Outcomes of Prophylactic Peritoneal Dialysis Catheter Insertion in Children Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVES: The objective of this Prospective Register of Systematic Reviews (CRD42022384192) registered systematic review and meta-analysis was to determine whether prophylactic peritoneal dialysis (PD) catheter insertion at the time of pediatric cardiac surgery is associated with improved short-term outcomes. DATA SOURCES: Databases search of the MEDLINE, EMBASE, CINAHL, and Cochrane Library completed in April 2021 and updated October 2023. STUDY SELECTION: Two reviewers independently completed study selection, data extraction, and bias assessment. Inclusion criteria were randomized controlled trials (RCTs) and observational studies of children (≤ 18 yr) undergoing cardiac surgery with cardiopulmonary bypass. We evaluated use of prophylactic PD catheter versus not. DATA EXTRACTION: The primary outcome was in-hospital mortality, as well as secondary short-term outcomes. Pooled random-effect meta-analysis odds ratio with 95% CI are reported. DATA SYNTHESIS: Seventeen studies met inclusion criteria, including four RCTs. The non-PD catheter group received supportive care that included diuretics and late placement of PD catheters in the ICU. Most study populations included children younger than 1 year and weight less than 10 kg. Cardiac surgery was most commonly used for arterial switch operation. In-hospital mortality was reported in 13 studies; pooled analysis showed no association between prophylactic PD catheter placement and in-hospital mortality. There were mixed results for ICU length of stay and time to negative fluid balance, with some studies showing shortened duration associated with use of prophylactic PD catheter insertion and others showing no difference. Overall, the studies had high risk for bias, mainly due to small sample size and lack of generalizability. CONCLUSIONS: In this meta-analysis, we have failed to demonstrate an association between prophylactic PD catheter insertion in children and infants undergoing cardiac surgery and reduced in-hospital mortality. Other relevant short-term outcomes, including markers of fluid overload, require further study.

Major Adverse Kidney Events in Pediatric Continuous Kidney Replacement Therapy.

Importance: Continuous kidney replacement therapy (CKRT) is increasingly used in youths with critical illness, but little is known about longer-term outcomes, such as persistent kidney dysfunction, continued need for dialysis, or death. Objective: To characterize the incidence and risk factors, including liberation patterns, associated with major adverse kidney events 90 days after CKRT initiation (MAKE-90) in children, adolescents, and young adults. Design, Setting, and Participants: This international, multicenter cohort study was conducted among patients aged 0 to 25 years from The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry treated with CKRT for acute kidney injury or fluid overload from 2015 to 2021. Exclusion criteria were dialysis dependence, concurrent extracorporeal membrane oxygenation use, or receipt of CKRT for a different indication. Data were analyzed from May 2 to December 14, 2023. Exposure: Patient clinical characteristics and CKRT parameters were assessed. CKRT liberation was classified as successful, reinstituted, or not attempted. Successful liberation was defined as the first attempt at CKRT liberation resulting in 72 hours or more without return to dialysis within 28 days of CKRT initiation. Main Outcomes and Measures: MAKE-90, including death or persistent kidney dysfunction (dialysis dependence or ≥25% decline in estimated glomerular filtration rate from baseline), were assessed. Results: Among 969 patients treated with CKRT (529 males [54.6%]; median [IQR] age, 8.8 [1.7-15.0] years), 630 patients (65.0%) developed MAKE-90. On multivariable analysis, cardiac comorbidity (adjusted odds ratio [aOR], 1.60; 95% CI, 1.08-2.37), longer duration of intensive care unit admission before CKRT initiation (aOR for 6 days vs 1 day, 1.07; 95% CI, 1.02-1.13), and liberation pattern were associated with MAKE-90. In this analysis, patients who successfully liberated from CKRT within 28 days had lower odds of MAKE-90 compared with patients in whom liberation was attempted and failed (aOR, 0.32; 95% CI, 0.22-0.48) and patients without a liberation attempt (aOR, 0.02; 95% CI, 0.01-0.04). Conclusions and Relevance: In this study, MAKE-90 occurred in almost two-thirds of the population and patient-level risk factors associated with MAKE-90 included cardiac comorbidity, time to CKRT initiation, and liberation patterns. These findings highlight the high incidence of adverse outcomes in this population and suggest that future prospective studies are needed to better understand liberation patterns and practices.

