Reduced kidney function and hypertension in adolescents with low birth weight, NHANES 1999-2016.

BACKGROUND: Chronic kidney disease (CKD) is a major health problem, and the risk of CKD and hypertension in children born low birth weight (LBW) is under-recognized. We hypothesized that children born with LBW would have a higher prevalence of reduced kidney function and hypertension. METHODS: Using the National Health and Nutrition Examination Survey (NHANES), we conducted a cross-sectional study to evaluate whether LBW (< 2500 g), very low birth weight (VLBW < 1500 g), and large birth weight (BW) (> 4000 g) were associated with kidney disease using 4 different estimating equations. We used the Counahan-Barratt, updated Schwartz, CKiD-U25, and full age spectrum creatinine-based GFR estimating equations to evaluate associations between a history of LBW/VLBW/large BW and reduced kidney function (eGFR < 90 mL/min/1.73 m2) in children. We also assessed blood pressure (BP) using the old and new pediatric hypertension guidelines. RESULTS: Our analysis included 6336 children (age 12-15 years) in NHANES representing over 13 million US individuals. Using the updated Schwartz, the prevalence of reduced kidney function was 30.1% (25.2-35.6) for children born with LBW compared to 22.4% (20.5-24.3) in children with normal BW. Equations yielded different estimates of prevalence of reduced kidney function in LBW from 21.5% for Counahan-Barratt to 35.4% for CKiD-U25. Compared to those with normal BW, participants with LBW and VLBW had a 7.2 and 10.3% higher prevalence of elevated BP and a 2.4 and 14.6% higher prevalence of hypertension, respectively. CONCLUSIONS: Children born with LBW are at higher risk of reduced kidney function and hypertension than previously described. A higher resolution version of the Graphical abstract is available as Supplementary information.

Environmental lead exposure is associated with neurocognitive dysfunction in children with chronic kidney disease.

BACKGROUND: Environmental lead exposure is associated with cognitive impairment in healthy children, with deficits seen in intelligence quotient (IQ), attention, and behavior. Neurocognitive dysfunction is also a well-described complication among children with chronic kidney disease (CKD). The objective was to evaluate the association between blood lead levels (BLL) and performance on neurocognitive assessments in a cohort of children with CKD. METHODS: Cross-sectional study of children with mild to moderate CKD from the Chronic Kidney Disease in Children (CKiD) multicenter prospective cohort study. The primary exposure was BLL. The primary outcome was performance on age-specific neurocognitive assessments evaluating IQ, executive functioning, attention, hyperactivity, and behavior. Multivariable linear regression was used to evaluate the association between BLL and neurocognitive performance, adjusted for key sociodemographic and clinical variables. RESULTS: A total of 412 subjects were included with median age 15.4 years, median estimated GFR 39 mL/min/1.732, median BLL 1.2 mcg/dL, and median IQ score 99. In multivariable linear regression, higher BLL was associated with significantly lower IQ score (- 2.1 IQ points for every 1-mcg/dL increase in BLL, p = 0.029). Higher BLL was associated with worse scores on the Conners' Continuous Performance Test II Variability T-Score, a measure of inattention (+ 1.8 T-Score points for every 1-mcg/dL increase in BLL, p = 0.033). CONCLUSIONS: Low-level lead exposure is associated with significantly lower IQ and more inattention in children with CKD, a population already at high risk for neurocognitive dysfunction. Universal screening for elevated BLL should be considered for all children with CKD at age 12-24 months.

Vitamin D insufficiency, hemoglobin, and anemia in children with chronic kidney disease.

