm will receive usual care based on IOM recommendations (<1 year old = 400 IU, >1 year old = 600 IU). The primary outcome measure is immediate postoperative vitamin D status, using blood 25(OH)D. DISCUSSION: Maintaining adequate postoperative vitamin D levels following surgery could represent an effective therapy to speed recovery following CHD surgery. The proposed research project will determine whether preoperative supplementation with a dosing regimen based on the IOM recommended daily upper tolerable intake will prevent postoperative vitamin-D deficiency in the majority of children. The results will then be used to inform the design of a large international RCT exploring whether preoperative optimization of vitamin D status might improve short and long-term outcomes in this vulnerable population. TRIAL REGISTRATION: Clinicaltrials.gov Identifier--NCT01838447 Date of registration: 11 April 2013.

Resolution of refractory hypotension and anuria in a premature newborn with loss-of-function of ACE.

We present the investigation and management of a premature, hypotensive neonate born after a pregnancy complicated by anhydramnios to highlight the impact of early and informed management for rare kidney disease. Vasopressin was used to successfully treat refractory hypotension and anuria in the neonate born at 27 weeks of gestation. Next generation sequencing of a targeted panel of genes was then performed in the neonate and parents. Subsequently, two compound heterozygous deletions leading to frameshift mutations were identified in the angiotensin 1-converting enzyme gene ACE; exon 5:c.820_821delAG (p.Arg274Glyfs*117) and exon24: c.3521delG (p.Gly1174Alafs*12), consistent with a diagnosis of renal tubular dysgenesis. In light of the molecular diagnosis, identification, and treatment of associated low aldosterone level resulted in further improvement in renal function and only mild residual chronic renal failure is present at 14 months of age. Truncating alterations in ACE most often result in fetal demise during gestation or in the first days of life and typically as a result of the Potter sequence. The premature delivery, and serendipitous early treatment with vasopressin, and then later fludrocortisone, resulted in an optimal outcome in an otherwise lethal condition.

Autonomic nervous system dysregulation in pediatric hypertension.

Historically, primary hypertension (HTN) has been prevalent typically in adults. Recent data however, suggests an increasing number of children diagnosed with primary HTN, mainly in the setting of obesity. One of the factors considered in the etiology of HTN is the autonomous nervous system, namely its dysregulation. In the past, the sympathetic nervous system (SNS) was regarded as a system engaged mostly in buffering major acute changes in blood pressure (BP), in response to physical and emotional stressors. Recent evidence suggests that the SNS plays a much broader role in the regulation of BP, including the development and maintenance of sustained HTN by a chronically elevated central sympathetic tone in adults and children with central/visceral obesity. Consequently, attempts have been made to reduce the SNS hyperactivity, in order to intervene early in the course of the disease and prevent HTN-related complications later in life.

The Canadian Childhood Nephrotic Syndrome (CHILDNEPH) Project: overview of design and methods.

BACKGROUND: Nephrotic syndrome is a commonly acquired kidney disease in children that causes significant morbidity due to recurrent episodes of heavy proteinuria. The management of childhood nephrotic syndrome is known to be highly variable among physicians and care centres. OBJECTIVES: The primary objective of the study is to determine centre-, physician-, and patient-level characteristics associated with steroid exposure and length of steroid treatment. We will also determine the association of dose and duration of steroid treatment and time to first relapse as a secondary aim. An embedded qualitative study utilizing focus groups with health care providers will enrich the quantitative results by providing an understanding of the attitudes, beliefs and local contextual factors driving variation in care. DESIGN: Mixed-methods study; prospective observational cohort (quantitative component), with additional semi-structured focus groups of healthcare professionals (qualitative component). SETTING: National study, comprised of all 13 Canadian pediatric nephrology clinics. PATIENTS: 400 patients under 18 years of age to be recruited over 2.5 years. MEASUREMENTS: Steroid doses for all episodes (first presentation, first and subsequent relapses) tracked over course of the study. Physician and centre-level characteristics catalogued, with reasons for treatment preferences documented during focus groups. METHODS: All patients tracked prospectively over the course of the study, with data comprising a prospective registry. One focus group at each site to enrich understanding of variation in care. LIMITATIONS: Contamination of treatment protocols between physicians may occur as a result of concurrent focus groups. CONCLUSIONS: Quantitative and qualitative results will be integrated at end of study and will collectively inform strategies for the development and implementation of standardized evidence-based protocols across centres.

