BackgroundSingle-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.MethodsAll 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.FindingsIncidence 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].InterpretationNeonatal 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.FundingUS National Institutes of Health, University of Alabama at Birmingham, Cincinnati Children’s, University of New Mexico.

This 4‐week randomized, double blind, placebo‐controlled study (N=240), 1‐year open label trial (N=233), and single‐dose pharmacokinetic study (N=22) evaluated candesartan cilexetil (3 doses) in hypertensive children aged 6 to 17 years. Seventy‐one percent were 12 years of age or older, 71% were male, and 47% were black. Systolic (SBP)/diastolic (DBP) blood pressure declined 8.6/4.8–11.2/8.0 mm Hg with candesartan and 3.7/1.8 mm Hg with placebo (P<.01 compared to placebo for SBP and for the mid and high doses for DBP; placebo‐corrected 4.9/3.0–7.5/6.2 mm Hg). The slopes for dose were not, however, different from zero (P>.05). The response rate (SBP and DBP <95th percentile) after 1 year was 53%. The pharmacokinetic profiles in 6‐ to 12‐ and 12‐ to 17‐year‐olds were similar and were comparable to adults. Eight candesartan patients discontinued treatment because of an adverse event. Candesartan is an effective, well‐tolerated antihypertensive agent for children aged 6 to 17 years and has a pharmacokinetic profile that is similar to that in adults.

In adult patients with CKD, hypertension is linked to the development of left ventricular hypertrophy, but whether this association exists in children with CKD has not been determined conclusively. To assess the relationship between BP and left ventricular hypertrophy, we prospectively analyzed data from the Chronic Kidney Disease in Children cohort. In total, 478 subjects were enrolled, and 435, 321, and 142 subjects remained enrolled at years 1, 3, and 5, respectively. Echocardiograms were obtained 1 year after study entry and then every 2 years; BP was measured annually. A linear mixed model was used to assess the effect of BP on left ventricular mass index, which was measured at three different visits, and a mixed logistic model was used to assess left ventricular hypertrophy. These models were part of a joint longitudinal and survival model to adjust for informative dropout. Predictors of left ventricular mass index included systolic BP, anemia, and use of antihypertensive medications other than angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Predictors of left ventricular hypertrophy included systolic BP, female sex, anemia, and use of other antihypertensive medications. Over 4 years, the adjusted prevalence of left ventricular hypertrophy decreased from 15.3% to 12.6% in a systolic BP model and from 15.1% to 12.6% in a diastolic BP model. These results indicate that a decline in BP may predict a decline in left ventricular hypertrophy in children with CKD and suggest additional factors that warrant additional investigation as predictors of left ventricular hypertrophy in these patients.

Purpose To describe the prevalence and pattern of dyslipidemia in children with chronic kidney disease (CKD). Methods 391 children aged 1–16 yrs underwent measurement of serum triglyceride (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C). GFR by plasma disappearance of iohexol and urine protein/creatinine ratio (Up/c) were concomitantly measured. Multivariate analysis adjusted for age, gender, body mass index (BMI), GFR, and Up/c. Results The median GFR and age were 43 ml/min/1.73m2 and 12 years. Proteinuria was nephrotic range (Up/c > 2) in 12% and BMI exceeded the 95th percentile in 15%. 32% of the cohort had TG > 130 mg/dL. 21% had HDL-C < 40 mg/dl, and 16% had non-HDL-C > 160 mg/dL. Lower GFR was associated with higher TG, lower HDL-C and higher non-HDL-C. Overall, 45% of the cohort had dyslipidemia, defined as one or more abnormal lipid measure; 45% of those had combined dyslipidemia. Nephrotic range proteinuria was associated with dyslipidemia and combined dyslipidemia to an equal and large degree: odds ratio (OR) of 4.16 (95% CI: 1.96, 8.79). Compared to children with GFR > 50 ml/min/1.73m2, children with GFR < 30 ml/min/1.73m2 had an OR of 2.9 (95% CI: 1.47, 5.70) for any dyslipidemia and an OR of 8.58 (95% CI: 3.70, 19.88) for combined dyslipidemia. Conclusions Among children with moderate CKD, dyslipidemia is common and is associated with lower GFR, nephrotic proteinuria, and non-renal factors including age and obesity.