BACKGROUND: 25-Hydroxyvitamin D (25OHD) deficiency is common in children with chronic kidney disease (CKD). It has been associated with an increased risk for anemia in both healthy US children and in adults with CKD. This association has not been explored in children with CKD. METHODS: Children aged 1-16 enrolled in the Chronic Kidney Disease in Children (CKiD) study with mild to moderate kidney dysfunction, and with 25OHD measured at baseline (n = 580), were included in the analysis. The cross-sectional associations between 25OHD and hemoglobin (g/dL) and anemia were assessed. Anemia was defined as hemoglobin < 5th percentile for age and sex. RESULTS: Overall 334 (57.59%) children were vitamin D insufficient/deficient and 137 (23.62%) were anemic. Of those who were vitamin D insufficient/deficient, 95 (28.44%) were anemic. In the overall cohort, the odds of being anemic was 1.9 times higher (95% CI, 1.22-3.04, p < 0.01) in vitamin D insufficient/deficient vs sufficient children, when adjusting for covariates (age, sex, race [black, white, or other], body mass index (BMI), iohexol GFR (iGFR), erythropoietin stimulation agent (ESA) use, iron supplementation use, and underlying cause of CKD). Stratified by race, the odds of being anemic was 2.39 times higher (95% CI, 1.41-4.05, p = 0.001) in vitamin D insufficient/deficient vs vitamin D sufficient white children. The association between vitamin D status and anemia was not significant in black children. CONCLUSIONS: The data support our hypothesis that vitamin D insufficiency/deficiency increases the odds of anemia in children with CKD. The effect was strong and significant among white, but not black, children.

Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.

Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Pseudohypoaldosteronism type II (PHAII), a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis, has revealed previously unrecognized physiology orchestrating the balance between renal salt reabsorption and K(+) and H(+) excretion. Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families. KLHL3 mutations are either recessive or dominant, whereas CUL3 mutations are dominant and predominantly de novo. CUL3 and BTB-domain-containing kelch proteins such as KLHL3 are components of cullin-RING E3 ligase complexes that ubiquitinate substrates bound to kelch propeller domains. Dominant KLHL3 mutations are clustered in short segments within the kelch propeller and BTB domains implicated in substrate and cullin binding, respectively. Diverse CUL3 mutations all result in skipping of exon 9, producing an in-frame deletion. Because dominant KLHL3 and CUL3 mutations both phenocopy recessive loss-of-function KLHL3 mutations, they may abrogate ubiquitination of KLHL3 substrates. Disease features are reversed by thiazide diuretics, which inhibit the Na-Cl cotransporter in the distal nephron of the kidney; KLHL3 and CUL3 are expressed in this location, suggesting a mechanistic link between KLHL3 and CUL3 mutations, increased Na-Cl reabsorption, and disease pathogenesis. These findings demonstrate the utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis.

Renin-angiotensin II-aldosterone system blockers and time to renal replacement therapy in children with CKD.

BACKGROUND: Clinical care decisions to treat chronic kidney disease (CKD) in a growing child must often be made without the benefit of evidence from clinical trials. We used observational data from the Chronic Kidney Disease in Children cohort to estimate the effectiveness of renin-angiotensin II-aldosterone system blockade (RAAS) to delay renal replacement therapy (RRT) in children with CKD. METHODS: A total of 851 participants (median age: 11 years, median glomerular filtration rate [GFR]: 52 ml/min/1.73 m2, median urine protein to creatinine ratio: 0.35 mg/mg) were included. RAAS use was reported at annual study visits. Both Cox proportional hazards models with time-varying RAAS exposure and Cox marginal structural models (MSM) were used to evaluate the effect of RAAS use on time to RRT. Analyses were adjusted or weighted to control for age, male sex, glomerular diagnosis, GFR, nephrotic range proteinuria, anemia, elevated blood pressure, acidosis, elevated phosphate and elevated potassium. RESULTS: There were 217 RRT events over a 4.1-year median follow-up. At baseline, 472 children (55 %) were prevalent RAAS users, who were more likely to be older, have a glomerular etiology, have higher urine protein, be anemic, have elevated serum phosphate and potassium, take more medications, but less likely to have elevated blood pressure, compared with non-users. RAAS use was found to reduce the risk of RRT by 21 % (hazard ratio: 0.79) to 37 % (hazard ratio: 0.63) from standard regression adjustment and MSM models, respectively. CONCLUSIONS: These results support inferences from adult studies of a substantial benefit of RAAS use in pediatric CKD patients.

