Nephrotoxic Medication Exposure Research Articles

Acute Kidney Injury in Relation to Nephrotoxic Medication Use Among Critically Ill Children in the Paediatric Intensive Care Unit.

Background: Critically ill children are vulnerable to acute kidney injury (AKI) and are often exposed to nephrotoxic medications. Objectives: We aimed to investigate the association between nephrotoxic medications and the risk of AKI in critically ill children admitted to our paediatric intensive care unit (PICU). Methods: Patients aged > 1 month to ≤18 years old were prospectively recruited from 6/2020 to 6/2021. The medication records from 14 days prior to PICU admission to PICU discharge were reviewed. Medication-exposure intensity was defined as the number of concomitant nephrotoxic medications. The relative risk (RR) of nephrotoxic medication exposure indices and other potential predictors for AKI development were determined. Results: Altogether 253 episodes of admissions (median [IQR] age of 4.9 [9.6] years) were enrolled. The AKI incidence was 41.9% and 69.2% of the patients were exposed to ≥1 of the 47 nephrotoxic medications. The total nephrotoxic medication dose (RR: 1.01 [1.00, 1.02]) and medication-exposure intensity (RR: 1.381 [1.101, 1.732]) were significantly associated with AKI development. The risk of AKI increased when the medication-exposure intensity was ≥4 (RR: 3.687 (1.320, 10.301)). During their PICU stay, children with AKI received a higher number (P < .01), total dose (P < .01) and medication exposure intensity (P < .01) of nephrotoxic medications. Children with AKI who received nephrotoxic medications were more likely to have a persistently higher peak-to-baseline ratio (P = .046). Conclusion: Nephrotoxic medication exposure significantly increased the risk of AKI development among critically ill children. The use of nephrotoxic medications among critically ill children at risk for AKI should be monitored frequently.

Pattern and prognostic factors for kidney function progression in survivors of children with acute kidney injury: a cohort study

ObjectiveTo examine the pattern of kidney function progression after acute kidney injury (AKI) and identify the associated risk factors.DesignA prospective cohort study was conducted from June 2020 to June 2021...

The Utility of Urinary NGAL as an Alternative for Serum Creatinine to Detect Acute Kidney Injury in Infants Exposed to Nephrotoxic Medications in the Neonatal Intensive Care Unit

Introduction: Nephrotoxic medication (NTM) exposure is commonly associated with acute kidney injury (AKI) in the neonatal intensive care unit (NICU). Baby Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) is a quality improvement program that assesses for AKI in those exposed to NTM with daily serum creatinine (SCr) levels. However, blood draws for SCr are invasive and have clinical disadvantages. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a promising indicator of AKI. We tested the hypothesis that uNGAL could reliably screen for NTM-AKI in the Baby NINJA program. Methods: This two-center prospective study screened 174 NICU subjects, of whom 148 met screening criteria from January 29, 2019, to September 18, 2020. Daily SCr and urine samples were obtained for up to 7 days of NTM exposure plus 2 days after exposure ended or end of AKI. AKI was defined by a SCr rise of 50% from baseline. The highest uNGAL obtained was evaluated to determine its relationship to the diagnosis of AKI. Logistic regression models were used to determine optimal uNGAL cutoffs. Results: The negative predictive value of a uNGAL value ≥250 ng/mL was 96.8% (95% CI = 93.3–100%). Urine NGAL ≥400 ng/mL demonstrated the highest ROC-AUC value of 0.72 with a positive likelihood risk for AKI of 2.76 (1.39–4.13). Discussion/Conclusion: We propose that uNGAL could be used to screen for NTM-AKI and thus replace many blood draws needed in those exposed to NTM. The ideal uNGAL threshold requires further investigation in infants.

