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Despite improvements in survival of premature infants, many have comorbid conditions. The role of the kidney in multiorgan dysfunction is unclear, particularly in regard to intraventricular hemorrhage (IVH). We hypothesized that infants diagnosed with acute kidney injury (AKI) have an increased risk of IVH independent of gestational age (GA) and other variables associated with both comorbidities. This prospective cohort study consisted of 125 infants with a birth weight ≤1,200 g and/or GA ≤31 weeks. A definition of AKI was used from KDIGO, not including urine output as nonoliguria is common in this population. IVH was based on serial head ultrasounds. Neonates with AKI had a higher trend towards having IVH compared to those without [14/35 (40%) vs. 22/83 (26.5%), p = 0.1]. Infants with AKI were more likely to have stage 2 IVH or higher than those without AKI [12/36 (33.3%) vs. 6/82 (7.3%); p < 0.01]. AKI was associated with a 3.6-fold increased risk of a grade 2 or higher IVH [hazard ratio (HR) 3.55, 95% confidence interval (CI) 1.39-9.07] and over 4-fold increase in risk of a grade 3 or higher IVH (HR 4.34, 95% CI 1.43-13.21). While there was no association between AKI and IVH overall, those with AKI had a higher hazard ratio to develop a grade 2 or higher IVH even when controlling for birth weight, antenatal steroid use, and 5-min Apgar score. Future studies are indicated to expand sample size and to control for other clinical variables that could be associated with both AKI and IVH.

Acute kidney injury (AKI) is a serious complication, commonly occurring in the critically ill population, with devastating short- and long-term consequences. Despite standardization of the definition and staging of AKI, early recognition remains challenging given that serum creatinine level is a marker, albeit imperfect, of kidney function and not kidney injury. Furthermore, the delay in increase in serum creatinine level after loss of glomerular filtration also prevents timely detection of decreased kidney function in patients with AKI. During the past decade, numerous clinical investigations have evaluated the utility of several biomarkers in the early diagnosis and risk stratification of AKI. In 2014, the US Food and Drug Administration approved the marketing of a test based on the combination of urine concentrations of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 ([TIMP-2] × [IGFBP7]) to determine whether certain critically ill patients are at risk for developing moderate to severe AKI. The optimal role of this biomarker in the diagnosis, management, and prognosis of AKI in different clinical settings requires further clarification. In this perspective, we summarize the biological actions of these 2 cell-cycle arrest biomarkers and present important considerations regarding the clinical application, interpretation, and limitations of this novel test for the early detection of AKI.

Strategies to improve the understanding of long-term renal consequences after neonatal acute kidney injury

Perinatal asphyxia is a common neonatal problem and contributes significantly to neonatal morbidity and mortality. This study was designed to determine whether theophylline could prevent or ameliorate renal dysfunction in term neonates with perinatal asphyxia.We randomised 159 severely asphyxiated term newborns to receive a single dose of 5 mg/kg intravenous theophylline (n = 78) or a placebo (n = 81) during the first hour of life. The infant's 24-hour fluid intake, urine volume, serum creatinine, creatinine clearance and sodium excretion were recorded during days one, three and five of life, starting 12 hours after the theophylline or placebo infusion.Neonates in the theophylline group had lower serum creatinine levels (0.83 ± 0.35 versus 1.47 ± 0.61; p = 0.00) and higher endogenous creatinine clearance (32.16 ± 16.34 versus 17.73 ± 7.92; p = 0.00) than the placebo group. Severe renal dysfunction, namely acute kidney injury, was present in 36 (15%) of the neonates in the theophylline group versus 117 (48%) in the placebo group (p0.01).A single dose of intravenous theophylline administered to term neonates with perinatal asphyxia within the first hour of life significantly decreased serum creatinine levels and significantly increased creatinine clearance.

Patients with sickle cell anemia are at risk for organ damage including kidney disease. Microalbuminuria may be an early marker of disease progression. This retrospective review analyzed laboratory and clinical findings in children with sickle cell anemia according to the presence or absence of MA during well clinic sickle cell visits. Results were analyzed in sum as well as by therapeutic intervention (not on therapy,hydroxyurea therapy, or chronic transfusion therapy). Thirty two of 144(22%) children had MA, including 20 of 82 (24%) children not on a therapeutic intervention (chronic transfusion or hydroxyurea). In children not on therapy, low hemoglobin, low fetal hemoglobin and high lactate dehydrogenase were associated with MA. Frequency of positive screens for MA for the different treatment groups were: Hydroxyurea 13%; chronic transfusion 26% and children on no treatment 24%. However,the difference between the hydroxyurea group and the chronic transfusion or no treatment groups did not reach statistical significance.Increased hemoglobin and fetal hemoglobin may provide protection against kidney disease in sickle cell anemia and should be evaluated in a randomized, prospective clinical trial.

Acute kidney injury (AKI) impairs electrolyte balance, alters fluid homeostasis and decreases toxin excretion. More recent data suggest it also affects the physiology of distant organs. We performed a prospective cohort study which invloved 122 premature infants [birth weight (BW) ≤1200 g and/or gestational age (GA)

Kidney failure or ESRD affects approximately 650,000 Americans, whereas the number with earlier stages of CKD is much higher. Although CKD and ESRD are usually associated with adulthood, it is likely that the initial stages of CKD begin early in life. Many of these pathways are associated with low birth weight and disadvantaged socioeconomic status (SES) in childhood, translating childhood risk into later-life CKD and kidney failure. Social factors are thought to be fundamental causes of disease. Although the relationship between adult SES and CKD has been well established, the role of early childhood SES for CKD risk remains obscure. This review provides a rationale for examining the association between early-life SES and CKD. By collecting data on early-life SES and CKD, the interaction with other periods in the life course could also be studied, allowing for examination of whether SES trajectories (eg, poverty followed by affluence) or cumulative burden (eg, poverty at multiple time points) are more relevant to lifetime CKD risk.