Toxic environmental exposures and kidney health in children.

High-level exposures to a number of agents are known to have direct nephrotoxic effects in children. A growing body of literature supports the hypothesis that chronic, relatively low-level exposure to various nephrotoxicants may also increase the risk for chronic kidney disease (CKD) or accelerate its progression. In this review we highlight several environmental nephrotoxicants and their association with CKD in children and adolescents. We also discuss unique epidemiological challenges in the use of kidney biomarkers in environmental nephrotoxicology.

Elevated uric acid and obesity-related cardiovascular disease risk factors among hypertensive youth.

BACKGROUND: Uric acid (UA) is associated with high blood pressure in adolescents and with left ventricular hypertrophy (LVH) and cardiovascular disease (CVD) in adults. We sought to determine if UA is independently associated with CVD risk factors and left ventricular mass (LVM) over time in hypertensive youth. METHODS: This was a 1-year prospective observational study of hypertensive children aged 3-19 years. Cross-sectional and longitudinal associations of serum UA with CVD risk factors and LVM were explored. RESULTS: Of the 49 children who completed both the baseline and 12-month assessments, at baseline the mean age was 13.8 years and mean UA was 5.5 mg/dL; 24% had elevated UA, 51% were overweight/obese and 39% had LVH. Measures of adiposity, low high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, LVM and LVH were all significantly associated with elevated UA at baseline, but not with change over time. Each 1 mg/dL increase in baseline UA was associated with a 2.5 g/m(2.7) increase in the LVM index at follow-up (95% confidence interval 0.64, 4.39; p = 0.01); after adjustment for age, sex, race, body mass index z-score, change in UA, time, blood pressure and medication use, this association was no longer significant. CONCLUSIONS: Hypertensive children with elevated UA have a higher prevalence of obesity-related CVD risk factors. Among hypertensive children, UA may be a marker of adiposity and not an independent CVD risk factor.

Vitamin D, race, and risk for anemia in children.

OBJECTIVE: To examine the association between 25-hydroxyvitamin D [25(OH)D] deficiency and anemia in a cohort of otherwise-healthy children and to determine whether race modifies the association between 25(OH)D status and hemoglobin (Hgb). STUDY DESIGN: Cross-sectional study of 10,410 children and adolescents ages 1-21 years from the 2001-2006 National Health and Nutrition Examination Survey. Anemia was defined as Hgb less than the 5th percentile for age and sex based on National Health and Nutrition Examination Survey III (1988-1994) data. RESULTS: Lower 25(OH)D levels were associated with increased risk for anemia; <30 ng/mL, adjusted OR 1.93, 95% CI 1.21-3.08, P = .006, and <20 ng/mL, OR 1.47, 95% CI 1.14-1.89, P = .004. In linear regression, small but significant increases in Hgb were noted in the upper quartiles of 25(OH)D compared with the lowest quartile (<20 ng/mL) in the full cohort. Results of race-stratified linear regression by 25(OH)D quartile in white children were similar to those observed in the full cohort, but in black children, an increase in Hgb in the upper 25(OH)D quartiles was only apparent compared with the lowest black race-specific quartile (<12 ng/mL). CONCLUSION: 25(OH)D deficiency is associated with increased risk of anemia in healthy US children, but the 25(OH)D threshold levels for lower Hgb are lower in black children in comparison with white children.

Factors associated with acute kidney injury in children receiving vancomycin.

