The impact of fluid balance on outcomes in premature neonates: a report from the AWAKEN study group.

BACKGROUND: We evaluated the epidemiology of fluid balance (FB) over the first postnatal week and its impact on outcomes in a multi-center cohort of premature neonates from the AWAKEN study. METHODS: Retrospective analysis of infants <36 weeks' gestational age from the AWAKEN study (N = 1007). FB was defined by percentage of change from birth weight. OUTCOME: Mechanical ventilation (MV) at postnatal day 7. RESULTS: One hundred and forty-nine (14.8%) were on MV at postnatal day 7. The median peak FB was 0% (IQR: -2.9, 2) and occurred on postnatal day 2 (IQR: 1,5). Multivariable models showed that the peak FB (aOR 1.14, 95% CI 1.10-1.19), lowest FB in first postnatal week (aOR 1.12, 95% CI 1.07-1.16), and FB on postnatal day 7 (aOR 1.10, 95% CI 1.06-1.13) were independently associated with MV on postnatal day 7. In a similar analysis, a negative FB at postnatal day 7 protected against the need for MV at postnatal day 7 (aOR 0.21, 95% CI 0.12-0.35). CONCLUSIONS: Positive peak FB during the first postnatal week and more positive FB on postnatal day 7 were independently associated with MV at postnatal day 7. Those with a negative FB at postnatal day 7 were less likely to require MV.

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

BACKGROUND: In 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. METHODS: This 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. RESULTS: The 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. CONCLUSIONS: We 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.

Iohexol-measured glomerular filtration rate in children and adolescents with chronic kidney disease: a pilot study comparing venous and finger stick methods.

BACKGROUND: Measurement of glomerular filtration rate by iohexol disappearance (iGFR) has become a gold standard in the pediatric chronic kidney disease (CKD) population. The need for serial phlebotomy can be difficult and minimizing venipunctures would be beneficial. Furthermore, finger stick collection for dried blood spot (DBS) may be more tolerable in the pediatric population, and equivalence between these two methods may further simplify the process. METHODS: This was a cross-sectional study in children and adolescents 1 to 21 years with stages I-IV CKD. Iohexol was infused and blood drawn 10, 30, 120, and 300 min later. Blood spots on filter paper were collected by finger stick after each of the latter two blood draws. The rate of iohexol plasma disappearance was used to calculate GFR. Pearson's correlation coefficient and bias, Students t test, and Bland-Altman graphical representations were used to compare methods. RESULTS: Forty-one patients were recruited. The mean creatinine was 1.13 mg/dL (SD 0.45), the mean 4-point iGFR was 73.2 ml/min/1.73m2 (SD 27.5) and the mean 2-point iGFR was 75.6 ml/min/1.73m2 (SD 27.3). Correlation between 2-point and 4-point venous GFR was r = 0.97; p < 0.001. The correlation between the DBS and the 2-point venous GFR was r = 0.95; p < 0.001, with no significant bias. Ninety-four percent of the 2-point GFR's were within 10% of the 4-point GFR's and 80% of DBS-GFRs were within 10% of the 2-point GFR's. CONCLUSIONS: The 2-point iGFR was highly correlated and agreed well with the 4-point iGFR. The same was true for the DBS method and the 2-point venous method. DBS sampling by finger stick sampling at 2 time points after iohexol infusion gave an acceptably accurate measurement of GFR.

Outcomes of shared institutional review board compared with multiple individual site institutional review board models in a multisite clinical trial.

BACKGROUND: Institutional review boards play a crucial role in initiating clinical trials. Although many multicenter clinical trials use an individual institutional review board model, where each institution uses their local institutional review board, it is unknown if a shared (single institutional review board) model would reduce the time required to approve a standard institutional review board protocol. OBJECTIVE: This study aimed to compare processing times and other processing characteristics between sites using a single institutional review board model and those using their individual site institutional review board model in a multicenter clinical trial. STUDY DESIGN: This was a retrospective study of sites in an open-label, multicenter randomized control trial from 2014 to 2021. Participating sites in the multicenter Chronic Hypertension and Pregnancy trial were asked to complete a survey collecting data describing their institutional review board approval process. RESULTS: A total of 45 sites participated in the survey (7 used a shared institutional review board model and 38 used their individual institutional review board model). Most sites (86%) using the shared institutional review board model did not require a full-board institutional review board meeting before protocol approval, compared with 1 site (3%) using the individual institutional review board model (P<.001). Median total approval times (41 vs 56 days; P=.42), numbers of submission rounds (1 vs 2; P=.09), and numbers of institutional review board stipulations (1 vs 4; P=.12) were lower for the group using the shared institutional review board model than those using the individual site institutional review board model; however, these differences were not statistically significant. CONCLUSION: The findings supported the hypothesis that the shared institutional review board model for multicenter studies may be more efficient in terms of cumulative time and effort required to obtain approval of an institutional review board protocol than the individual institutional review board model. Given that these data have important implications for multicenter clinical trials, future research should evaluate these findings using larger or multiple multicenter trials.