Consensus-Based Recommendations on Priority Activities to Address Acute Kidney Injury in Children: A Modified Delphi Consensus Statement.

Importance: Increasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge. Objective: To develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy. Evidence Review: At the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations. Findings: The meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy. Conclusions and Relevance: Existing evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts.

Mutations in CLDN2 Are Not a Common Cause of Pediatric Idiopathic Hypercalciuria in Canada.

Background: Hypercalciuria is the most common risk factor for kidney stone formation, including in pediatric patients. However, the etiology is often unknown and children are frequently diagnosed with idiopathic hypercalciuria. Nearly 50% of children with hypercalciuria have a first-degree relative with kidney stones, suggesting a strong genetic basis for this disease. A failure of calcium reabsorption from the proximal nephron is implicated in the pathogenesis of hypercalciuria. Claudin-2 is a tight junction protein abundantly expressed in the proximal tubule. It confers paracellular permeability to calcium that is essential for transport across the proximal tubule where the majority of filtered calcium is reabsorbed. Objective: Our objective was to examine the frequency of coding variations in CLDN2 in a cohort of children with idiopathic hypercalciuria. Design: Mixed method including retrospective chart review and patient interview, followed by genetic sequencing. Setting: Three tertiary care centers in Canada. Patients: Children (age 1-18 years) with idiopathic hypercalciuria. Patients with other causes of hypercalciuria were excluded. Methods: Data were collected from 40 patients with idiopathic hypercalciuria. Informed consent to collect DNA was obtained from 13 patients, and the final and only coding exon of CLDN2 was sequenced. Results: The majority of patients were male, white, and had a positive family history of kidney stones. Parathyroid hormone levels were significantly lower than the reference range (P < .001). The levels of 1,25-dihydroxyvitamin D were also significantly higher in our patient cohort, relative to the reference range (P < .001). Sequence analysis of CLDN2 did not identify any coding variations. Limitations: Sequencing analysis was limited to the final coding exon and small sample size. Conclusions: CLDN2 coding variations are not a common cause of idiopathic hypercalciuria in Canadian children. Further study is needed to determine the causes of hypercalciuria in pediatric patients and develop targeted therapies.

Contexte: L'hypercalciurie est le facteur de risque le plus courant pour la formation de calculs rénaux, y compris chez les patients pédiatriques. Son étiologie est cependant souvent inconnue et les enfants sont fréquemment diagnostiqués avec une hypercalciurie idiopathique. Près de 50 % des enfants atteints d'hypercalciurie ont un parent de premier degré souffrant de calculs rénaux, ce qui suggère une importante contribution génétique à cette maladie. Une atteinte de la réabsorption du calcium au niveau du néphron proximal est impliquée dans la pathogenèse de l'hypercalciurie. La claudine-2, une protéine de jonction abondamment exprimée dans le tubule proximal, confère une perméabilité paracellulaire au calcium, laquelle est essentielle pour le transport à travers le tubule proximal, où la majorité du calcium filtré est réabsorbée. Objectif: Étudier la fréquence des variations dans le codage de CLDN2 dans une cohorte d'enfants atteints d'hypercalciurie idiopathique. Conception de l'étude: Une méthode mixte, comprenant un examen rétrospectif des dossiers médicaux et un entretien avec les patients, suivie d'un séquençage génétique. Cadre: Trois centres de soins tertiaires au Canada. Sujets: Des enfants (1 à 18 ans) atteints d'hypercalciurie idiopathique. Les patients dont l'hypercalciurie avait une autre cause ont été exclus. Méthodologie: Les données proviennent de 40 patients atteints d'hypercalciurie idiopathique. Le consentement éclairé à la collecte d'ADN a été obtenu pour treize patients. L'exon final et le seul exon codant pour CLDN2, a été séquencé. Résultats: La majorité des sujets étaient des garçons d'origine caucasienne et avaient des antécédents familiaux de calculs rénaux. Les taux d'hormone parathyroïdienne étaient significativement plus faibles que les valeurs de référence (p < 0,001). Les taux de 1,25 dihydroxyvitamine D étaient significativement plus élevés dans notre cohorte de patients, par rapport à l'intervalle de référence (p < 0,001). Le séquençage de CLDN2 n'a pas révélé de variations dans le codage. Limites: L'étude porte sur un faible échantillon de patients et le séquençage s'est limité à l'exon final du gène. Conclusion: Les mutations du gène CLDN2 ne sont pas une cause fréquente d'hypercalciurie idiopathique chez les enfants canadiens. D'autres études sont nécessaires pour préciser la ou les causes de l'hypercalciurie chez les patients pédiatriques et développer des traitements ciblés.