BACKGROUND: As higher vancomycin doses have been used in children, concern for acute kidney injury (AKI) has increased. Data describing factors associated with AKI, particularly dose-related factors, are limited. OBJECTIVE: To determine the incidence of AKI in children receiving intravenous vancomycin and to identify factors associated with increased odds of AKI. METHODS: A retrospective review of patients admitted to a tertiary academic pediatric hospital from February 2009 to September 2010 was performed. Patients 3 months to <19 years old with normal kidney function, receiving vancomycin for at least 48 hours were included. Incidence of AKI was assessed as defined by the Pediatric-Modified RIFLE criteria. Patients with and without AKI were compared to determine factors associated with increased odds of AKI, focusing on vancomycin dose. RESULTS: Of 175 patients included, 24 (13.7%) met AKI criteria. In a multivariate regression, likelihood of AKI increased with each 5 mg/kg increase in vancomycin dose (odds ratio [OR] = 1.16; 95% CI = 1.01-1.33). Odds of AKI increased with each additional day of therapy (OR = 1.11; 95% CI = 1.01-1.22) and use of concomitant nephrotoxic medications (OR = 5.02; 95% CI = 1.09-23.19). The study was limited by small sample size and retrospective design. CONCLUSIONS: AKI was common in children receiving vancomycin. Higher doses of vancomycin were associated with increased odds of AKI. The risks and benefits of higher vancomycin dosing should be considered for each patient. Patients should be monitored closely for AKI, especially with higher doses, extended durations of therapy, or concomitant use of nephrotoxic medications.

Hemoglobin level and risk of hospitalization and mortality in children on peritoneal dialysis.

BACKGROUND: Clinical practice guidelines for management of anemia in children with end-stage kidney disease (ESKD) remain largely opinion-based. In this study, we evaluated the risk of mortality and hospitalization by hemoglobin (Hb) level in a large prevalent population of U.S. children on peritoneal dialysis (PD). METHODS: Hemoglobin levels in prevalent PD patients from the 2005 End Stage Renal Disease Clinical Performance Measures Project were linked with 5-year mortality and 4-year hospitalization records from the United States Renal Data System. RESULTS: Of the 468 patients included in the study, the mean age was 11 years, 55 % were male, 67 % were white, 254 (54 %) were hospitalized, and 23 (5 %) died. Median (interquartile range) Hb levels were 11.7 (10.7-12.6) g/dl, and 30 % had Hb levels of <11 g/dl. In adjusted survival analysis, Hb thresholds of 10, 11, or 12 g/dl were not associated with a significant difference in risk of death. The incidence rate ratio (IRR) of hospitalization for patients with a mean Hb of ≥11 g/dl was 0.56 (95 % CI 0.43-0.73). Compared to a reference range of Hb of 11 to <12, Hb of ≥12 g/dl was not associated with a significant difference in hospitalization risk (IRR 0.88; 95 % CI 0.61-1.25). Using age- and sex specific cut-offs for anemia, children who were not anemic had a 27 % decreased risk of hospitalization compared to those with anemia (IRR 0.73; 95 % CI 0.55-0.97). Compared to the first erythropoiesis stimulating agent (ESA) dosing quartile, higher ESA doses were associated with an increased risk of both hospitalization and mortality. CONCLUSIONS: U.S. children on PD with Hb levels of ≥11 g/dl were less likely to be hospitalized but had no observed difference in mortality. Children who were not anemic were also less likely to be hospitalized. Further study is necessary to elucidate whether a single optimal Hb level or a range applies to the pediatric ESKD population.

Impact of urine concentration adjustment method on associations between urine metals and estimated glomerular filtration rates (eGFR) in adolescents.

Positive associations between urine toxicant levels and measures of glomerular filtration rate (GFR) have been reported recently in a range of populations. The explanation for these associations, in a direction opposite that of traditional nephrotoxicity, is uncertain. Variation in associations by urine concentration adjustment approach has also been observed. Associations of urine cadmium, thallium and uranium in models of serum creatinine- and cystatin-C-based estimated GFR (eGFR) were examined using multiple linear regression in a cross-sectional study of adolescents residing near a lead smelter complex. Urine concentration adjustment approaches compared included urine creatinine, urine osmolality and no adjustment. Median age, blood lead and urine cadmium, thallium and uranium were 13.9 years, 4.0 µg/dL, 0.22, 0.27 and 0.04 g/g creatinine, respectively, in 512 adolescents. Urine cadmium and thallium were positively associated with serum creatinine-based eGFR only when urine creatinine was used to adjust for urine concentration (ß coefficient=3.1 mL/min/1.73 m(2); 95% confidence interval=1.4, 4.8 per each doubling of urine cadmium). Weaker positive associations, also only with urine creatinine adjustment, were observed between these metals and serum cystatin-C-based eGFR and between urine uranium and serum creatinine-based eGFR. Additional research using non-creatinine-based methods of adjustment for urine concentration is necessary.

