Amy Staples

Risk Factors for the Hemolytic Uremic Syndrome in Children Infected with Escherichia coli O157:H7: a Multivariable Analysis

BACKGROUND Escherichia coli O157:H7 is the leading cause of hemolytic uremic syndrome (HUS). Risk factors for development of this complication warrant identification. METHODS We enrolled children infected with E. coli O157:H7 within 1 week of the onset of diarrhea in this prospective cohort study. The study was conducted in 5 states over 9.5 years . The primary and secondary outcomes were HUS (hematocrit <30% with smear evidence of hemolysis, platelet count <150 × 10(3)/µL, and serum creatinine concentration > upper limit of normal for age) and oligoanuric HUS. Univariate and multivariable and ordinal multinomial regression analyses were used to test associations between factors apparent during the first week of illness and outcomes. RESULTS Of the 259 children analyzed, 36 (14%) developed HUS. Univariate analysis demonstrated that children who received antibiotics during the diarrhea phase more frequently developed HUS than those who did not (36% vs 12%; P = .001). The higher rate of HUS was observed across all antibiotic classes used. In multivariable analysis, a higher leukocyte count (adjusted odds ratios [aOR] 1.10; 95% CI, 1.03-1.19), vomiting (aOR 3.05; 95% CI, 1.23-7.56), and exposure to antibiotics (aOR 3.62; 95% CI, 1.23-10.6) during the first week of onset of illness were each independently associated with development of HUS. Multinomial ordinal logistic regression confirmed that initial leukocyte count and antibiotic use were independently associated with HUS and, additionally, these variables were each associated with the development of oligoanuric HUS. CONCLUSIONS Antibiotic use during E. coli O157:H7 infections is associated with a higher rate of subsequent HUS and should be avoided.

Association Between Clinical Risk Factors and Progression of Chronic Kidney Disease in Children

BACKGROUND AND OBJECTIVES Children with chronic kidney disease (CKD) have an increased risk of progression to ESRD. There is a need to identify treatments to slow the progression of CKD, yet there are limited data regarding clinical risk factors that may be suitable targets to slow progression. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We performed a retrospective cohort study using the North American Pediatric Renal Trials and Cooperative Studies CKD database. There were 4166 pediatric subjects with CKD stages II to IV. Disease progression was defined as a GFR on follow-up of <15 ml/min per 1.73 m(2) or termination in the registry because of dialysis or transplantation. We used Kaplan-Meier and Cox proportional hazards methods to describe progression rates and determine factors associated with CKD progression. RESULTS In the univariate analysis, CKD progression was associated with age, gender, race, primary disease, CKD stage, registration year, hematocrit, albumin, corrected calcium, corrected phosphorus, and use of certain medications. Factors that remained significant in the multivariate analysis were age, primary disease, CKD stage, registration year, hypertension, corrected phosphorus, corrected calcium, albumin, hematocrit, and medication proxies for anemia and short stature. CONCLUSIONS There are multiple risk factors associated with disease progression in the pediatric CKD population. Factors that may be amenable to intervention include anemia, hypoalbuminemia, hyperphosphatemia, hypocalcemia, hypertension, and short stature. Because of the retrospective nature of our study, confirmation of our results from ongoing prospective studies is warranted before recommending prospective interventional trials.

Anemia and Risk of Hospitalization in Pediatric Chronic Kidney Disease

BACKGROUND AND OBJECTIVES Anemia is a well known complication of chronic kidney disease (CKD); however, the prevalence of anemia within CKD stages in the pediatric population has not been established. Additionally, the associated morbidity of anemia in the pediatric CKD population has not been elucidated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 2,779 patients ages 2 yr and older in the North American Pediatric Renal Trials and Collaborative Studies database with CKD stage II to V (excluding dialysis or previous transplant patients) were identified. Descriptive statistics and multivariate modeling using logistic regression was performed to determine the prevalence of anemia and to evaluate the correlation between baseline anemia and hospitalization. RESULTS The prevalence of anemia (hematocrit < 33%) increased from 18.5% in CKD stage II to 68% in CKD stage V (predialysis). Anemic children were 55% more likely to be hospitalized when compared with nonanemic children (odds ratio 1.55; 95% confidence interval 1.23 to 1.94). Similar results were obtained using hematocrit cutoffs of 36 and 39%. CONCLUSIONS In this pediatric predialysis CKD population, anemia increases with increasing CKD stage and is significantly associated with hospitalization risk. Hematocrit levels above 36 and 39% were not associated with increased risk of hospitalization. Further examination into the effect of correcting anemia on hospitalization rates may provide additional useful information.

Risk Factors for Progression of Chronic Kidney Disease

Purpose of review The present review provides an overview of the identified risk factors for chronic kidney disease (CKD) progression emphasizing the pediatric population. Recent findings Over the past 10 years, there have been significant changes to our understanding and study of preterminal kidney failure. Recent refinements in the measurement of glomerular filtration rate and glomerular filtration rate estimating equations are important tools for identification and association of risk factors for CKD progression in children. In pediatric CKD, lower level of kidney function at presentation, higher levels of proteinuria, and hypertension are known markers for a more rapid decline in glomerular filtration rate. Anemia and other reported risk factors from the pregenomic era require further study and validation. Genome-wide association studies have identified genetic loci that have provided novel genetic risk factors for CKD progression. Summary With cohort studies of children with CKD becoming mature, they have started to yield important refinements to the assessment of CKD progression. Although many of the traditional risk factors for renal progression will certainly be assessed, such cohorts will be important for evaluating novel risk factors identified by genome-wide studies.

Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study

Background Single-center studies suggest that neonatal acute kidney injury (AKI) is associated with poor outcomes. However, inferences regarding the association between AKI, mortality, and hospital length of stay are limited due to the small sample size of those studies. In order to determine whether neonatal AKI is independently associated with increased mortality and longer hospital stay, we analyzed the Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) database. Methods All neonates admitted to 24 participating neonatal intensive care units from four countries (Australia, Canada, India, United States) between January 1 and March 31, 2014, were screened. Of 4273 neonates screened, 2022 (47·3%) met study criteria. Exclusion criteria included: no intravenous fluids ≥48 hours, admission ≥14 days of life, congenital heart disease requiring surgical repair at <7 days of life, lethal chromosomal anomaly, death within 48 hours, inability to determine AKI status or severe congenital kidney abnormalities. AKI was defined using a standardized definition —i.e., serum creatinine rise of ≥0.3 mg/dL (26.5 mcmol/L) or ≥50% from previous lowest value, and/or if urine output was <1 mL/kg/h on postnatal days 2 to 7. Findings Incidence of AKI was 605/2022 (29·9%). Rates varied by gestational age groups (i.e., ≥22 to <29 weeks =47·9%; ≥29 to <36 weeks =18·3%; and ≥36 weeks =36·7%). Even after adjusting for multiple potential confounding factors, infants with AKI had higher mortality compared to those without AKI [(59/605 (9·7%) vs. 20/1417 (1·4%); p< 0.001; adjusted OR=4·6 (95% CI=2·5–8·3); p=<0·0001], and longer hospital stay [adjusted parameter estimate 8·8 days (95% CI=6·1–11·5); p<0·0001]. Interpretation Neonatal AKI is a common and independent risk factor for mortality and longer hospital stay. These data suggest that neonates may be impacted by AKI in a manner similar to pediatric and adult patients. Funding US National Institutes of Health, University of Alabama at Birmingham, Cincinnati Children’s, University of New Mexico.

Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates: Design of a Retrospective Cohort Study

Introduction Acute kidney injury (AKI) affects ~30% of hospitalized neonates. Critical to advancing our understanding of neonatal AKI is collaborative research among neonatologists and nephrologists. The Neonatal Kidney Collaborative (NKC) is an international, multidisciplinary group dedicated to investigating neonatal AKI. The AWAKEN study (Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates) was designed to describe the epidemiology of neonatal AKI, validate the definition of neonatal AKI, identify primary risk factors for neonatal AKI, and investigate the contribution of fluid management to AKI events and short-term outcomes. Methods and analysis The NKC was established with at least one pediatric nephrologist and neonatologist from 24 institutions in 4 countries (USA, Canada, Australia, and India). A Steering Committee and four subcommittees were created. The database subcommittee oversaw the development of the web-based database (MediData Rave™) that captured all NICU admissions from 1/1/14 to 3/31/14. Inclusion and exclusion criteria were applied to eliminate neonates with a low likelihood of AKI. Data collection included: (1) baseline demographic information; (2) daily physiologic parameters and care received during the first week of life; (3) weekly “snapshots”; (4) discharge information including growth parameters, final diagnoses, discharge medications, and need for renal replacement therapy; and (5) all serum creatinine values. Ethics and dissemination AWAKEN was proposed as human subjects research. The study design allowed for a waiver of informed consent/parental permission. NKC investigators will disseminate data through peer-reviewed publications and educational conferences. Discussion The purpose of this publication is to describe the formation of the NKC, the establishment of the AWAKEN cohort and database, future directions, and a few “lessons learned.” The AWAKEN database includes ~325 unique variables and >4 million discrete data points. AWAKEN will be the largest, most inclusive neonatal AKI study to date. In addition to validating the neonatal AKI definition and identifying risk factors for AKI, this study will uncover variations in practice patterns related to fluid provision, renal function monitoring, and involvement of pediatric nephrologists during hospitalization. The AWAKEN study will position the NKC to achieve the long-term goal of improving the lives, health, and well-being of newborns at risk for kidney disease.

The impact of fluid balance on outcomes in critically ill near-term/term neonates: a report from the AWAKEN study group

BackgroundIn sick neonates admitted to the NICU, improper fluid balance can lead to fluid overload. We report the impact of fluid balance in the first postnatal week on outcomes in critically ill near-term/term neonates.MethodsThis analysis includes infants ≥36 weeks gestational age from the Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN) study (N = 645). Fluid balance: percent weight change from birthweight. Primary outcome: mechanical ventilation (MV) on postnatal day 7.ResultsThe median peak fluid balance was 1.0% (IQR: −0.5, 4.6) and occurred on postnatal day 3 (IQR: 1, 5). Nine percent required MV at postnatal day 7. Multivariable models showed the peak fluid balance (aOR 1.12, 95%CI 1.08–1.17), lowest fluid balance in 1st postnatal week (aOR 1.14, 95%CI 1.07–1.22), fluid balance on postnatal day 7 (aOR 1.12, 95%CI 1.07–1.17), and negative fluid balance at postnatal day 7 (aOR 0.3, 95%CI 0.16–0.67) were independently associated with MV on postnatal day 7.ConclusionsWe describe the impact of fluid balance in critically ill near-term/term neonates over the first postnatal week. Higher peak fluid balance during the first postnatal week and higher fluid balance on postnatal day 7 were independently associated with MV at postnatal day 7.