Rituximab Use for the Treatment of Childhood Nephrotic Syndrome by Canadian Pediatric Nephrologists: A National Survey.

Background: There is known practice variation in the treatment of frequently relapsing, steroid-dependent, and steroid-resistant nephrotic syndrome in children. Rituximab is an emerging therapy for difficult-to-treat nephrotic syndrome; however, there are no clear treatment guidelines. We therefore hypothesized that a wide variety of approaches to this therapy exist. Objective: To evaluate when and how rituximab is used for the treatment of childhood nephrotic syndrome in Canada. Design and setting: An online survey was used. Participants: Canadian pediatric nephrologists. Methods: A cross-sectional survey was distributed across Canada through the Canadian Association of Pediatric Nephrologists (CAPN) to evaluate rituximab treatment practices. Results: Of a total of 20 responses, 19 (95%) use rituximab in the treatment of nephrotic syndrome, usually as a third or fourth agent. For the number of rituximab doses, the majority (68%) uses 2 doses each time they use it. Eighteen respondents (90%) measure B cells when using this medication, mostly monthly (50%) or every 3 months (39%). Respondents were administered additional doses of rituximab prophylactically (74%) or at first relapse (47%). Long-term drug safety and drug funding were identified as the main barriers to rituximab use. Limitations: This survey represents the practice styles of physicians in a single country, and there is a nonresponse bias of 63%. Also, associations were not calculated. Conclusions: Among Canadian pediatric nephrologists, rituximab use for nephrotic syndrome appears to be increasing, but significant practice variations remain, including approaches to B-cell monitoring. It is reserved mostly for second-line and third-line use due to cost, funding issues, and residual uncertainty regarding long-term safety. Understanding these critical areas of practice uncertainty is a first step to optimize treatment of nephrotic syndrome in children.

Contexte: Des variations sont connues dans les pratiques liées au traitement du syndrome néphrotique infantile, dépendant ou résistant aux stéroïdes, à récidives fréquentes. Le rituximab constitue une nouvelle approche thérapeutique pour soigner le syndrome néphrotique difficile à traiter. Il n'existe cependant aucune directive de traitement claire dans ce contexte. Nous avons donc émis l'hypothèse qu'il existait une grande variété d'approches dans l'utilisation de ce médicament. Objectifs: Examiner les pratiques d'utilisation (quand et comment) du rituximab dans le traitement du syndrome néphrotique infantile au Canada. Cadre et type d'étude: Étude menée par sondage en ligne. Participants: Des néphrologues pédiatriques canadiens. Méthodologie: Un sondage transversal a été distribué partout au Canada par l'entremise de l'Association canadienne des néphrologues pédiatriques (ACPN) afin d'examiner les pratiques de traitement au rituximab. Résultats: Parmi les 20 néphrologues ayant répondu au sondage, 19 (95 %) utilisent le rituximab dans le traitement du syndrome néphrotique, généralement comme 3e ou 4e agent, et la majorité d'entre eux (68 %) administre deux doses à chaque utilisation. Dix-huit répondants (90 %) mesurent les lymphocytes B lorsqu'ils emploient ce médicament, principalement tous les mois (50 %) ou tous les trois mois (39 %). Certains répondants avaient administré des doses additionnelles de rituximab à des fins prophylactiques (74 %) ou lors de la première rechute (47 %). Le recours au rituximab serait principalement freiné par des enjeux liés à son innocuité à long terme et au financement des médicaments. Limitations: Ce sondage représente les pratiques des médecins d'un seul pays et comporte un biais de non-réponse de 63 %. De plus, les associations n'ont pas été calculées. Conclusion: Chez les néphrologues pédiatriques canadiens, l'utilisation du rituximab dans le traitement du syndrome néphrotique semble augmenter; bien que des variations significatives demeurent dans la pratique, notamment en ce qui concerne les approches de surveillance des lymphocytes B. Actuellement, le rituximab est surtout utilisé comme thérapie de deuxième et de troisième ligne en raison de son coût, d'enjeux liés au financement et d'une incertitude résiduelle en ce qui concerne son innocuité à long terme. La compréhension de ces zones critiques d'incertitude dans les pratiques est une première étape pour optimiser le traitement du syndrome néphrotique chez les enfants.