Secondhand tobacco smoke: a source of lead exposure in US children and adolescents.

OBJECTIVES: We evaluated the relationship between secondhand tobacco smoke (SHS) exposure and blood lead levels in US children and adolescents. METHODS: We analyzed data from 6830 participants aged 3-19 years in the National Health and Nutrition Examination Survey (1999-2004) who were not active smokers and for whom SHS exposure information and blood lead measurements were available. RESULTS: After multivariable adjustment, participants in the highest quartile of serum cotinine (≥ 0.44 µg/L) had 28% (95% confidence interval = 21%, 36%) higher blood lead levels than had those in the lowest quartile (< 0.03 µg/L). Similarly, blood lead levels were 14% and 24% higher in children who lived with 1 or with 2 or more smokers, respectively, than they were in children living with no smokers. Among participants for whom lead dust information was available, the associations between SHS and blood lead levels were similar before and after adjustment for lead dust concentrations. CONCLUSIONS: SHS may contribute to increased blood lead levels in US children. Lead dust does not appear to mediate this association, suggesting inhalation as a major pathway of exposure. Eliminating SHS exposure could reduce lead exposure in children.

Association between common iron store markers and hemoglobin in children with chronic kidney disease.

BACKGROUND: Serum ferritin and transferrin saturation (TSAT) are used to assess iron status in children with chronic kidney disease (CKD), but their sensitivity in identifying those at risk of lower hemoglobin (HGB) values is unclear. METHODS: We assessed the association of iron status markers (ferritin, TSAT, and serum iron) with age- and gender-related HGB percentile in mild-to-moderate CKD in 304 children in the Chronic Kidney Disease in Children (CKiD) Study. Standardized HGB percentile values were examined by KDOQI-recommended ferritin (≥ 100 ng/ml) and TSAT (≥ 20 %) thresholds. Regression tree methods were used to identify iron status markers and clinical characteristics most associated with lower HGB percentiles. RESULTS: The cohort was 62 % male, 23 % African American, and 12 % Hispanic, median age 12 years, and median HGB 12.9 g/dl. 34 % had low TSAT and 93 % low ferritin as defined by KDOQI. Distribution of HGB percentile values was lower in those with ferritin ≥ 100 ng/ml, while TSAT ≥ 20 % was associated with only modest increase in HGB percentile. In regression tree analysis, lower glomerular filtration rate (GFR), serum iron <50 µg/dl and ferritin ≥ 100 ng/ml were most strongly associated with lower HGB percentile. CONCLUSIONS: The level of GFR was significantly associated with HGB. Higher serum ferritin was associated with lower HGB in this cohort. Low serum iron in the context of normal/increased ferritin and low HGB may be a useful indicator of iron-restricted erythropoiesis.

Setting an agenda for comparative effectiveness systematic reviews in CKD care.

Systematic reviews comparing the effectiveness of strategies to prevent, detect, and treat chronic kidney disease are needed to inform patient care. We engaged stakeholders in the chronic kidney disease community to prioritize topics for future comparative effectiveness research systematic reviews. We developed a preliminary list of suggested topics and stakeholders refined and ranked topics based on their importance. Among 46 topics identified, stakeholders nominated 18 as 'high' priority. Most pertained to strategies to slow disease progression, including: (a) treat proteinuria, (b) improve access to care, (c) treat hypertension, (d) use health information technology, and (e) implement dietary strategies. Most (15 of 18) topics had been previously studied with two or more randomized controlled trials, indicating feasibility of rigorous systematic reviews. Chronic kidney disease topics rated by stakeholders as 'high priority' are varied in scope and may lead to quality systematic reviews impacting practice and policy.

Pediatric Nurse and Pharmacist Knowledge of Acute Kidney Injury.