CONTEXTE: Le syndrome néphrotique est une néphropathie fréquente chez l'enfant, qui cause une morbidité considérable en raison de la récurrence d'épisodes de protéinurie importante. La gestion du syndrome néphrotique de l'enfant varie énormément d'un médecin et d'un centre de soins à l'autre. OBJECTIFS: L'objectif principal de cette étude est de déterminer les caractéristiques associées à l'exposition et la durée du traitement aux stéroïdes, liées au centre, au médecin et au patient. En deuxième lieu, nous déterminerons la corrélation entre la dose et la durée du traitement aux stéroïdes, puis la durée avant la première rechute. À cette étude s'ajoutera une étude qualitative avec des groupes de discussion composés de professionnels de la santé qui viendra enrichir les résultats quantitatifs en favorisant une meilleure compréhension des attitudes, des croyances et des facteurs contextuels locaux qui entraînent des variations dans les soins. TYPE D'ÉTUDE: Une étude méthodologique mixte; étude d'observation de cohorte prospective (composante quantitative), combinée avec des groupes de discussion semi-structurés composés de professionnels de la santé (composante qualitative). CONTEXTE/ÉCHANTILLON: Étude nationale, constituée des 13 cliniques canadiennes de néphrologie pédiatrique. PARTICIPANTS: 400 patients âgés de moins de 18 ans, à recruter sur une période de 2,5 années. MESURES: Suivi des doses de stéroïdes pour chacun des épisodes (première présentation, première rechute et suivantes), tout au long de l'étude. Catalogage des caractéristiques liées au médecin ou au centre, et attestation des raisons justifiant les préférences de traitement au cours des séances avec les groupes de discussion. MÉTHODES: Tous les patients suivis de manière prospective dans le cadre de l'étude, dont les données constituent un registre prospectif. Un groupe de discussion à chaque endroit, afin d'enrichir la compréhension des variations dans les soins. LIMITES DE L'ÉTUDE: La contamination des protocoles de traitement entre les médecins peut se produire en raison de la tenue simultanée de groupes de discussions. CONCLUSIONS: Les résultats quantitatifs et qualitatifs seront intégrés à la fin de l'étude et permettront de mettre en place des stratégies de développement et de mise en œuvre de protocoles normalisés et fondés sur des données probantes.

Pretreatment of infant formula with sodium polystyrene sulfonate : focus on optimal amount and contact time.

BACKGROUND: In pediatric patients at risk of hyperkalemia there are limited treatment or preventive alternatives for this electrolyte imbalance. Oral or rectal sodium polystyrene sulfonate (SPS) has several potential adverse effects, and dietary potassium restriction may compromise nutrition. Pretreatment of infant formula with SPS has been previously studied with promising efficacy. The optimal dosing and contact time has not been fully elucidated for this practice, nor have brand and generic products been compared. OBJECTIVE: The present study aimed to evaluate the effectiveness of varying amounts of brand and generic SPS for the removal of potassium from formula after 1 and 24 hours. METHODS: SPS was added to infant formula in four different amounts measured in milliliters to reflect how a parent or caregiver would measure this product at home. After 1 and 24 hours samples were withdrawn and potassium and sodium levels were measured. RESULTS: Potassium decreased in all samples, with the greatest reduction after the addition of 10 mL of SPS. Sodium levels increased in all pretreated samples to a greater extent than the potassium reduction. Contact time of either 1 or 24 hours did not impact the amount of potassium removed or the increase in sodium concentration. There were also no differences found between generic and brand SPS products. CONCLUSION: The effectiveness of SPS for formula pretreatment appears to have a plateau effect beyond the addition of 20 mL (16.47 g of brand name product, 19.5 g of generic product). This study demonstrates an effective protocol for pretreatment of formula.

Is cyclophosphamide effective in patients with IgM-positive minimal change disease?