Acute kidney injury (AKI) is characterized by a sudden impairment in kidney function that results in the inability to maintain adequate fluid, electrolyte, and waste product homeostasis. It is increasingly recognized as a common and significant event for newborns cared for in the neonatal intensive care unit, with important implications for treatment decisions and clinical outcomes. Indeed, AKI is associated with mortality in critically ill children [2, 86] and adults [14, 25, 52, 65, 78], even after controlling for medical comorbidities, severity of illness scores, and patient demographics. Emerging data suggest a similar association in the neonatal population as well [32, 47, 48], such that kidney injury can no longer be viewed as an incidental finding but rather an important determinant of patient outcomes.

To investigate impact of prophylactic peritoneal dialysis (PD) on clinical outcomes and inflammatory cytokines in children following cardiac surgery with cardiopulmonary bypass.Prospective before-and-after nonrandomized cohort study.Pediatric cardiovascular intensive care unit in tertiary hospital.Fifty-two consecutive neonates and infants at high risk for postoperative fluid overload following cardiopulmonary bypass. All had PD catheters placed during primary cardiac surgery.Initial 27 patients were managed with passive peritoneal drainage and diuretics (controls). Following 25 patients were started on prophylactic PD in immediate postoperative period and managed per PD protocol (+PD).Cumulative fluid balance, indices of disease severity, and clinical outcomes were prospectively collected. Plasma interleukin-6 and interleukin-8 were measured immediately before-and-after cardiopulmonary bypass and at 24 and 48 hours post-cardiopulmonary bypass.Demographics, diagnoses, and intraoperative variables were similar. Median net fluid balance was more negative in +PD at 24 hours, -24 mL/kg (interquartile range: -62, 11) vs. +18 mL/kg (interquartile range: -26, 11), P = .003, and 48 hours, -88 mL/kg (interquartile range: -132, -54) vs. -46 mL/kg (interquartile range: -84, -12), P = .004. +PD had median 55 mL/kg less fluid intake at 24 hours, P = .058. Peritoneal drain, urine, and chest tube output were comparable over first 24 hours. Mean inotrope score was lower in +PD at 24 hours. +PD had earlier sternal closure--24 hours (interquartile range: 20, 40) vs. 63 hours (interquartile range: 44, 72), P.001--and a trend toward shorter duration of mechanical ventilation--71 hours (interquartile range: 49, 135) vs. 125 hours (interquartile range: 70, 195), P = .10. +PD experienced lower serum concentrations of interleukin-6 and interleukin-8 at 24 hours.Prophylactic PD is associated with greater net negative fluid balance, decreased inotrope requirements, and lower serum concentrations of inflammatory cytokines in the early postoperative period.

• As opposed to critically ill pediatric ICU patients, in which 82% of AKI occurs in the first few days of ICU admission, incident AKI occurred throughout first 30 day post HSCT. • AKI at 30 days post-HSCT was associated with increased mortality at 100 days post-transplant (p=0.05), but not 1-year mortality. • We were not able to show a significant difference between AKI within 7 days of life and mortality. • Improved understanding of the risks of AKI, and differences in early and late AKI after HSCT needs to be explored

We hypothesized that acute kidney injury (AKI) in asphyxiated neonates treated with therapeutic hypothermia would be associated with hypoxic-ischemic lesions on brain magnetic resonance imaging (MRI).Medical records of 88 cooled neonates who had had brain MRI were reviewed. All neonates had serum creatinine assessed before the start of cooling; at 24, 48, and 72 h through cooling; and then on day 5 or 7 of life. A neonatal modification of the Kidney Disease: Improving Global Outcomes guidelines was used to classify AKI. MRI images were evaluated by a neuroradiologist masked to outcomes. Outcome of interest was abnormal brain MRI at 7-10 d of life.AKI was found in 34 (39%) of 88 neonates, with 15, 7, and 12 fulfilling criteria for stages 1, 2, and 3, respectively. Brain MRI abnormalities related to hypoxia-ischemia were present in 50 (59%) newborns. Abnormal MRI was more frequent in infants from the AKI group (AKI: 25 of 34, 73% vs. no AKI: 25 of 54, 46%; P = 0.012; odds ratio (OR) = 3.2; 95% confidence interval (CI) = 1.3-8.2). Multivariate analysis identified AKI (OR = 2.9; 95% CI = 1.1-7.6) to be independently associated with the primary outcome.AKI is independently associated with the presence of hypoxic-ischemic lesions on postcooling brain MRI.

Several potential risk factors are being evaluated for their impact on the development of chronic kidney disease (CKD) in patients with Sickle Cell Disease (SCD). Recent studies in animals, children and adults without SCD, have established that acute kidney injury (AKI) can lead to CKD, yet the risk of repeated AKI events during vaso-occlusive crisis (VOC) has not been defined in SCD. During VOC events, patients may be at risk for developing AKI due to the use of nephrotoxic pain medications, dehydration (poor concentrating ability), hemolysis, or inflammatory responses. Multiple gaps in our understanding of AKI in SCD patients need to be addressed. Methods: In order to improve our understanding of the incidence, risk factors, and outcomes associated with AKI, we conducted a two year IRB approved retrospective review of 234 episodes of ICD-10 defined VOC admitted from Children's of Alabama Pediatric Emergency Department (ED). AKI was defined by KDIGO definition of an increase in serum creatinine (SCr) by ≥ 0.3 mg/dl or 50% increase in serum creatinine from baseline. Baseline labs were defined as the most recent outpatient laboratory value and within 12 months from admission. Thirty seven admissions were excluded as their baseline SCr could not be established. Variables analyzed included age, gender, SCD genotype, baseline and admission CBC (hemoglobin (Hb) value, white blood cell count (WBC), absolute neutrophil count (ANC), platelet count, and absolute reticulocyte count (ARC)), length of stay (LOS), and SCD modifying therapy. Generalized mixed effects model for binary outcome with random intercept, to accommodate repeated hospitalizations for the same subject, was fitted to assess the associations between clinical variables and AKI for all patients and severe phenotypes. Similarly, a generalized mixed Poisson effects model with random intercept was fitted to determine if AKI was independently associated with hospital length of stay. Results: Among 197 admissions for VOC, 33 (17%) were identified with AKI. Seventeen (52%) of the thirty three AKI events were first diagnosed in the ED. Compared to children without AKI, patients with AKI had a larger drop in hemoglobin from baseline at admission (0.5 vs. 1.21g/dL, p=0.005). For every 1 unit drop in Hb from baseline to admission, the odds of AKI increased by 49% (OR= 1.49, 95% CI 1.1-2.0). We identified no differences in AKI vs. no AKI by age, gender, SCD genotype, or SCD modifying therapy, change in WBC, ANC, Platelets or absolute reticulocyte count. In multivariate analysis accounting for age, gender, change in blood counts, SCD genotype or therapy, a drop in Hb remained the only significant variable (OR= 1.48, 95% CI 1.05-2.1). Patients with AKI admitted for vaso-occlusive crisis required significantly longer length of stay. The average LOS for those with AKI was 32% longer than the without AKI (OR 1.32, 95% CI 1.10-1.58). Conclusion: Seventeen percent of SCD patients with pain admitted to the hospital can present with or develop AKI. An acute drop in hemoglobin is a major risk factor for developing AKI. Patients that develop AKI require longer hospitalizations for their pain crisis, independent of potential confounders. Research should focus on pathophysiology of kidney injury in patients with SCD, the impact of nephrotoxic medications, and the role by which AKI leads to CKD in this population. Disclosures Askenazi: AKI foundation: Consultancy, Speakers Bureau; BTG: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau; Baxter: Consultancy, Speakers Bureau. Lebensburger:American Society of Hematology, Scholar Award: Research Funding; National Institutes of Health: Research Funding.