Predictors of oliguria in post-traumatic acute kidney injury

BackgroundAcute kidney injury is classified by urine output into non-oliguric and oliguric variants. Non-oliguric acute kidney injury has lower morbidity and mortality and accounts for up to 64% of acute kidney injury in hospitalized patients. However, the incidence of non-oliguric acute kidney injury in the trauma population and whether the 2 variants of acute kidney injury share the same risk factors is unknown. We hypothesized that oliguria would be present in the majority of acute kidney injury in severely injured trauma patients and that unique risk factors would predispose patients to the development of oliguria. MethodsPatients admitted to the trauma intensive care unit and diagnosed with an acute kidney injury between 2016 to 2021 were identified. Cases were categorized based on urine output into oliguric (<400 mL per day) and non-oliguric (>400 mL per day) disease. Risk factors, management, and outcomes were compared. Logistic regression was used to identify risk factors associated with oliguria. ResultsA total of 227 patients met inclusion criteria. Non-oliguric acute kidney injury accounted for 74% of all cases and was associated with greater survival (78% vs 35.6%, P < .001). Using logistic regression, female sex, vasopressor use, and a greater net fluid balance at 48 hours were all predictive of oliguria (while controlling for age, race, shock index, massive transfusion, operative intervention, cardiac arrest, and nephrotoxic medication exposure). ConclusionNon-oliguria accounts for the majority of post-traumatic acute kidney injury and is associated with improved survival. Specific risk factors for the development of oliguric acute kidney injury include female sex, vasopressor use, and a higher net fluid balance at 48 hours.

Reduction of acute kidney injury in pediatric patients after bone marrow transplant: A prospective analysis after quality improvement implementation.

371 Background: Hematopoietic cell transplantation (HCT) is a curative therapy for malignant and non-malignant diseases. Acute kidney injury (AKI) is a common complication after HCT secondary to use of nephrotoxic medications (NTMx) prescribed for conditioning and prophylaxis. A recently published meta-analysis estimates the incidence of AKI after HCT to be 55.1%, with Stage 3 occurring in 8.3% of patients. Nephrotoxic medication–associated AKI (NAKI) affects 19%–31% of children who receive an intravenous aminoglycoside, with NAKI rates doubling with receipt of ≥ 3 nephrotoxic medications on the same day. We hypothesized that reducing NTMx exposure in pediatric HCT patients would be associated with lower all causes AKI incidence in the HCT unit. Methods: Single-center harm-preventing measures have been implemented at our center since 2019 to 2023. A multi-phased approach was used to increase education and recognition surrounding NTMx exposures in the HCT unit and role in subsequent AKI. We identified champions in the Pediatric HCT and Infectious Disease Host Defense teams. Five educational sessions took place from November 2022-June 2023 and an informational handout was created and distributed to HCT providers. Notifications to attending physicians of patients meeting NTMx exposure criteria, with acceptable alternatives to commonly used nephrotoxic drugs, and suggestions for AKI monitoring took place during daily rounds by the clinical pharmacist. Data on exposures and NAKIs’ was collected and reviewed every 3 months. Results: The cohort included 79 unique patients with 3547 patient days admitted to the HCT unit at Nationwide Children’s Hospital between January 1 2022 and March 31 2023. A total of 210 NTMx exposures were identified and resulted in 22 NAKI events. We reduced the rates of nephrotoxic medication exposure by 51% from 14.36 to 7 per month per 1000 patient days and NAKIs by 21% from to 1.27 to 1 per month per 1000 patient days since the start of our interventions. Conclusions: Successful interventions to decrease AKI in patients admitted to the HCT unit require a multi-disciplinary, iterative, and continuous approach, including recurrent education efforts to providers and pharmacy-driven daily physician alerts. Organizational implementation of these interventions is still ongoing.

Artificial intelligence in early detection and prediction of pediatric/neonatal acute kidney injury: current status and future directions.

Acute kidney injury (AKI) has a significant impact on the short-term and long-term clinical outcomes of pediatric and neonatal patients, and it is imperative in these populations to mitigate the pathways leading to AKI and be prepared for early diagnosis and treatment intervention of established AKI. Recently, artificial intelligence (AI) has provided more advent predictive models for early detection/prediction of AKI utilizing machine learning (ML). By providing strong detail and evidence from risk scores and electronic alerts, this review outlines a comprehensive and holistic insight into the current state of AI in AKI in pediatric/neonatal patients. In the pediatric population, AI models including XGBoost, logistic regression, support vector machines, decision trees, naïve Bayes, and risk stratification scores (Renal Angina Index (RAI), Nephrotoxic Injury Negated by Just-in-time Action (NINJA)) have shown success in predicting AKI using variables like serum creatinine, urine output, and electronic health record (EHR) alerts. Similarly, in the neonatal population, using the "Baby NINJA" model showed a decrease in nephrotoxic medication exposure by 42%, the rate of AKI by 78%, and the number of days with AKI by 68%. Furthermore, the "STARZ" risk stratification AI model showed a predictive ability of AKI within 7days of NICU admission of AUC 0.93 and AUC of 0.96 in the validation and derivation cohorts, respectively. Many studies have reported the superiority of using biomarkers to predict AKI in pediatric patients and neonates as well. Future directions include the application of AI along with biomarkers (NGAL, CysC, OPN, IL-18, B2M, etc.) in a Labelbox configuration to create a more robust and accurate model for predicting and detecting pediatric/neonatal AKI.