BACKGROUND: We analyzed the impact of immunoglobulin M (IgM) positivity on the relapse-free interval post completed course of cyclophosphamide (CYC) treatment in patients with steroid-dependent nephrotic syndrome (SDNS) and minimal change disease (MCD). METHODS: This was a retrospective chart review of all children who received CYC for SDNS and MCD between 1988 and 2009. Patients were divided into three groups based on kidney biopsy: MCD without immunoglobulin M (IgM) positivity (IgM-), MCD with IgM-positive immunofluorescence (IF) only (IgM+), and MCD with IgM-positive IF and electron-dense deposits on electron microscopy (IgM++). The relapse-free time interval to the first relapse post-CYC therapy or up to 48 months of follow-up (if no relapse occurred) was used for survival analysis. RESULTS: Forty children aged 1.5-12.3 years (15 were IgM-, 16 were IgM+, 9 were IgM++) received a cumulative CYC dose of 175 ± 30 mg/kg. The overall relapse-free survival time was 75 % at 12 months, 64 % at 24 months, 59 % at 36 months, and 56 % at 48 months, with no significant differences between the IgM groups (p = 0.80). CONCLUSIONS: Based on our results, we conclude that more than 50% of our SDNS patients with MCD remained relapse-free 4 years post-CYC treatment. No significant difference in the response to CYC was observed between patients with or without IgM positivity.

Transient hyperphosphatasemia in pediatric renal transplant patients--is there a need for concern and when?

TH of infancy and early childhood is characterized by transiently increased S-ALP, predominantly its bone or liver isoforms. There are neither signs of metabolic bone disease or hepatopathy corresponding to the increased S-ALP, nor a common underlying/triggering disease. TH may also occur in children post-renal Tx, which may raise significant concerns and anxiety. We describe four patients aged 2.8-7 yr in whom the TH occurred at 11-34 (median = 28) months after Tx and lasted from 40 to 105 (median = 63) days. No obvious cause/trigger of TH could be found; the clinical status and bone turnover were not altered. In cases of TH post-Tx, we recommend the evaluation of basic biochemical indices and wrist X-ray. If these results are normal, TH is most likely the diagnosis and the S-ALP can be monitored over the next three months without further testing. In patients with persisting TH for more than three months and/or in children with pre-existing or suspected metabolic bone disease, further evaluation may be indicated. In conclusion, TH is a benign disorder in patients post-Tx. Detailed investigation including bone biopsy is only indicated in patients with persisting TH.

Complications of chronic kidney disease in children post-renal transplantation - a single center experience.

Similar to adults, CKD may persist after pediatric RTx. Clinical and laboratory parameters were analyzed retrospectively in 23 RTx recipients (13 males, age 11.9 +/- 5.2 yr), initially treated with prednisone, calcineurin inhibitor (TAC = 18, cyclosporine neoral = 5), and MMF at four months post-RTx (T1) and at 3.4 +/- 2.8 yr post-RTx (T2). Mean (+/-s.d.) cystatin C GFR (mL/min/1.73 m(2)) was 72 +/- 19 at T1 and 70 +/- 22 at T2 (NS). At T2, CKD stage I was present in five patients (22%), stage II in eight patients (35%), and stage III in 10 patients (43%). At T2, calcineurin inhibitors were utilized in 19, MMF in 13, and SIR in 13 patients. The prevalence of hypertension was 69% at T1 and 87% at T2 (p = NS). Anemia was diagnosed in 61% at T1 and 69% at T2 with average therapeutic MMF (2.78 +/- 1.3 mg/mL) and SIR (7.62 +/- 2.3 mg/mL) trough levels. Hypercholesterolemia was detected in 44.0% at T1 and 47% at T2. Bone disease was diagnosed in 26.0% at T1 and 21.7% at T2. Mean height Z-scores were -1.0 +/- 1.2 (T1) and -1.0 +/- 1.59 (T2, NS), with 21% at T1 and 30% at T2 below two SDS. We observed suboptimal growth, hypertension, hypercholesterolemia, bone disease, and anemia in a significant proportion of transplanted children.