Pediatric continuous renal replacement therapy: have practice changes changed outcomes? A large single-center ten-year retrospective evaluation.

BACKGROUND: To evaluate changes in population characteristics and outcomes in a large single-center pediatric patient cohort treated with continuous renal replacement therapy (CRRT) over a 10 year course, coincident with multiple institutional practice changes in CRRT delivery. METHODS: A retrospective cohort study with comparative analysis of all patients treated from 2004 to 2013 with CRRT in the neonatal, pediatric, and cardiovascular intensive care units within a free-standing pediatric tertiary care hospital. RESULTS: Three hundred eleven total patients were identified, 38 of whom received concurrent treatment with extracorporeal membrane oxygenation. 273 patients received CRRT only and were compared in two study eras (2004-2008 n = 129; 2009-2013 n = 144). Across eras, mean patient age decreased (9.2 vs 7.7 years, p = 0.08), and the most common principal diagnosis changed from cardiac to liver disease. There was an increase in patients treated with continuous renal replacement therapy between cohorts for acute kidney injury of multi factorial etiology (44% vs 56%) and a decrease in treated patients with sepsis (21% vs 11%, p = 0.04). There was no significant difference in survival to hospital discharge between eras (47% vs 49%). Improvement in outpatient follow-up after discharge amongst survivors was seen between study eras (33% vs 54%). CONCLUSIONS: Despite multiple institutional practice changes in provision of CRRT, few changes were seen regarding patient demographics, diseases treated, indications for therapy, and survival over 10 years at a single tertiary care. Recognition of need for follow-up nephrology care following CRRT is improving. Ongoing assessment of the patient population in a changing landscape of care for critically ill pediatric patients remains important.

Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene.

PURPOSE: To investigate the utility of whole-exome sequencing (WES) to define a molecular diagnosis for patients clinically diagnosed with congenital anomalies of kidney and urinary tract (CAKUT). METHODS: WES was performed in 62 families with CAKUT. WES data were analyzed for single-nucleotide variants (SNVs) in 35 known CAKUT genes, putatively deleterious sequence changes in new candidate genes, and potentially disease-associated copy-number variants (CNVs). RESULTS: In approximately 5% of families, pathogenic SNVs were identified in PAX2, HNF1B, and EYA1. Observed phenotypes in these families expand the current understanding about the role of these genes in CAKUT. Four pathogenic CNVs were also identified using two CNV detection tools. In addition, we found one deleterious de novo SNV in FOXP1 among the 62 families with CAKUT. The clinical database of the Baylor Miraca Genetics laboratory was queried and seven additional unrelated individuals with novel de novo SNVs in FOXP1 were identified. Six of these eight individuals with FOXP1 SNVs have syndromic urinary tract defects, implicating this gene in urinary tract development. CONCLUSION: We conclude that WES can be used to identify molecular etiology (SNVs, CNVs) in a subset of individuals with CAKUT. WES can also help identify novel CAKUT genes.Genet Med 19 4, 412-420.

Clinical Characteristics and Outcomes of Drug-Induced Acute Kidney Injury Cases.

Introduction: Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI. Methods: We analyzed data from the Drug-Induced Renal Injury Consortium (DIRECT) study (NCT02159209), an international, multicenter, observational cohort study of enriched clinically adjudicated DI-AKI cases. Cases met the primary inclusion criteria if the patient was exposed to at least 1 nephrotoxic drug for a minimum of 24 hours prior to AKI onset. Cases were clinically adjudicated, and inter-rater reliability (IRR) was measured using Krippendorff's alpha. Variables associated with DI-AKI were identified using L1 regularized multivariable logistic regression. Model performance was assessed using the area under the receiver operating characteristic curve (ROC AUC). Results: A total of 314 AKI cases met the eligibility criteria for this analysis, and 271 (86%) cases were adjudicated as DI-AKI. The majority of the AKI cases were recruited from the United States (68%). The most frequent causal nephrotoxic drugs were vancomycin (48.7%), nonsteroidal antiinflammatory drugs (18.2%), and piperacillin/tazobactam (17.8%). The IRR for DI-AKI adjudication was 0.309. The multivariable model identified age, vascular capacity, hyperglycemia, infections, pyuria, serum creatinine (SCr) trends, and contrast media as significant predictors of DI-AKI with good performance (ROC AUC 0.86). Conclusion: The identification of DI-AKI is challenging even with comprehensive adjudication by experienced nephrologists. Our analysis identified key clinical characteristics and outcomes of DI-AKI compared to other AKI etiologies.