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.

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.

Validation of the revised Schwartz estimating equation in a predominantly non-CKD population.

Recently, Schwartz et al. (J Am Soc Nephrol 20:629-637, 2009) used data from the National Institutes of Health-funded Chronic Kidney Disease in Children (CKiD) study to generate new equations for estimating the glomerular filtration rate (eGFR), including an update of the commonly used bedside equation. However, it is unclear if the equation can be generalized to a broader pediatric population. We have used the updated equation on a sample of pediatric patients with less impaired renal function to evaluate the correlation between the new Schwartz equation and measured GFR by iothalamate clearance. We retrospectively analyzed 738 iothalamate clearance tests from 503 patients with a mean serum creatinine of 0.50 mg/dl whose ages ranged from 1 to 16 years. We measured bias, precision, and accuracy and performed a Bland-Altman plot to determine the measure of agreement between the two methods. The mean GFR by iothalamate clearance was 110.6 ml/min/1.73 m(2) and by the new Schwartz estimation 104.7 ml/min/1.73 m(2). The mean difference was 5.84 ml/min/1.73 m(2) (95% CI 4.00-7.67). The newly purposed bedside Schwartz equation therefore demonstrated good agreement with the iothalamate renal clearances in our patient population and appears to be a valid bedside estimating equation for GFR in this sample of children.

Orthostatic proteinuria and the spectrum of diurnal variability of urinary protein excretion in healthy children.

The aim of this study was to characterize the 24-h and diurnal variability of urinary protein excretion and identify the prevalence of orthostatic proteinuria (OP) in healthy children. Upright, supine, and 24-h total urinary protein (UrTP) and creatinine clearance (CrCl) were measured in 91 healthy children ages 6-19 years. Urinary protein and creatinine excretions were calculated and examined by gender, age, Tanner stage, and body mass index (BMI). Orthostatic proteinuria (OP) was defined as a 24-h UrTP >100 mg/m(2) with a normal supine UrTP (<4 mg/m(2)/h). There exists a marked diurnal variability in UrTP. The upright UrTP rate was three to four-times greater than the supine rate. UrTP, adjusted for body surface area, is higher in boys than girls and increases with age and BMI. There is a similar increase in upright CrCl compared with supine. Urinary protein to creatinine ratio (UPcr) is strongly correlated with UrTP. OP is common, being found in 20% of children in this cohort, and is more common in boys and associated with age >10 years and BMI >85%. In children with OP, a first morning UPcr shows a value in the normal range, whereas a random daytime UPcr is elevated. There exists a diurnal variability in urinary protein excretion that is exaggerated in participants with OP. UPcr reliably estimates 24-h UrTP. Using current pediatric criteria, OP is very common, particularly in boys. A normal first morning UPcr ratio indicates that a child with elevated random urinary protein has OP.

What happens to reading between first and third grade? Implications for students who use AAC.

School-age students who use AAC need access to communication, reading, and writing tools that can support them to actively engage in literacy learning. They also require access to core literacy learning opportunities across grade levels that foster development of conventional literacy skills. The importance of the acquisition of conventional literacy skills for students who use AAC cannot be overemphasized. And yet, one of the critical challenges in supporting the literacy learning of students who use AAC has been a lack of knowledge about literacy curricula and supports to literacy learning for these students. Most students who use AAC do not become conventionally literate and few of those who do achieve literacy skills beyond the second grade level. This article will provide an overview of the most frequent reading instructional activities in first and third grade classrooms. To better understand the foundational experiences important to literacy learning, the results of a survey project that examined the reading activities of general education students and teachers during primary grade instruction are presented, and critical shifts in instruction that occurred between first and third grade are highlighted. The primary instructional focus of core reading activities is also examined, along with adaptations for students who use AAC.

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.

C1q nephropathy and minimal change nephrotic syndrome.

C1q nephropathy (C1qN) is an uncommon disorder seen in children and adults with nephrotic syndrome and non-specific urinary findings. It has been described with minimal change nephrotic syndrome (MCNS), focal segmental glomerulonephritis and isolated mesangial proliferative glomerulonephritis. We describe nine children with MCNS and mesangial C1q deposition. These children had a median age of 2.7 years at diagnosis (range 1.3-15 years), 56% were male and 78% were Hispanic. We compared these children to concurrent patients with nephrotic syndrome and biopsy-proven MCNS. We found that the C1qN patients were more likely than MCNS children to require chronic immunosuppression with calcineurin inhibitors or mycophenolate mofetil to maintain remission. However, all children were able to achieve and sustain clinical remission of nephrotic syndrome. Children with C1qN and minimal change histology have an increased frequency of frequently relapsing and steroid-unresponsive disease, but they can attain prolonged remission and stable renal function with calcineurin inhibitor or mycophenolate mofetil therapy.

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.