Defining pediatric community-acquired acute kidney injury: an observational study.

BACKGROUND: Pediatric acute kidney injury (AKI) is associated with long-term morbidity and mortality; however, outcomes improve when AKI is detected earlier. Current definitions of AKI use baseline creatinine; community-acquired AKI (CA-AKI) is difficult to define and detect in the pediatric emergency department (ED) when no baseline creatinine is available. Our objective was to compare age- and gender-based creatinine norms to the traditional baseline (lowest creatinine in previous 3 months) to diagnose CA-AKI. METHODS: This was a retrospective cross-sectional study conducted in children 1 month-18 years of age seen in the pediatric ED in whom a creatinine was obtained. RESULTS: Per the Kidney Disease Improving Global Outcomes AKI definition in encounters with baseline creatinine available, 343/2338 (14.7%) had CA-AKI. When the upper limit of the age- and gender-based creatinine norm was applied as a surrogate baseline creatinine, CA-AKI was diagnosed in 1.5% of encounters (239/15,486). Additionally, CA-AKI was diagnosed in 178 cases using the upper limit of age- and gender-based creatinine norms only, as these cases did not have a baseline creatinine. CONCLUSIONS: Age- and gender-based creatinine norms can be applied as a surrogate baseline to detect CA-AKI in all children regardless of whether baseline creatinine is available, potentially detecting it earlier.

Community-acquired Acute Kidney Injury Among Children Seen in the Pediatric Emergency Department.

OBJECTIVES: Acute kidney injury (AKI) is a significant risk factor for morbidity and mortality in children. Little is known about community-acquired AKI (CA-AKI) in the pediatric emergency department (PED). Early recognition of AKI allows for nephroprotective measures. The goal of this investigation was to determine the incidence of CA-AKI and the frequency of clinician identified CA-AKI to better inform future nephroprotective interventions. METHODS: This was a retrospective cross-sectional study in the PED of a children's hospital. Children 1 month to 18 years of age seen in the PED from January 1 to December 31, 2015, and in whom at least one creatinine level was obtained were included. Patients with chronic kidney disease or end-stage renal disease or who died in the PED were excluded. Patients had CA-AKI based on modified Kidney Disease-Improving Global Outcomes criteria using the creatinine obtained in the PED compared to age-specific norms. Patients were considered identified if the PED clinician diagnosed AKI. The primary outcome was the incidence of CA-AKI. Secondary outcomes included frequency of AKI identification, nephrotoxic medication use, hospital length of stay, renal replacement therapy, and death. Fisher exact test or Pearson's chi-square test was used to calculate odds ratio (OR) with 95% confidence intervals (CIs); multivariable analyses were performed using logistic regression. RESULTS: In 2015 there were 119,151 PED visits; 15,486 met inclusion criteria. CA-AKI was present in 239 of 15,486 (1.5%) encounters. AKI was identified by PED clinicians in 46 of 239 (19%) of encounters and by the inpatient team in 123 of 199 (62%) of the encounters admitted. AKI was never recognized by a PED or inpatient clinician in 74 of 199 (37%) encounters. Encounters with AKI correctly diagnosed were older (13 years old vs. 10 years old, p = 0.0114), had more severe (stage 2 or 3) AKI (OR = 5.5, 95% CI = 2.6-11.8), and were more likely to be admitted (OR = 10.3, 95% CI = 1.38-77.4) than encounters with missed AKI. CONCLUSIONS: CA-AKI remains an underrecognized entity in the PED. Better tools for early recognition of AKI in the busy PED environment are needed.

A Library of Rare α1-Antitrypsin (AAT) Variant Phenotypes to Aid in the Diagnosis of AAT Deficiency.

OBJECTIVES: α1-Antitrypsin (AAT) deficiency is a hereditary disorder due to defective production of the serine protease inhibitor, AAT, which can cause lung and liver diseases. Severity of disease depends particularly on the phenotypic representation of AAT variants in the patient. METHODS: In this study, we present determination of seven common and nine rare variant phenotypes of AAT using pediatric samples collected in Texas Children's Hospital to address the knowledge gap in the identification of rare variants. We tested 16 different AAT variants that had been stored in a -80 °C freezer over the years to add to the reference library of AAT variants. The gold-standard isoelectric focusing electrophoresis method was used for analysis and interpretation of AAT variants. Each variant was inspected visually by comparing multiple bands, unique to phenotypic identity, with a previously identified pattern. RESULTS: Seven common M, S, and Z variants were identified as M1M1, M2M2, M1M2, MS, SS, SZ, and ZZ. Nine rare variants were identified as FM, FS, FZ, PM, XM, YM, IM, TS, and EP. These were interpreted independently and in a blinded manner by an experienced technologist and two clinical chemists from two different institutions. CONCLUSIONS: Our results add to the reference library to identify the rare variant phenotypes of AAT protein. This report will guide clinical laboratories for proper assessment of rare variants and in turn contribute to accurate diagnosis and management of AAT deficiency.

Effect of interference from hemolysis, icterus and lipemia on routine pediatric clinical chemistry assays.