The Coding Impact of Acute Kidney Injury in Pediatric Hospital Documentation.

Background: Acute kidney injury (AKI) increases patient morbidity and mortality. In value-based care, the documented and coded diagnoses during hospitalization influences an encounter's relative weight (RW), including severity of illness (SOI), and risk of mortality, which ultimately determines reimbursement for care. The impact of a secondary diagnosis of AKI on RW in pediatric patients has not been evaluated. Methods: A single-center, retrospective observational study was conducted over six months. The institutional coding database was queried for secondary diagnoses signifying AKI. The RW for each case was determined with and without an AKI secondary diagnosis. Patients were further stratified by their SOI score to evaluate change in RW and SOI. Results: Over a six-month period, 372 patients had a secondary AKI diagnosis, with a mean RW 2.14 decreasing to a mean RW 1.83 without an AKI diagnosis (p = 2.2e-16). When stratified by SOI, one patient had SOI 1 with RW change -0.286; six patients had SOI 2 with mean RW change -0.0669; 189 patients had SOI 3 with mean RW change -1.862 (p=2.23E-16); and 176 patients had SOI 4 with mean RW change -0.452 (p=9.46E-14), when the AKI secondary diagnosis was removed. Conclusions: Significant negative changes in RW were observed when AKI was removed, suggesting diagnostic omission may result in inaccurately lesser representation of patient medical complexity and severity of illness upon hospitalization coding, which may lower reimbursement.

Regional citrate anticoagulation for continuous renal replacement therapy in pediatric patients with liver failure.

Pediatric liver failure patients frequently develop multiple organ failure and require continuous renal replacement therapy (CRRT) as part of supportive therapy in the pediatric intensive care unit. While many centers employ no anticoagulation for fear of bleeding complications, balanced coagulation disturbance predisposes these patients to clotting as well as bleeding, making maintenance of longer circuit life to deliver adequate dialysis clearance challenging. Regional citrate anticoagulation (RCA) is an attractive option as it avoids systemic anticoagulation, but since citrate metabolism is impaired in liver failure, concerns about toxicity has limited its use. Pediatric data on RCA with liver failure is very scarce. We aimed to establish safety and efficacy of RCA in pediatric liver failure patients on CRRT. Retrospective review of pediatric patients with liver failure receiving CRRT over 30 months. Demographic data and CRRT related data were collected by chart review. Citrate accumulation (CA) was defined as total calcium (mg/dl) /ionized calcium (mmol/L) ratio >2.5 for > 48 hours. Efficacy was assessed by filter life. Safety was assessed by frequency of adverse events ((AEs) defined as bleeding, hemodynamic instability, arrhythmias). Fifty-one patients (median age 3.5 (IQR 0.75-14.2) years) received 861 CRRT days; 70% experienced at least one episode of CA, only 37% were recorded as such in the medical record. AE rate was 93/1000 CRRT days and did not differ between CA days and others. Median filter life was 66 hours (IQR 29-74); 63% filters lasted longer than 48 hrs. Though common, CA was not associated with increased AEs on in pediatric liver failure patients on CRRT receiving RCA. Filter life was adequate. RCA appears an effective anticoagulation for CRRT in pediatric liver failure. Application of a structured definition would increase recognition of CA to allow timely intervention.

In vivo heat inactivation of serum can distinguish false positive cross matches in renal transplants.

INTRODUCTION: Renal transplants have traditionally been performed despite positive cross match if results are presumptively due to IgM antibodies. False positives have been distinguishable from true positives by dithiothreitol or dithioerythritol treatment to inactivate IgM antibodies. Heat inactivation, which renders the antibodies inactive, is an alternative to chemical amelioration. METHODS: We retrospectively evaluated clinical outcomes of patients who had positive cross matches presumed to be falsely positive as determined by treatment with heat inactivation compared to controls with negative cross matches over a six-year period. A total of 414 transplanted patients had available cross match data: 355 with a negative cross match and 59 with a positive cross match rendered negative after heat inactivation. Serum creatinine was reviewed at 6, 12 and 24 months posttransplant. RESULTS: Graft function was considered stable at 12 and 24 months post-transplant if the change in creatinine compared to the 6-month value was >0.5 mg/dL. Repeated and nonrepeated measures analysis showed equivalence in the change in sCr from 6 to 12 (p = 0.525) and from 6 to 24 months (p = 0.752). Kaplan-Meier curves to evaluate graft survival demonstrated no significant difference in function over 24 months. Curves were censored for patient death, treated as death with functioning (p = 0.48) and nonfunctioning (p = 0.64) grafts. DISCUSSIONS: We have demonstrated comparable long-term function and survival for living donor renal transplants using heat inactivation to detect false positive cross matches. This simple and cost-effective method can be used to safely evaluate histocompatibility for living donor renal transplant recipients.