Characteristics Associated with Variation in Corticosteroid Exposure in Children with Steroid-Sensitive Nephrotic Syndrome: Results from a Canadian Longitudinal Study.

Background: Variation in dose and duration of corticosteroids for childhood-onset steroid-sensitive nephrotic syndrome occurs worldwide, likely reflecting the evolving evidence on optimal dosing and variable severity of the disease observed between patients. We conducted a study to determine the associations between site, physician, and patient factors, and average daily corticosteroid dose and duration of therapy. Methods: Data were derived from the Canadian Childhood Nephrotic Syndrome (CHILDNEPH) Project, an observational longitudinal study from 2013 to 2019 of children with nephrotic syndrome involving pediatric nephrologists in 11 sites across Canada. The primary outcome was average daily corticosteroid dose prescribed per episode of proteinuria, reported as mg/m2 prednisone equivalents. Secondary outcome was duration of treatment for each episode of proteinuria in days. Exposure variables were categorized into site-, physician-, and patient-level variables. Results: In total, 328 children, median age at enrollment of 4.3 years old (interquartile range [IQR], 3.6), participated and were followed for a median time of 2.62 years (IQR, 2.6). The observed variability in average daily corticosteroid dose and in duration of therapy was mostly attributed to the site where the patient was treated. Accounting for between patient, physician, and site differences, average daily corticosteroid dose decreased with increasing age (beta coefficient, -0.07; 95% confidence interval [95% CI], -0.09 to -0.05], P<0.001). African and Indigenous ethnicity was associated with longer treatment duration compared with White patients (beta coefficient: African, 42.29, 95% CI, 7.85 to 76.73, P=0.02; Indigenous, 29.65, 95% CI, 2.79 to 56.52, P=0.03). Conclusions: We found practice variation with respect to corticosteroid prescriptions across 11 Canadian sites, and that variation is mostly explained at the site level. Age and ethnicity are important factors to be considered, because they are significantly associated with the average corticosteroid dose and duration of therapy.

Post-operative fluid overload as a predictor of hospital and long-term outcomes in a pediatric heart transplant population.

BACKGROUND: Pediatric patients undergoing heart transplant have a number of factors predisposing them to become fluid-overloaded, including capillary leak syndrome. Capillary leak and FO are associated with organ injury and may influence both short- and long-term outcomes. This study aimed to 1) determine the extent, timing, and predictors of post-operative FO and 2) investigate the association of FO with clinically important outcomes. METHODS: Between 2000 and 2012, 70 children less than 6 years old had a heart transplant at our institution. This was a secondary analysis of data from an ongoing prospective cohort study. RESULTS: FO, defined as cumulative fluid balance greater than 10% of body weight in the first 5 post-operative days, occurred in 16/70 patients (23%); 7 of these had more than 20% FO. Shorter donor ischemic time and longer cardiopulmonary bypass time were independently associated with increased risk of FO. FO >20% was a statistically significant independent predictor of mortality (P = .005), ventilation time, and PICU length of stay. There was no statistically significant association between identified neurodevelopment domains and FO. CONCLUSIONS: Our single-center experience demonstrates that FO was common after pediatric heart transplant and was associated with worse clinical outcomes. FO is a potentially modifiable factor, and research is needed to better determine risk factors and whether intervention to reduce FO can improve outcomes in pediatric heart transplant patients.