To report circuit characteristics and survival analysis in children weighing ≤10 kg enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry.We conducted prospective cohort analysis of the ppCRRT Registry to: (1) evaluate survival differences in children ≤10 kg compared with other children; (2) determine demographic and clinical differences between surviving and non-surviving children ≤10 kg; and (3) describe continuous renal replacement therapy (CRRT) circuit characteristics differences in children ≤5 kg versus 5-10 kg.The ppCRRT enrolled 84 children ≤10 kg between January 2001 and August 2005 from 13 US tertiary centers. Children ≤10 kg had lower survival rates than children10 kg (36/84 [43%] versus 166/260 [64%]; P .001). In children ≤10 kg, survivors were more likely to have fewer days in intensive care unit prior to CRRT, lower Pediatric Risk of Mortality 2 scores at intensive care unit admission and lower mean airway pressure (P(aw)), higher urine output, and lower percent fluid overload (FO) at CRRT initiation. Adjusted regression analysis revealed that Pediatric Risk of Mortality 2 scores, FO, and decreased urine output were associated with mortality. Compared with circuits from children 5-10 kg at CRRT initiation, circuits from children ≤5 kg more commonly used blood priming for initiation, heparin anticoagulation, and higher blood flows/effluent flows for body weight.Mortality is more common in children who are ≤10 kg at the time of CRRT initiation. Like other CRRT populations, urine output and FO at CRRT initiation are independently associated with mortality. CRRT prescription differs in small children.

Acute kidney injury (AKI) is common and portends mortality in several neonatal cohorts. Fluid overload is independently associated with poor outcomes in children and adults but has not been extensively studied in neonates. Between February 2010 and May 2011, we followed 58 neonates who met the following criteria: birth weight >2,000 g, gestational age ≥34 weeks, 5-min Apgar ≤7, and parental consent. Serum creatinine (SCr) was measured daily for first 4 days of life. AKI was defined as a rise in SCr of > 0.3 mg/dl or persistent SCr above 1.5 mg/dl. AKI was present in 9/58 (15.6 %) neonates and was associated with higher birth weight, being male, lower 5-min Apgar scores, lower cord pH, delivery room intubation, and absence of maternal pre-eclampsia. Percent weight accumulation at day 3 of life was higher in those with AKI [median = 8.2, interquartile range (IQR) = 4.4–21.6)] than without AKI (median = −4 (IQR = −6.5 to 0.0) (p

To test the hypothesis that acute kidney injury (AKI) would be independently associated with increased morbidity and mortality.A total of 96 consecutively cooled infants were reviewed retrospectively. Modified Acute Kidney Injury Network criteria were used to classify AKI based on absolute rise in serum creatinine (SCr) level from a previous trough (stage I, rise in SCr of 0.3 mg/dL or SCr 150-200%; stage II, rise in SCr of 200-300%; stage III, rise in SCr of ≥300%, SCr 2.5 mg/dL, or dialysis). Outcomes were mortality, duration of neonatal intensive care unit (NICU) stay, and duration of mechanical ventilation.AKI occurred in 36 of 96 infants (38%). Overall mortality was 7% and was higher for those with AKI, with the difference approaching statistical significance (14% vs 3% in those without AKI; P = .099). Patients with AKI stayed longer in the NICU (mean, 15.4 ± 9.3 days vs 11 ± 5.9 days; P = .014) and required prolonged mechanical ventilation (mean, 9.7 ± 5.9 days vs 4.8 ± 3.7 days; P .001). On multivariate analysis, AKI remained predictive of prolonged duration of mechanical ventilation and prolonged NICU stay.We used the Acute Kidney Injury Network definition for AKI in asphyxiated newborns undergoing therapeutic hypothermia to demonstrate that the incidence of AKI remains high, but lower than rates published before the advent of therapeutic hypothermia. We highlight the importance of recognizing AKI in asphyxiated newborns undergoing therapeutic hypothermia, along with the potential benefits of early recognition.

Summary Extracorporeal membrane oxygenation (ECMO) is a lifesaving procedure used in neonates, children, and adults with severe, reversible, cardiopulmonary failure. On the basis of single-center studies, the incidence of AKI occurs in 70%–85% of ECMO patients. Those with AKI and those who require renal replacement therapy (RRT) are at high risk for mortality, independent of potentially confounding variables. Fluid overload is common in ECMO patients, and is one of the main indications for RRT. RRT to maintain fluid balance and metabolic control is common in some but not all centers. RRT on ECMO can be performed via an in-line hemofilter or by incorporating a standard continuous renal replacement machine into the ECMO circuit. Both of these methods require specific technical considerations to provide safe and effective RRT. This review summarizes available epidemiologic data and how they apply to our understanding of AKI pathophysiology during ECMO, identifies indications for RRT while on ECMO, reviews technical elements for RRT application in the setting of ECMO, and finally identifies specific research-focused questions that need to be addressed to improve outcomes in this at-risk population.