OBJECTIVES: In this study, we assessed the knowledge and experience of pediatric pharmacists and nurses at a US tertiary-care pediatric center regarding the risk factors for, recognition of, and best practices for managing an acute kidney injury (AKI) in children. METHODS: The authors developed a survey to assess the attitudes and knowledge of nurses and pharmacists regarding AKI in hospitalized children, which was reviewed by a small multidisciplinary group for content and length. The final 16-item survey consisted of demographic, self-assessment and attitude, and knowledge questions. All pediatric pharmacists and nurses at the study site received a voluntary online survey via e-mail. Data were analyzed by using descriptive statistics. RESULTS: A survey was sent to 620 nurses and 50 pharmacists; 148 (25%) and 22 (44%), respectively, completed it. Most respondents were <35 years old and had ≤10 years of experience in both their professions and pediatrics. A total of 72% of pediatric nurses felt identification of AKI was within their scope of practice, and ∼60% felt confident in their ability to do so. More than 80% of pediatric pharmacists felt confident in their abilities to adjust medication doses in pediatric patients with AKI, but <60% felt confident in their ability to estimate the glomerular filtration rate in these patients. Nurses and pharmacists were able to correctly identify specific AKI criteria 60% to 70% and 70% to 90% of the time, respectively. CONCLUSIONS: Although pediatric nurses and pharmacists have knowledge of AKI prevention and mitigation, gaps exist, and there is a desire for education in recognition of their key roles in the clinical team.

Prenatal blood lead levels and reduced preadolescent glomerular filtration rate: Modification by body mass index.

BACKGROUND: For the developing kidney, the prenatal period may represent a critical window of vulnerability to environmental insults resulting in permanent nephron loss. Given that the majority of nephron formation is complete in the 3rd trimester, we set out to test whether 1) prenatal lead exposure is associated with decreased preadolescent kidney function and 2) whether preadolescent obesity acts synergistically with early life lead exposure to reduce kidney function. METHODS: Our study included 453 mother-child pairs participating in the PROGRESS birth cohort. We assessed prenatal blood lead levels (BLLs) in samples collected in the 2nd and 3rd trimesters and at delivery, as well as tibial and patellar bone lead measures assessed one-month postpartum. Preadolescent estimated glomerular filtration rate (eGFR) was derived from serum levels of creatinine and/or cystatin C measured at age 8-12 years. We applied linear regression to assess the relationship between prenatal bone and BLL with preadolescent eGFR, and adjusted for covariates including age, sex, BMI z-score, indoor tobacco smoke exposure, and socioeconomic status. We also examined sex-specific associations and tested for effect modification by BMI status. RESULTS: We observed null associations between prenatal lead exposure and eGFR. However, in interaction analyses we found that among overweight children, there was an inverse association between BLL (assessed at 2nd and 3rd trimester and at delivery) and preadolescent eGFR. For example, among overweight participants, a one ln-unit increase in 2nd trimester BLL was associated with a 10.5 unit decrease in cystatin C-based eGFR (95% CI: -18.1, -2.8; p = 0.008). Regardless of lead exposure, we also observed null relationships between BMI z-score and eGFR overall, as well as among overweight participants. However, among participants with preadolescent obesity, we observed a significant 5.9-unit decrease in eGFR. We observed no evidence of sex-specific effects. CONCLUSIONS: Our findings, if confirmed in other studies, suggest a complex interplay between the combined adverse effects of adiposity and perinatal lead exposure as they relate to adolescent kidney function. Future studies will assess kidney function and adiposity trajectories through adolescence to better understand environmental risk factors for kidney function decline.

Secondary hyperparathyroidism and anemia in children treated by hemodialysis.