Neurocognitive and functional outcomes at 5 years of age after renal transplant in early childhood.

BACKGROUND: Clinicians often use information about developmental outcomes in decision-making around offering complex, life-saving interventions in children such as dialysis and renal transplant. This information in children with end-stage renal disease (ESRD) is limited, particularly when ESRD onset is in infancy or early childhood. METHODS: Using data from an ongoing prospective, longitudinal, inception cohort study of children with renal transplant before 5 years of age, we evaluated (1) the risk of adverse neurocognitive and functional outcomes at 5 years of age and (2) predictors of developmental outcomes. RESULTS: We found evidence of neurocognitive sequelae of ESRD in very young children; however, developmental outcomes appear remarkably better when compared with findings of two or three decades ago. Less time on dialysis predicted higher developmental scores, and hemodialysis was associated with poorer developmental outcomes. CONCLUSIONS: Our data suggest that renal replacement therapies in young children are associated with acceptable developmental outcome. Programs to identify those with developmental delays and provide early intervention may allow achievement of the child's full potential.

Acute kidney injury after heart transplant in young children: risk factors and outcomes.

BACKGROUND: Critical illness following heart transplantation can include acute kidney injury (AKI). Study objectives were to define the epidemiology of, risk factors for, or impact on outcomes of AKI after pediatric heart transplant. METHODS: Using data from a prospective study of 66 young children, we evaluated: (1) post-operative AKI rate (by pediatric modified RIFLE criteria); (2) pre, intra, and early post-operative AKI risk factors using stepwise logistic regression (3) effect of AKI on short-term outcomes (ventilation and length of pediatric intensive care unit (PICU) stay) using stepwise multiple regression. RESULTS: AKI occurred in 73 % of children. Pre-transplant ventilation and higher baseline estimated creatinine clearance (eCCl) were independent risk factors for AKI. Pre-operative inotrope use was associated with reduced risk of AKI. Tacrolimus level emerged as important in multivariable risk prediction. Children with AKI had a longer duration of ventilation and length of pediatric intensive care unit (PICU) stay, with AKI being an independent predictor. CONCLUSIONS: AKI was common after heart transplant and associated with more complicated early post-transplant course. Lower baseline eCCl was associated with lower incidence of AKI; this merits further investigation. The association of pre-operative inotropes with less AKI may reflect a pathophysiological mechanism or be a surrogate for clinical factors and management prior to transplant. Avoiding high tacrolimus levels may be a modifiable risk factor for AKI.

Establishing a Canadian national clinical trials network for kidney disease: proceedings of a planning workshop.

Knowledge generation through randomized controlled trials (RCTs) is critical to advance the medical evidence base, inform decision-making, and improve care and outcomes. Unfortunately, nephrology has typically lagged behind other medical specialties in this regard. The establishment of formal clinical trial networks can facilitate the successful conduct of RCTs and has significantly increased the number of RCTs performed worldwide in other medical specialties. No such formal network of nephrology trialists exists in Canada. On April 24, 2014, the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) Clinical Trials Committee held a stakeholder engagement meeting to address this gap and improve the nephrology clinical trial landscape in Canada. The meeting was held in Vancouver in association with the 2014 Canadian Society of Nephrology Annual General Meeting and was co-sponsored by the Kidney Foundation of Canada and CANN-NET. Attendees included nephrologists from university- and non-university-affiliated nephrology practices, administrators, and representatives from the Kidney Foundation of Canada. Through structured presentations and facilitated group discussions, the group explored the extent to which nephrology trials are currently happening in Canada, barriers to leading or participating in larger investigator-initiated trials, and strategies to improve clinical trial output in nephrology in Canada. The themes and action items arising from this meeting are discussed.