Acute kidney injury (AKI) is a common event in several neonatal populations, and those neonates with AKI have poor outcomes. Serum creatinine (SCr)-based definitions of AKI are not ideal and are additionally limited in neonates whose SCr reflects the maternal creatinine level at birth and normally drops over the first weeks of life dependent on gestational age. Recent studies show that urine and serum biomarkers may provide a better basis than SCr on which to diagnose AKI. In this month's issue of Pediatric Nephrology, Sarafidis et al. show that urine neutrophil gelatinase-associated lipocalin (uNGAL), serum NGAL (sNGAL), and urine cystatin c (uCysC) are highest in those neonates with asphyxia who have elevated SCr. Furthermore, those with asphyxia without a concomitant rise in SCr levels have elevated levels of biomarkers compared to controls, suggesting a dose response. Once the SCr level returns to normal, the levels of novel AKI biomarkers continue to be elevated. While these findings strengthen the argument for the clinical use of these AKI biomarkers, further work is needed before they can be implemented in clinical practice. Large-scale observational multi-center studies are needed to test these biomarkers against hard clinical endpoints. In addition, randomized intervention trials which use biomarkers to define AKI need to be performed.

Acute kidney injury (AKI) is associated with increased risk of morbidity and mortality in critically ill children and adults. Neonates remain an understudied group, although previous evidence suggests that this association holds true for them as well.Attention to the issue of neonatal AKI is increasing. New studies in very low-birthweight infants, infants with congenital heart disease who undergo cardiopulmonary bypass, those who receive extracorporeal membrane oxygenation and infants with perinatal depression continue to demonstrate that AKI is common in neonates and associated with increased risk of morbidity and mortality. Additional advances in the field of neonatal AKI include adaptation of modern, categorical AKI definitions, as well as further evaluation of novel urinary biomarkers (e.g., neutrophil gelatinase-associated lipocalin) in this patient group.AKI is an independent risk factor for poor outcomes in critically ill neonates. Our ability to improve outcomes for these patients depends on heightened awareness of this issue both at the bedside as well as in research, commitment to using standardized AKI definitions in order to pool and compare data more effectively and improvement in our diagnostic methods with better AKI biomarkers so that we can identify AKI and intervene much earlier in the disease course.

• Acute kidney injury (AKI) is common in critically ill neonates. AKI affects survival, hospital expenditures, and long-term outcomes, independent of severity of illness and comorbidities. • Renal development continues until 34 weeks' gestation. Neonatal intensive care unit graduates, especially those with AKI, premature infants, and those with intrauterine growth retardation, are at risk for long-term chronic kidney disease (CKD). • Clinical sequelae of CKD include anemia, acidosis, electrolyte abnormality, growth restriction, renal osteodystrophy, fluid overload, hypertension, and uremia. Attention to these complications is critical to optimizing long-term outcomes. • Long-term survival of neonates with end-stage renal disease (ESRD) appears to be approaching that of older infants and young children, but they continue to have higher morbidity and mortality due to infectious and cardiovascular complications. • Renal replacement therapy can be performed in neonatal patients and is likely to improve outcomes in children with AKI and those with ESRD.

To test the hypothesis that noninvasive urinary biomarkers may improve early identification, differentiate causes, and predict outcomes of acute kidney injury (AKI) in very low birth weight subjects.We performed 2 nested case-control studies to compare the ability of 6 urine biomarkers to predict AKI (rise in serum creatinine of at least 0.3 mg/dL) and mortality (death before 36 weeks postmenstrual age).Compared to subjects without AKI (n = 21), those with AKI (n = 9) had higher maximum neutrophil gelatinase-associated lipocalin (OR = 1.2 [1.0, 1.6]; P.01; receiver operator characteristics [ROC] area under the curve [AUC] = .80) and higher maximum osteopontin (OR = 3.2 [1.5, 9.9]; P.01; ROC AUC = 0.83). Compared with survivors (n = 100), nonsurvivors (n = 23) had higher maximum kidney injury molecule 1 (OR = 1.1 [1.0, 1.2]; P.02; ROC AUC = 0.64) and higher maximum osteopontin (OR = 1.8 (1.2, 2.7); P.001; AUC of ROC = 0.78). The combination of biomarkers improved predictability for both AKI and mortality. Controlling for gestational age and birth weight did not affect results considerably.Urinary biomarkers can predict AKI and mortality in very low birth weight infants independent of gestational age and birth weight.

Acute kidney injury (AKI) is common in premature infants and is associated with poor outcomes. Novel biomarkers can detect AKI promptly. Because premature infants are born with underdeveloped kidneys, baseline biomarker values may differ. We describe baseline values of urinary neutrophil gelatinase associated lipocalin, (NGAL), Interleukin - 18 (IL-18), Kidney Injury Molecule -1 (KIM -1), Osteopontin (OPN), beta-2 microglobulin (B2mG) and Cystatin-C (Cys-C). Next, we test the hypothesis that these biomarkers are inversely related to gestational age (GA). Candidate markers were compared according to GA categories in 123 infants. Mixed linear regression models were performed to determine the independent association between demographics/interventions and baseline biomarker values. We found that urine NGAL, KIM-1, Cys-C and B2mG decreased with increasing GA. With correction for urine creatinine (cr), these markers and OPN/cr decreased with increasing GA. IL-18 (with or without correction for urine creatinine) did not differ across GA categories. Controlling for other potential clinical and demographic confounders with regression analysis shows that, NGAL/cr, OPN/cr and B2mG/cr are independently associated with GA. We conclude that urine values of candidate AKI biomarkers are higher in the most premature infants. These findings should be considered when designing neonatal AKI validation studies.