BACKGROUND: Many patients treated using hemodialysis remain anemic despite exogenous erythropoietin therapy, suggesting that the anemia experienced by these patients is multifactorial in cause. Iron deficiency, infection, inflammation, and malnutrition have been implicated in this process. Additionally, secondary hyperparathyroidism has been associated with anemia in adults, but few data exist about this topic in children. STUDY DESIGN: Cross-sectional retrospective. SETTING & PARTICIPANTS: Children treated in hemodialysis centers (N = 588) within the Centers for Medicare & Medicaid Services' 2002 Clinical Performance Measures Project. PREDICTOR: Intact parathyroid hormone (iPTH) levels assessed in October, November, and December 2001 and categorized as quintiles. OUTCOMES & MEASUREMENTS: Achievement of serum hemoglobin level > or = 11 g/dL was assessed using Poisson regression adjusting for sex, age, race, dialysis vintage, vascular access type, single-pool Kt/V, serum albumin level, normalized protein catabolic rate, calcium-phosphorus product, and erythropoietin alfa dose. RESULTS: Using the second quintile (iPTH, 103-224 pg/mL) as the reference quintile, there was no association between iPTH quintile and achievement of the hemoglobin goal: quintile 1 prevalence ratio, 1.0 (95% CI, 0.9-1.2); quintile 3, 0.95 (95% CI, 0.8-1.1); quintile 4, 0.99 (95% CI, 0.8-1.2); and quintile 5, 0.97 (95% CI, 0.8-1.1). Only serum albumin level >/= 3.5 g/dL (bromocresol green assay method) or > or = 3.2 g/dL (bromocresol purple assay method) was significantly associated with meeting the hemoglobin goal: 1.4 (95% CI, 1.2-1.6). LIMITATIONS: The simultaneous collection of iPTH and hemoglobin limits causal inference. Iron stores and iron therapy are potential confounders not accounted for in this study. CONCLUSIONS: In the largest study of this topic in children, no association was found between iPTH level and achievement of a hemoglobin level > or = 11 g/dL. Serum albumin level was associated strongly with achievement of the hemoglobin goal.

Acute Kidney Injury in Hospitalized Pediatric Patients: A Review of Research.

INTRODUCTION: Pediatric patients who develop acute kidney injury (AKI) while hospitalized have longer hospital stays, increased morbidity and mortality, and are at an increased risk for developing chronic kidney disease. Early recognition of AKI is becoming a major clinical focus. There is little research focusing on nursing interventions that may affect a pediatric patient's risk for developing AKI. The purpose of this review is to summarize reported predictors of AKI to improve its early recognition and treatment among hospitalized pediatric patients. METHODS: A review of research was conducted to further identify risk factors of AKI among noncritically ill hospitalized pediatric patients. RESULTS: The current literature demonstrated inconsistent findings in early recognition of AKI among hospitalized pediatric patients. DISCUSSION: Interventions for early recognition and treatment of AKI should consider other variables, such as previous history of AKI and fluid status as risk factors, warranting additional research.

Serum-Associated Antibiotic Tolerance in Pediatric Clinical Isolates of Pseudomonas aeruginosa.

BACKGROUND: When grown in human serum, laboratory isolates of Pseudomonas aeruginosa exhibit tolerance to antibiotics at inhibitory concentrations. This phenomenon, known as serum-associated antibiotic tolerance (SAT), could lead to clinical treatment failure of pseudomonal infections. Our purpose in this study was to determine the prevalence and clinical impact of SAT in Pseudomonas isolates in hospitalized children. METHODS: The SAT phenotype was assessed in patients aged <18 years admitted with respiratory or blood cultures positive for P. aeruginosa. The SAT phenotype was a priori defined as a ≥2-log increase in colony-forming units when grown in human serum compared with Luria-Bertani medium in the presence of minocycline or tobramycin. RESULTS: SAT was detected in 29 (64%) patients. Fourteen patients each (34%) had cystic fibrosis (CF) and tracheostomies. Patient demographics and comorbidities did not differ by SAT status. Among CF patients, SAT was associated with longer duration of intravenous antibiotics (10 days vs 5 days; P < .01). CONCLUSIONS: This study establishes that SAT exists in P. aeruginosa from human serum and may be a novel factor that contributes to differences in clinical outcomes. Future research should investigate the mechanisms that contribute to SAT in order to identify novel targets for adjunctive antimicrobial therapies.