La création d'un bagage de connaissances commun par la conduite d'essais cliniques est essentielle pour assurer l'avancement des notions de base en médecine, étayer la prise de décisions, améliorer les soins aux patients et assurer de meilleurs résultats cliniques. L'établissement d'un réseau officiel et reconnu de partage des connaissances issues d'essais cliniques peut en faciliter la conduite et assurer leur bon déroulement. La preuve en est faite par l'augmentation du nombre d'essais cliniques probants ayant été menés à travers le monde, dans d'autres disciplines médicales. Malheureusement, la néphrologie tire de l'arrière à cet égard par rapport aux autres spécialités, un tel réseau de partage n'existe pas dans le domaine au Canada. C'est dans ce contexte que le 24 avril 2014, le comité des essais cliniques de la « Canadian Kidney Knowledge Translation and Generation Network ¼ (CANN-NET) a tenu une assemblée générale afin de mobiliser les parties intéressées. On a voulu leur exposer cette lacune, tenter d'apporter des solutions et ultimement, faire progresser le bilan de la néphrologie en cette matière. La conférence, en collaboration avec l'assemblée générale annuelle de la Société canadienne de néphrologie, s'est tenue à Vancouver et était subventionnée conjointement par la Fondation canadienne du Rein et le CANN-NET. Parmi les participants, on comptait des néphrologues pratiquants associés ou non à un établissement universitaire ainsi que des administrateurs et des représentants de la Fondation canadienne du Rein. À l'aide de présentations structurées et de discussions de groupe, les participants ont pu observer l'état actuel des essais cliniques au pays, identifier les barrières entravant la participation à plus grande échelle à des essais entrepris sous l'initiative d'un chercheur, et discuter de stratégies pour améliorer les résultats d'essais cliniques en néphrologie au Canada. Le présent article fait état des thèmes abordés lors de cette assemblée et des mesures à prendre pour atteindre les objectifs fixés.

Substantial practice variation exists in the management of childhood nephrotic syndrome.

BACKGROUND: Practice variation is common for nephrotic syndrome (NS) treatment. METHODS: A cross-sectional, web-based survey on NS treatment was administered to 58 Canadian pediatric nephrologists with the aim to document existing practice variation and compare practice with the recommendations of the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for NS. RESULTS: Of the 58 nephrologists asked to participate in the survey, 40 (69 %) responded. Among these, 62 % prescribed initial daily glucocorticoid (GC) therapy for 6 weeks, 26 % for 4 weeks by 26 %, and 10 % prescribed 'other'. Alternate-day GC was continued for 6 weeks by 63 % of respondents and for >6 and <6 weeks by 32 and 6 %, respectively. For biopsy-confirmed minimal change disease, 65 and 46 % of respondents chose oral cyclophosphamide for frequently relapsing and steroid-dependent phenotypes, respectively; calcineurin inhibitors or mycophenolate were the second most popular choices. Kidney biopsy was 'always' performed by 16, 39, and 97 % of respondents for frequently relapsing, steroid-dependent, and steroid-resistant patients, respectively. Rituximab had been administered by 60 % of respondents; 22, 56, and 72 % reported that they would consider rituximab for frequently relapsing, steroid-dependent, and steroid-resistant patients, respectively. Most notable differences between practice and Guideline recommendations were first presentation GC duration, GC-sparing agent choices in frequently relapsing and steroid-dependent patients, and biopsy practices. CONCLUSIONS: There is substantial Canadian practice variation in NS treatment. Assessment of factors driving variation and strategies to implement Guideline recommendations are needed.

Peri-operative interventions, but not inflammatory mediators, increase risk of acute kidney injury after cardiac surgery: a prospective cohort study.