Acute kidney injury (AKI) independently predicts mortality in children and adults. Our understanding of the epidemiology of AKI in very LBW (VLBW) infants is limited to retrospective studies. After adjustment for demographics, comorbidities, and interventions, infants with AKI have decreased survival compared with those without AKI. The study was conducted in regional quaternary care NICU of the University of Alabama at Birmingham. VLBW infants were followed prospectively and were classified into a serum creatinine (SCr)-based classification for AKI. Forty-one of 229 (18%) VLBW infants developed AKI. Those with AKI were more likely to have umbilical artery catheters, assisted ventilation, blood pressure medications, and lower 1-and 5-min Apgar scores. Of the infants with AKI, 17 of 41 (42%) died compared with 9 of 188 (5%) of those without AKI (p < 0.001). AKI was associated with mortality with a crude hazard ratio (HR) of 9.3 (95% CI, 4.1-21.0). After adjusting for potential confounders, those with AKI had higher chance of death as the adjusted HR was 2.4 (95% CI 0.95-6.04). AKI is associated with mortality in VLBW infants. Efforts to prevent and ameliorate the impact of AKI may improve the outcomes in this vulnerable population.

Poor linear growth is a well described complication of chronic kidney disease (CKD). This study evaluated whether abnormal birth history defined by low birth weight (LBW;2500 g), prematurity (gestational age36 weeks), small for gestational age (SGA; birth weight10th percentile for gestational age), or intensive care unit (ICU) at birth were risk factors for poor growth outcomes in children with CKD.Growth outcomes were quantified by age-sex-specific height and weight z-scores during 1393 visits from 426 participants of the Chronic Kidney Disease in Children Study, an observational cohort of children with CKD. Median baseline GFR was 42.9 ml/min per 1.73 m(2), 21% had a glomerular diagnosis, and 52% had CKD for ≥ 90% of their lifetime.A high prevalence of LBW (17%), SGA (14%), prematurity (12%), and ICU after delivery (40%) was observed. Multivariate analyses demonstrated a negative effect of LBW (-0.43 ± 0.14; P0.01 for height and -0.37 ± 0.16; P = 0.02 for weight) and of SGA (-0.29 ± 0.16; P = 0.07 for height and -0.41 ± 0.19; P = 0.03 for weight) on current height and weight. In children with glomerular versus nonglomerular diagnoses, the effect of SGA (-1.08 versus -0.18; P = 0.029) on attained weight was more pronounced in children with a glomerular diagnosis.LBW and SGA are novel risk factors for short stature and lower weight percentiles in children with mild to moderate CKD independent of kidney function.

To determine the independent impact of acute kidney injury (AKI) and renal replacement therapy (RRT) in infants and children who receive extracorporeal membrane oxygenation. Despite continued expertise/technological advancement, patients who receive extracorporeal membrane oxygenation have high mortality. AKI and RRT portend poor outcomes independent of comorbidities and illness severity in several critically ill populations.Retrospective cohort study. The primary variables explored are AKI (categorical complication code for serum creatinine1.5 mg/dL or International Statistical Classification of Diseases and Related Health Problems, Revision 9 for acute renal failure), and RRT (complication/Current Procedural Terminology code for dialysis or hemofiltration). Multiple variables previously associated with mortality in this population were controlled, using logistic stepwise regression. Decision tree modeling was performed to determine optimal variables and cut points to predict mortality.Critically ill neonates (0-30 days old) and children (30 days but18 yrs old) in the Extracorporeal Life Support Organization registry.None.Neonatal mortality was 2175 (27.4%) of 7941. Nonsurvivors experienced more AKI (413 [19%] of 2175 vs. 225 [3.9%] of 5766, p.0001), and more received RRT (863 [39.7%] of 2175 vs. 923 [16.0%] of 5766, p.0001) than survivors. Pediatric mortality was 816 (41.6%) of 1962. Pediatric nonsurvivors similarly experienced more AKI (264 [32.3%] of 816 vs. 138 [12.0%] of 1146, p.0001) and RRT (487 [58.9%] of 816 vs. 353 [30.8%] of 1146, p.0001) than survivors. After adjusting for confounding variables, the adjusted odds ratio for neonatal group was 3.2 (p.0001) post AKI and 1.9 (p.0001) given RRT. Similarly, the pediatric adjusted odds ratio for mortality was 1.7 (p.001) post AKI and 2.5 (p.0001) given RRT. AKI and RRT were essential in the neonatal and pediatric mortality decision trees.After adjusting for known predictors of mortality, AKI and RRT independently predict mortality in neonates and children, who receive extracorporeal membrane oxygenation. Ascertainment of AKI risk factors, testing novel therapies, and optimizing the timing/delivery of RRT may positively impact survival.

Critically ill children with hemodynamic instability and acute kidney injury often develop fluid overload. Continuous renal replacement therapy (CRRT) has emerged as a favored modality in the management of such children. This study investigated the association between fluid overload and mortality in children receiving CRRT.Prospective observational study.297 children from 13 centers across the United States participating in the Prospective Pediatric CRRT Registry.Fluid overload from intensive care unit (ICU) admission to CRRT initiation, defined as a percentage equal to (fluid in [L] - fluid out [L])/(ICU admit weight [kg]) x 100%.The primary outcome was survival to pediatric ICU discharge. Data were collected regarding demographics, CRRT parameters, underlying disease process, and severity of illness.153 patients (51.5%) developed10% fluid overload, 51 patients (17.2%) developed 10%-20% fluid overload, and 93 patients (31.3%) developedor = 20% fluid overload. Patients who developedor = 20% fluid overload at CRRT initiation had significantly higher mortality (61/93; 65.6%) than those who had 10%-20% fluid overload (22/51; 43.1%) and those with10% fluid overload (45/153; 29.4%). The association between degree of fluid overload and mortality remained after adjusting for intergroup differences and severity of illness. The adjusted mortality OR was 1.03 (95% CI, 1.01-1.05), suggesting a 3% increase in mortality for each 1% increase in severity of fluid overload. When fluid overload was dichotomized toor = 20% and20%, patients withor = 20% fluid overload had an adjusted mortality OR of 8.5 (95% CI, 2.8-25.7).This was an observational study; interventions were not standardized. The relationship between fluid overload and mortality remains an association without definitive evidence of causality.Critically ill children who develop greater fluid overload before initiation of CRRT experience higher mortality than those with less fluid overload. Further goal-directed research is required to accurately define optimal fluid overload thresholds for initiation of CRRT.