Objective To compare neurocognitive test performance of children with primary hypertension to that of normotensive controls. Study design Seventy-five children (10-18 years of age) with newly diagnosed, untreated hypertension and 75 frequency matched normotensive controls had baseline neurocognitive testing as part of a prospective multicenter study of cognition in primary hypertension. Subjects completed tests of general intelligence, attention, memory, executive function, and processing speed. Parents completed rating scales of executive function and the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire (PSQ-SRBD). Results Hypertension and control groups did not differ significantly in age, sex, maternal education, income, race, ethnicity, obesity, anxiety, depression, cholesterol, glucose, insulin, and C-reactive protein. Subjects with hypertension had higher PSQ-SRBD scores (p = 0.04) and triglycerides (p = 0.037). Multivariate analyses showed that hypertension was independently associated with worse performance on the Rey Auditory Verbal Learning Test (List A Trial 1, p = 0.034; List A Total, p = 0.009; Short delay recall, p = 0.013), CogState Groton Maze Learning Test delayed recall (p = 0.002), Grooved Pegboard dominant hand (p = 0.045), and Wechsler Abbreviated Scales of Intelligence Vocabulary (p = 0.016). Results indicated a significant interaction between disordered sleep (PSQ-SRBD score) and hypertension on ratings of executive function (p = 0.04), such that hypertension heightened the association between increased disordered sleep and worse executive function. Conclusions Youth with primary hypertension demonstrated significantly lower performance on neurocognitive testing compared with normotensive controls, in particular, on measures of memory, attention, and executive functions.

Children with DS have significantly increased risks of RUTAs.

Objective To assess depression in children with chronic kidney disease (CKD) and to determine associations with patient characteristics, intellectual and educational levels, and health related quality of life (HRQoL). Study design Subjects aged 6–17 years from the Chronic Kidney Disease in Children cohort study completed the Children’s Depression Inventory (CDI), Wechsler’s Abbreviated Scales of Intelligence, Wechsler Individual Achievement Test-II-Abbreviated, and the Pediatric Inventory of Quality of Life Core Scales 4.0. Regression analyses determined associations of CDI score and depression status with subject characteristics, intellectual and educational levels, and HRQoL. A joint linear mixed model and Weibull model were used to determine the effects of CDI score on longitudinal changes in glomerular filtration rate (GFR) and time to renal replacement therapy. Results 344 subjects completed the CDI. Eighteen (5%) had elevated depressive symptoms and another 7 (2%) were being treated for depression. In adjusted analyses, maternal education beyond high school was associated with 5% lower CDI scores (estimate 0.95; 95% CI 0.92, 0.99). Depression status was associated with lower IQ (99 versus 88, P= 0.053), lower achievement (95 versus 77.5, P<0.05), and lower HRQoL by parent and child reports (effect estimates −15.48; 95% CI −28.71, −2.24 and −18.39; 95% CI −27.81, −8.96, respectively). CDI score was not related to change in GFR. Conclusion Children with depression had lower psychoeducational skills and worse HRQoL. Identifying and treating depression should be evaluated as a means to improve the academic performance and HRQoL of children with CKD.

Objective To compare the reliability of blood pressure (BP) readings obtained by an oscillometric device to those obtained by auscultation and assess for differences in BP status classification based upon the two techniques. Study design Resting BP was measured by auscultation and with an oscillometric device at the same encounter in 235 subjects enrolled in the Chronic Kidney Disease in Children study. Resting auscultatory BP’s were averaged and compared with averaged oscillometric readings. BP agreement by the two methods was assessed using Bland-Altman plots, and BP status classification agreement was assessed by calculation of Kappa statistics. Results Oscillometric BP readings were higher than auscultatory readings, with a median paired difference of 9 mmHg for systolic BP (SBP) and 6 mmHg for diastolic BP (DBP). Correlation for mean SBP was 0.624 and for mean DBP was 0.491. The bias for oscillometric BP measurement was 8.7 mmHg for SBP (P<0.01) and 5.7 mmHg for DBP (P<0.01). BP status classification agreement was 61% for SBP and 63% for DBP, with Kappas of 0.31 for SBP and 0.20 for DBP. Conclusions Compared with auscultation, the oscillometric device significantly overestimated both systolic and diastolic BP, leading to frequent misclassification of BP status.