Biotechnology apprenticeship for secondary-level students: teaching advanced cell culture techniques for research.

The purpose of this article is to discuss small-group apprenticeships (SGAs) as a method to instruct cell culture techniques to high school participants. The study aimed to teach cell culture practices and to introduce advanced imaging techniques to solve various biomedical engineering problems. Participants designed and completed experiments using both flow cytometry and laser scanning cytometry during the 1-month summer apprenticeship. In addition to effectively and efficiently teaching cell biology laboratory techniques, this course design provided an opportunity for research training, career exploration, and mentoring. Students participated in active research projects, working with a skilled interdisciplinary team of researchers in a large research institution with access to state-of-the-art instrumentation. The instructors, composed of graduate students, laboratory managers, and principal investigators, worked well together to present a real and worthwhile research experience. The students enjoyed learning cell culture techniques while contributing to active research projects. The institution's researchers were equally enthusiastic to instruct and serve as mentors. In this article, we clarify and illuminate the value of small-group laboratory apprenticeships to the institution and the students by presenting the results and experiences of seven middle and high school participants and their instructors.

Peritoneal dialysis does not adversely affect kidney function recovery after congenital heart surgery.

PURPOSE: Acute kidney injury (AKI) after cardiopulmonary bypass surgery to correct congenital heart disease is common. We prevent fluid overload and further cardiac compromise in oliguric infants with continuous peritoneal dialysis (CPD). The effect of CPD on kidney recovery is unknown, thus indications to discontinue CPD are unclear. We aimed to determine if CPD affects kidney recovery, measured by urine output and novel urinary AKI biomarker concentrations. METHODS: Twenty infants <90 days old with congenital heart disease who underwent bypass surgery and were post-operatively treated with CPD were randomized at the time of clinical readiness for CPD discontinuation to 1) discontinue CPD (control) or 2) continue 24 h more CPD (experimental). Urine output (ml/kg per h), total output (ml/kg per h) and urinary neutrophil gelatinase-associated lipocalin, interleukin-18, liver-type fatty acid binding protein, and kidney injury molecule-1 were assessed post-surgery until CPD catheter removal. RESULTS: 24 hours preceding randomization, there were no differences in mean urine output or total output; 24 hours post-randomization, the control group had higher mean urine output (4.2 ± 2.6 ml/kg per h vs. 2.8 ± 2.0 ml/kg per h, p = 0.02) but lower total output (6.3 ± 2.1 ml/kg per h vs. 4.7 ± 2.7 ml/kg per h, p = 0.01). Median biomarker concentrations did not differ significantly between groups at any time point. CONCLUSIONS: Our results suggest renal replacement therapy does not change the time course of kidney function recovery.

Circulating blood volumes: a review of measurement techniques and a meta-analysis in children.

The accurate determination of circulating blood volume (CBV) in children has many clinical applications. The purposes of this article were to review currently available CBV measurement techniques and perform a meta-analysis using values from many small-scale studies that calculated CBV values for normal healthy children. A literature review demonstrated numerous methods by which to determine CBV. However, these methods necessitate repetitive blood sampling, require the introduction of foreign substances into the bloodstream, or address the uncertainty of substance distribution and clearance. Many small-scale studies have calculated CBV values for normal healthy children, and we performed a meta-analysis using these values. Age groups were defined, and within each group, means +/- 1 and 2 standard deviations were compared. A pooled estimate of mean blood volume and a 95% confidence interval was calculated after Q-statistics calculations indicated that the groups were homogeneous. Mean values showed agreement with typically accepted normal values. A large-scale study should be repeated when a gold standard for CBV measurements is developed.