Few published reports describe nutrition provision for critically ill children and young adults with acute kidney injury receiving continuous renal replacement therapy. The goals of this study were to describe feeding practices in pediatric continuous renal replacement therapy and to evaluate factors associated with over- and under-prescription of protein and calories.Retrospective database study.Multicenter study in pediatric critical care units.Patients with acute kidney injury (estimated glomerular filtration rate75 mL/min/1.73 m at continuous renal replacement therapy initiation) enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy Registry.None.Nutrition variables: initial and maximal protein (g/kg/day) and caloric (kcal/kg/day) prescription and predicted resting energy expenditure (kcal/kg/day). We determined factors predicting initial and maximal protein and caloric prescription by multivariate analysis.One hundred ninety-five patients (median [interquartile range] age = 8.1 [12.8] yrs, 56.9% men) were studied. Mean protein and caloric prescriptions at continuous renal replacement therapy initiation were 1.3 +/- 1.5 g/kg/day (median, 1.0; range, 0-10) and 37 +/- 27 kcal/kg/day (median, 32; range, 0-107). Mean maximal protein and caloric prescriptions during continuous renal replacement therapy were 2.0 +/- 1.5 g/kg/day (median, 1.7; range, 0-12) and 48 +/- 32 kcal/kg/day (median, 43; range, 0-117). Thirty-four percent of patients were initially prescribed1 g/kg/day protein; 23% never attained1 g/kg/day protein prescription. By continuous renal replacement therapy day 5, median protein prescribed was2 g/kg/day. Protein prescription practices differed substantially between medical centers with 5 of 10 centers achieving maximal protein prescription of2 g/kg/day inor = 40% of patients. Caloric prescription exceeded predicted resting energy expenditure by 30%-100%. Factors independently associated with maximal protein and caloric prescription while on continuous renal replacement therapy were younger age, initial protein and caloric prescription and number of continuous renal replacement therapy treatment days (p0.05).Protein prescription in pediatric continuous renal replacement therapy may be inadequate. Inter-center variation exists with respect to nutrition prescription. Feeding practice standardization and research in pediatric acute kidney injury nutrition are essential to begin providing evidence-based feeding recommendations.

The independent impact of acute kidney injury (AKI) on survival in very low birthweight (VLBW;or =1,500 g) critically ill infants has not been studied. Cases (non-survivors n = 68) were matched to, at most, two controls (survivors n = 127) by incidence density sampling with replacement, birthweight (+/- 50 g), gestational age (+/- 1 week), and availability of serum creatinine (SCr) levels before the index patient's time of death. Maternal/infant demographic characteristics, co-morbidities, complications and interventions were explored. No difference existed between patients and controls in mean gestational age and birthweight (the matching variables), race, or gender. Compared with the controls, cases had younger mothers, less placental separation, fewer occurrences of hyponatremia, more intra-ventricular hemorrhage, and received chest compressions and cardiac drugs. A 1 mg/dl increase in SCr was associated with almost two-times higher odds of death [odds ratio (OR) = 1.94, 95% confidence interval (95% CI) 1.13-3.32]. OR increased when confounding variables were adjusted (adjusted OR 3.44, 95% CI 1.23-9.61). Similarly, a 100% increase in SCr from trough level was associated with an increased OR = 1.53 (95% CI 1.14-2.04) and became stronger, after adjustment of variables (adjusted OR = 1.90, 95% CI 1.10-3.27). After confounding variables had been controlled for, AKI was independently associated with mortality in VLBW infants. Further prospective multi-center studies are needed to determine whether this association exists.

To report on the efficacy of rituximab (RTX) therapy in standard treatment-refractory, chronic Henoch-Schonlein purpura, a retrospective chart review of 3 pediatric patients treated with RTX for severe refractory chronic Henoch-Schonlein purpura was performed. All 3 patients responded to 1 or 2 courses of RTX without serious adverse events.

1Department of Pediatrics, Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama, USA; and 2Department of Pediatrics and Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA. Correspondence: D Askenazi, Department of Pediatrics, Division of Nephrology, University of Alabama at Birmingham, 1600 7th Avenue South, ACC 516, Birmingham, Alabama 35233, USA. E-mail: daskenazi@peds.uab.edu

Background: Growing evidence shows that acute kidney injury (AKI) leads to chronic kidney disease in pediatric and adult populations. Patients with sickle cell disease (SCD) that develop acute chest syndrome (ACS) are at risk for developing AKI due to the hypoxic, acidic environment in the renal medulla, the use of nephrotoxic agents (vancomycin, NSAIDs), hyposthenuria and potential dehydration experienced by patients prior to admission for ACS. As AKI and acute lung injury are linked by systemic organ cross-talk, AKI with or without oliguria, may exacerbate the pathologic state of ACS. For these reasons, improving our understanding of the epidemiology and pathophysiology of AKI during sickle cell crisis is paramount. Methods: We conducted a six year retrospective observational evaluation of 236 episodes of ICD-9 defined ACS among 166 admitted pediatric patients. We excluded patients admitted for one day or had normal CXR throughout hospitalization despite being coded as ACS. AKI was defined by KDIGO definition of either a ≥ 0.3 mg/dL or 50% increase in serum creatinine (SCr) from baseline. Forty eight episodes were excluded as a baseline SCr was not identified. Variables analyzed included age, gender, SCD genotype, length of stay, CBC (baseline and admission), current SCD therapy, transfusion intervention and length of stay (LOS). Per institutional standard of care, patients with ACS are treated with Vancomycin, Azithromycin, and Ceftriaxone and receive NSAIDS (ibuprofen or toradol) for pain/fevers but the type/timing of transfusion is determined by SCD provider preferences. Logistic regression analysis was performed to assess associations between clinical variables and AKI for all patients and severe phenotypes. Multiple linear regression analysis was performed to determine if AKI was independently associated with hospital length of stay. Results: The mean age of patients admitted with ACS was 9 years (range 0.8yrs-19) and 61% were male. Genotypes included SS (79%) SB0 thalassemia (4%), SB+ thalassemia (5%), SC (12%) and SD (1%). AKI was identified in 13 of 188 (7%) episodes of ACS. The majority of cases developed AKI within two days of admission and resolved 2.5 days later. Compared to children without AKI, those with AKI had a lower admission hemoglobin (6.3 vs 7.5 g/dL, p=0.02), lower decrease in hemoglobin from baseline (3.2 vs. 1.3 g/dL, p Conclusion: This study demonstrates that AKI is prevalent during admissions for ACS and is highly associated with a drop in Hb and increase in WBC on admission and the need for exchange transfusion. While AKI presented and resolved early during hospitalization, it is strongly associated with a prolonged hospital course. The impact of AKI on the pathophysiology of ACS in the acute setting as well as its role in progression to SCD nephropathy should be studied prospectively. Disclosures No relevant conflicts of interest to declare.