PURPOSE: Cardiopulmonary bypass (CPB)-related inflammatory response might be one mechanism by which cardiac surgery associated acute kidney injury (CS-AKI) occurs. Interventions that may attenuate inflammation, including glucocorticoids or phosphodiesterase inhibitors, could therefore have a role in its prevention. We aimed to determine the role of inflammatory mediators in CS-AKI in children and the efficacy of commonly used peri-operative interventions to reduce CS-AKI risk. METHODS: We prospectively studied 109 children undergoing heart surgery. Using regression modeling (adjusting for covariates), we (1) evaluated the association between inflammatory mediators [interleukin (IL)-6, IL-8, C-reactive protein, and tumor necrosis factor-α levels] and CS-AKI, and (2) evaluated risk/prevention factors for CS-AKI including glucocorticoid and milrinone administration. CS-AKI was defined based on pRIFLE methods. RESULTS: CS-AKI occurred in 68% of children. No inflammatory mediator measured had an independent association with CS-AKI. Higher pre-operative glomerular filtration rate (GFR), sustained decrease in mean arterial pressure during CPB, post-operative single ventricle physiology, deep hypothermic circulatory arrest, and milrinone use at 24 h post-operatively were significant independent predictors of CS-AKI. Intra-operative steroid administration had no effect on the rate of CS-AKI. CONCLUSIONS: Although inflammatory mediators are up-regulated following CPB, we found no association between levels of inflammatory cytokines and CS-AKI. CS-AKI has complex pathophysiology and the observation that milrinone was associated with increased AKI risk (and that higher GFR predicts more injury) suggests that mechanisms beyond inflammation play a significant role. Intra-operative administration of glucocorticoid does not appear to be an effective intervention for reducing the risk of CS-AKI.

Risk factors for and outcomes of acute kidney injury in neonates undergoing complex cardiac surgery.

OBJECTIVE: To characterize the epidemiology of and identify risk factors for neonatal cardiac surgery-associated acute kidney injury (CS-AKI) and determine its impact on clinical outcomes. STUDY DESIGN: Using secondary analysis of data from an ongoing multiprovincial prospective cohort study, we studied 264 neonates undergoing complex cardiac repair. CS-AKI was defined based on the Acute Kidney Injury Network (AKIN) definition. We used regression modeling and survival analysis (adjusting for covariates) to evaluate associations. RESULTS: CS-AKI occurred in 64% of the neonates in our study cohort. Lower age, longer cardiopulmonary bypass time, hypothermic circulatory arrest, type of repair, lower preoperative serum creatinine (SCr) level, lower gestational age, and preoperative ventilation were independent risk factors for developing CS-AKI. Neonates with CS-AKI had longer times to extubation, intensive care discharge, and hospital discharge, after adjusting for covariates. Mortality was significantly increased in neonates with AKIN stage 2 or higher CS-AKI. The neonates with CS-AKI had a lower z-score for height at 2-year follow-up and were seen by more specialists. CONCLUSION: Neonatal CS-AKI is common and independently predicts important clinical outcomes, including mortality. Many risk factors are similar to those in older children, but some are unique to neonates. The observation that lower baseline SCr predicts CS-AKI merits further study. The AKIN definition, based on preoperative SCr value, is a reasonable method for defining CS-AKI in neonates. Many previous studies of CS-AKI have excluded neonates; we suggest that future intervention studies on approaches to reducing CS-AKI incidence and improving outcomes should include neonates.

Quality of life in children with vesicoureteral reflux.

Vesicoureteral reflux (VUR) is commonly diagnosed in children presenting with urinary tract infections. Antibiotic prophylaxis and ureteric surgery are standard treatments for these children. Our aim was to investigate whether health-related quality of life (HRQOL) was altered in children treated for VUR. Children aged 1-5 years with grade III or higher VUR were identified through electronic records at the Stollery Children's Hospital. Parents of these children were mailed the TNO-AZL Netherlands Organisation for Applied Scientific Research Academic Medical Centre Quality of Life (TAPQOL) questionnaire. QOL scores for this group were compared with normative controls from the instrument's creators using the Mann-Whitney U test. Thirty-two of the 96 (33%) mailed surveys were returned. Eight children had surgery, and 19 were treated with antibiotic prophylaxis. When comparing the VUR group with the control group, we found that anxiety and social functioning scores were significantly better in patients with VUR (p < 0.01). The VUR group had worse scores in problem behavior, stomach complaints ,and communication (p < 0.01). This study reveals that children with VUR have a reasonable QOL when compared with controls. However, the diagnosis of VUR and its management does have an impact on gastrointestinal complaints, behavior, and communication, which may occur as a result of chronic medical intervention.