BACKGROUND: Clinical laboratory assays can be affected by interferents like hemoglobin (Hb), lipids and bilirubin. We evaluated the effect of these interferences on pediatric samples for different chemistry assays. Further we established cut-off indices above which these interferences confound sample results. METHODS: Three separate serum pools were spiked with increasing concentrations of hemolysate or intralipid or bilirubin and different analytes were analyzed. The Hemolysis-(H), Lipemia-(T) and Icterus-(I) indices were measured on Vitros 5600. Analytes affected by lipemia were treated with LipoClear ® and re-analyzed. All the measured analytes were compromised by gross hemolysis (H-Index >1000). RESULTS: Except lipase and magnesium (Mg(++)), all other analytes were affected by moderate (H-Index >250) and significant hemolysis (H-Index >500). Low estradiol levels showed a significant effect at severe icterus (I-Index >20.0). C3, C4, Ceruloplasmin, Haptoglobin, Immunoglobulins (Ig) and Vitamin D were significantly affected by moderate (T-Index >100) and severe (T-Index >500) lipemia. LipoClear ® treatment significantly attenuated the lipemic interference on the above analytes except for C3, C4, and IgG. CONCLUSIONS: Accurate reporting of pediatric samples for the analytes affected by common interferences will lead to better clinical interpretation.

Performance characteristics of urinalyses for the diagnosis of pediatric urinary tract infection.

PURPOSE: The purpose of this study is to determine whether point-of-care (POCT) urinalysis (UA) is as accurate as laboratory-performed UA in diagnosing urinary tract infections (UTIs) in the pediatric emergency department (PED). BASIC PROCEDURES: This was a retrospective series of children (0-18 years old) seen at a tertiary care PED from July 2008 to December 2012 in whom UA and urine culture were obtained. Urinalyses were considered positive if leukocyte esterase and/or nitrites were positive. Performance characteristics for the 2 types of UAs were calculated using urine culture as the reference standard. MAIN FINDINGS: A total of 43452 specimens were sent for laboratory-performed UA and culture, and 6492, for POCT UA and culture (in 2908 specimens, both UAs were performed). Sixty-four percent of specimens were from girls, 51% were catheterized, and 7.5% had UTIs. The sensitivity of POCT UAs and laboratory-performed UAs was 82.5% (confidence interval [CI], 79.4%-85.3%) and 89.1% (CI, 86.4%-88.8%), respectively. The superior performance of laboratory-performed UAs was driven by the sensitivity of microscopy. Laboratory-performed UAs were more sensitive than the POCT in girls (90.6% [CI, 89.4%-91.8%] vs 82.8% [79.4%-85.8%]). PRINCIPAL CONCLUSIONS: Although POCT UAs offer more rapid turnaround times, the sensitivity is greater for laboratory-performed UAs. Given the difficulty in following up PED patients after discharge as well as the potential morbidity from untreated UTIs, the rapidity of the POCT UA must be balanced against the lower sensitivity of this assay. The benefit of more accurate diagnosis may outweigh the potentially longer PED length of stay associated with a laboratory-performed UA.

Performance of a rapid influenza test in children during the H1N1 2009 influenza a outbreak.

OBJECTIVE: To evaluate the performance of a rapid influenza diagnostic test (RIDT) in detecting H1N1 2009 influenza A virus in respiratory samples from pediatric patients in comparison to that of real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) and viral culture. Methodology. This was a cross-sectional diagnostic-accuracy study conducted at a tertiary care children's hospital. Patients for whom the RIDT (BinaxNOW [Binax, Inc, Portland, ME]), viral culture, and rRT-PCR results were known were included. Sensitivity, specificity, and likelihood ratios (LRs) were calculated. RESULTS: A total of 3030 specimens had RIDT results paired with both rRT-PCR and viral culture results. With rRT-PCR as the reference, overall test sensitivity was 45% (95% confidence interval [CI]: 43.3%-46.3%) and specificity was 98.6% (95% CI: 98.1%-99%). Positive and negative LRs were 32.9 (95% CI: 22.9-45.4) and 0.56 (95% CI: 0.54-0.58), respectively. RIDT sensitivity was significantly higher in young infants and children younger than 2 years than in older children. Using viral culture as the reference standard, RIDT sensitivity was 55.5% (95% CI: 51.9%-95.6%) and specificity was 95.6% (95% CI: 95%-96.1%). The positive and negative LRs were 12.6 and 0.47, respectively. CONCLUSIONS: The RIDT had relatively poor sensitivity but excellent specificity in this consecutive series of respiratory specimens obtained from pediatric patients. Although a positive RIDT result was highly accurate in predicting infection with influenza type A H1N1 2009 in children, a negative RIDT result did not preclude a child having H1N1. Therefore, for children at high risk with influenza-like illnesses during high-prevalence periods of influenza, empiric initiation of antiviral therapy should be considered for patients with a negative RIDT result.

Standardization of Light Scattering Measurement in Conjunction With Immunochemical Analysis.

Light scattering methods for the physical analysis of synthetic and biological polymers necessitates the use of scattering standards and absolute light scattering measurements. Standardization has not been employed when light scattering has been used to monitor immunochemical reactions using a kinetic or thermodynamic mode. The concentration of a specific protein present in a complex matrix such as urine, serum or cerebrospinal fluid, is measured by reacting the protein of interest with its specific antibody and then measuring the excess light scattering of the solution produced by the formation of antigen antibody complexes. The lack of established light scattering standards in the area of immunochemical measurements makes instrumental quality control difficult and has hindered direct comparison of data among investigators. Both solid and liquid light scattering standards would be necessary to encompass the wide range of instrumentation currently in use. Several solid standards which have been used in the past include reflecting diffusers such as vitrolite, magnesium carbonate crystals with a ground surface, magnesium oxide coatings on magnesium carbonate crystal, casein paint on vitrolite, and solid opal glass transmitting diffusers such as flashed opal glass and solid opal glass. These standards, while applicable to manual light scattering photometers, are not suitable for recently developed automated instrumentation. Liquid standards in the form of Ludox®, solutions of polystyrene, suspensions of small diameter latex spheres and even pure organic solvents could be used more easily with the continuous flow and discrete automated analyzers. The introduction of instrumental standards at this level of analysis would result in improved overall quality control and facilitate data and method comparison between laboratories.