Few data exist regarding the long-term sequelae of acute renal failure (ARF), and these studies are limited to a few renal conditions. We aim to assess the 3–5-year survival and incidence of renal injury in children who previously developed ARF of varying causes. We queried parents, physicians, and hospital/state vital statistics records to find patient survival in 174 children who previously had ARF and survived to hospital discharge. We assessed the following in 29 children for residual renal injury: (a) microalbuminuria, (b) glomerular filtration rate (GFR) by Schwartz formula, (c) hypertension, and (d) hematuria. The 3–5-year survival of children with ARF who survived to hospital discharge was 139/174 (79.9%). Most deaths (24/35 (68.5%)) occurred within 12 months after initial hospitalization. Combining those who died during initial hospitalization and in subsequent 3–5 years, the overall survival rate was 139/245 (56.8%). In all, 16 children progressed to end-stage renal disease; thus, renal survival was 127/173 (91%). Those with primary renal/urologic conditions had lower renal survival than others (24/35 (68.6%) vs 134/139 (96.4%); P

Carbamazepine intoxication is common in the pediatric population. Highly protein-bound, carbamazepine is not removed efficiently through conventional hemodialysis. We describe the use of albumin-enhanced continuous venovenous hemodialysis (CVVHD) in a 10-year-old girl who developed coma and respiratory depression due to an intentional carbamazepine overdose (peak drug level of 44.8 μg/ml; therapeutic range: 8–12 μg/ml). Without intervention, the half-life of drug elimination is 25 to 60 hours in patients who are naive to carbamazepine and 12 to 20 hours in children on chronic carbamazepine therapy. In contrast, with albumin-enhanced CVVHD, we observed a half-life of 7 to 8 hours. The patient recovered rapidly and was discharged from hospital

Introduction: Adult patients with Sickle Cell Disease (SCD): 1) develop renal failure at an earlier age than non-SCD black patients with end stage renal disease and 2) renal transplant outcomes in patients with SCD are so inferior that many transplant programs will not consider patients with SCD as candidates. More research is needed to understand the development of renal disease in patients with SCD; particularly in the earlier stages in which interventions might be most successful. In non-SCD pediatric populations, 24 hour Ambulatory Blood Pressure Monitoring (ABPM) is the gold standard method to document hypertension as it has been shown to be a better surrogate outcome for end organ damage from hypertension. The association between hypertension (as defined by ABPM) and progressive kidney disease needs to be assessed in SCD. Objective: To identify baseline blood pressure (BP) abnormalities as measured by ABPM and conventional clinic measurement and to characterize factors associated with ABPM abnormalities among a cohort of sickle cell participants enrolled in a 5 year prospective study of hypertension and progressive kidney injury. Methods: Participants ages 5-21 yrs with HbSS or SB0 thalassemia were enrolled in a five year IRB approved prospective cohort study; participants 11-20 yrs were also eligible to undergo 24 hr ABPM. Demographics, therapies,and laboratory data (CBC, CMP, uric acid, LDH, cystatin c, and urine microalbumin/creatinine) were recorded. The pre-transfusion CBC was used for patients on chronic transfusion therapy. Clinic BP and 24 hr ABPM (using SpaceLabs 90217 monitors which records BP every 20 minutes while awake and 30 minutes while asleep for at least 24 hours) were measured. BP level norms were determined by pediatric BP tables created by the NHLBI (clinic BP) and American Heart Association (ABPM) for age and height. Abnormal nocturnal dipping is defined as 25% of blood pressure recordings exceeding the 95th percentile BP for normative data. Results: At the time of this abstract, 29/108 (27%) of participants were hypertensive at their baseline clinic visit and 24-hr ABPM has been conducted in 27 participants (7 were normotensive in clinic; 20 were normotensive during clinic visit). Twenty two of the 27 (81%) participants were identified with abnormal systolic nocturnal BP dipping and 15/27 (56%) had abnormal diastolic nocturnal BP dipping. Of concern, 10/27 (37%) participants had an increase in SBP while sleeping and 7/27 (26%) had an increase in DBP while sleeping. Among the seven participants with hypertension in clinic, all had abnormal nocturnal BP dipping. In those participants with normal clinic BP, 15/20 (75%) had abnormal systolic BP dipping. Nine (33%) participants had an abnormal nocturnal systolic BP load and 7 (26%) participants had abnormal nocturnal diastolic BP load. Eight of 10 participants with an increase in systolic BP while sleeping were on chronic transfusion therapy (p=0.06). Variables that may be associated with an increase in systolic BP while sleeping were: lower GFR (p=0.06), higher BMI (p=0.02), and higher hemoglobin (p=0.08). Participants on chronic transfusion had a higher mean nocturnal systolic BP load than participants on no chronic therapy or hydroxyurea therapy (p=0.04). Variables that may be associated with an abnormal nocturnal systolic BP load were: lower GFR (p Conclusion: Abnormal nocturnal BP is highly prevalent among SCD participants with and without hypertension in clinic. Blood therapy or need for blood therapy may be associated with abnormal nocturnal BP. Participants with abnormal nocturnal BP may have a lower GFR. Over time, this cohort will determine if abnormal nocturnal BP predicts a progressive decline in GFR in SCD as it does in non-SCD populations. Disclosures No relevant conflicts of interest to declare.

Background: Children hospitalized for cystic fibrosis related pulmonary exacerbation are at risk of acute kidney injury (AKI); yet the incidence of AKI using contemporary definitions has yet to be investigated. Methods: A retrospective chart review was performed for two era’s of about 2 years each. During the former era SCr was measured as per clinician. In the latter era, a standardized heightened surveillance program was implemented. Using the 2012 KDIGO AKI definition, we compared the incidence, severity of AKI, hospital costs and length of hospital stay between the two eras. Results: AKI was more common after surveillance implementation (23.8% vs. 15.2%; p < .001). The number of SCr measurements per each admission was increased in the surveillance era (. 3.4 ± 5.4 vs 2.1 ± 2.1; p < .001). Cost and length of stay were highest in those with AKI in the heightened surveillance era (p

Outcome in pediatric acute kidney injury (AKI) is in part related to diagnosis and intervention. Standard markers of severity of illness do not identify AKI. Modified RIFLE criteria are shown to identify patients who develop AKI, potentially allowing for early intervention.

To identify urine biomarkers predictive of acute kidney injury (AKI) in infants admitted to level 2 and 3 neonatal intensive care units with birth weight2000 g and 5-minute Apgar score ≤ 7.A nested case-control study was performed comparing 8 candidate urine AKI biomarkers in infants with AKI (defined as a rise in serum creatinine of at least 0.3 mg/dL or a serum creatinine elevation ≥ 1.7 mg/dL persisting for 3 days) and 24 infants from the described cohort without AKI. Urine was analyzed for neutrophil gelatinase-associated lipocalin, osteopontin, cystatin C, albumin, β(2) microglobulin, epithelial growth factor, uromodulin (UMOD), and kidney injury molecule 1.Compared with the infants without AKI, those with AKI had higher levels of urine cystatin C (1123 pg/mL [95% CI, 272-4635 pg/mL] vs 90 pg/mL [95% CI, 39-205 pg/mL]; P.004; area under the receiver operating characteristic curve [AUC] = 0.82), lower levels of UMOD (11.0 pg/mL [95% CI, 5.7-21.4 pg/mL] vs 26.2 pg/mL [95% CI, 17.4-39.4 pg/mL]; P.03; AUC = 0.77), and lower levels of epithelial growth factor (6.7 pg/mL [95% CI, 4.0-11.3 pg/mL] vs 17.4 pg/mL [95% CI, 12.7-23.8 pg/mL; P = .003; AUC = 0.82). Although the differences were not statistically significant, levels of urine neutrophil-associated gelatinase lipocalin, kidney injury molecule 1, and osteopontin trended higher in infants with AKI.Urinary biomarkers can predict AKI in neonates admitted to level 2 and 3 neonatal intensive care units.

Methotrexate, administered for treatment of pediatric and adult malignancies, is a direct renal toxin, which can lead to renal dysfunction, decreased methotrexate clearance, elevated methotrexate concentrations, and systemic toxicity. Although plasma methotrexate concentrations have been shown to decline precipitously after a single dose of glucarpidase, this drug is investigational and available only through compassionate use. Therefore, alternative treatments for methotrexate removal may be required. We describe a 13-year-old girl (body surface area 1.2 m(2)) with osteosarcoma who was treated with high-dose methotrexate 12 g/m(2) infused over 4 hours. Forty-eight hours after the infusion, her plasma methotrexate concentrations were elevated at 446 micromol/L. She exhibited severe signs of methotrexate toxicity, including encephalopathy, liver failure, and acute kidney injury, and could not tolerate conventional hemodialysis. Over the next 12 days, the patient was treated with continuous venovenous hemodialysis (CVVHD), single-pass albumin dialysis (SPAD), continuous venovenous hemodiafiltration (CVVHDF), and glucarpidase to enhance methotrexate elimination. Compared with standard CVVHD, SPAD did not significantly increase methotrexate removal as measured by elimination half-life and methotrexate saturation coefficient. The highest clearance rate among extracorporeal therapies was achieved by CVVHDF, with an effluent rate of 4950 ml/hour. The patient's clinical condition steadily improved, and all extracorporeal therapies were stopped 168 hours after methotrexate administration. The patient was discharged home and continued with chemotherapy, including methotrexate, which was dosed based on iothalamate glomerular filtration rates on the day before infusion. Although extracorporeal treatments appeared to enhance methotrexate clearance, the administration of glucarpidase resulted in the most rapid percentage decline (86%) in methotrexate concentration. Until glucarpidase is readily available, intermittent hemodialysis should be used to enhance methotrexate clearance. If the patient is unable to tolerate hemodialysis, use of CVVHDF with maximum effluent rates will enhance methotrexate clearance.

Outcomes in critically ill neonates have improved over the past three decades, yet high residual mortality and morbidity rates exist. Acute kidney injury (AKI) is not just an innocent by-stander in the critically ill patient. Research on incidence and outcomes of AKI in the critically ill neonatal population is scarce. The objective of this publication is to (a) review original articles on the short- and long-term outcomes after neonatal AKI, (b) highlight key articles on adults and children with AKI in order to demonstrate how such insights might be applied to neonates, and (c) suggest clinical research studies to fill the gaps in our understanding of neonatal AKI. To date, observational studies suggest high rates of AKI and poor outcomes in critically ill neonates. Neonates with AKI are at risk of developing chronic kidney disease and hypertension. Large prospective studies are needed to test definitions and to better understand risk factors, incidence, independent outcomes, and mechanisms that lead to poor short- and long-term outcomes. Early biomarkers of AKI need to be explored in critically ill neonates. Infants with AKI need to be followed for sequelae after AKI.