Gestational age-specific clinical correlates of acute kidney injury in preterm infants with necrotizing enterocolitis.

To study the gestational age-specific risk factors and outcomes of severe acute kidney injury (AKI) in neonates with necrotizing enterocolitis (NEC). Retrospective cohort study comparing gestational age (GA)-specific clinical data between infants without severe AKI (stage 0/1 AKI) and those with severe AKI (stages 2 and 3 AKI) stratified by GA ≤27 and >27 weeks. Infants with GA ≤27 weeks had double the rate of severe AKI (46.3% vs. 20%). In infants with GA >27 weeks, male sex, outborn, and nephrotoxic medication exposure were associated with severe AKI. On multivariable logistic regression, in infants with GA ≤27 weeks, surgical NEC (OR 35.08 (CI 5.05, 243.73), p < 0.001) and ostomy (OR 6.2(CI 1.29, 29.73), p = 0.027) were associated with significantly higher odds of severe AKI. Surgical NEC infants with GA >27 weeks and severe AKI were significantly more likely to be outborn, have later NEC onset, need dopamine, and have longer hospitalization (158 days [110; 220] vs.75.5 days [38.8; 105]; p = 0.007 than those with non-severe AKI. In neonates with NEC, surgical intervention was associated with moderate-to-severe AKI in infants with GA ≤27 weeks and with longer hospitalization in infants with GA >27 weeks. In both cohorts need for surgery, stoma, cholestasis, and mechanical ventilation were associated with severe AKI; however, the infants with GA <27 weeks had twice the risk of severe AKI than GA >27 weeks group. The longer exposure to nephrotoxic medication and referral need were significant risk factors for AKI in GA >27 weeks group. GA-specific kidney protective and monitoring strategies to prevent AKI and its consequences are needed to improve the clinical outcomes in neonates with NEC. Understanding the risk factors and short- and long-term outcomes unique to different GA groups will help inform those strategies.

Risk of chronic kidney disease in children who developed acute kidney injury secondary to nephrotoxic medication exposure in infancy

Introduction Nephrotoxic medication (NTM) is one of the common causes of acute kidney injury (AKI) in critically ill infants. Current knowledge about the long-term effects of NTM exposure and associated AKI during the neonatal period and early infancy is limited. Hence, we aimed to explore the risk of chronic kidney disease (CKD) after NTM-AKI in this age group. Methods We performed a cross-sectional study including children 2–7 years of age, who had a history of high NTM exposure during NICU hospitalization. Cases and controls were defined as children who developed AKI and who did not develop AKI after NTM exposure, respectively. The primary outcome of interest was to explore the prevalence of composite CKD. In addition, we explored differences in urinary biomarker kidney injury molecule-1 (KIM-1) between the groups. Results We enrolled 48 children, 18 cases and 30 controls in which 25/48 (52%) had at least one finding of CKD. The composite CKD outcome tended to be higher in cases vs controls (61.1% vs. 46.6%, odds ratio = 1.79 (95% confidence interval 0.54-5.8)); however, this was not statistically significant. Median urinary KIM-1 value trended higher in controls, 0.367(0.23-0.59) vs. 0.20 (IQR 0.11-0.47), which was not statistically significant. Conclusion In this study, 52% of children exposed to NTM had at least one marker of CKD at a median age of 5 years. Multicenter, large prospective studies are needed to improve our understanding of the natural course of NTM-AKI and to determine risk factors and strategies to reduce CKD in this high-risk population.

Indoxyl sulfate influences susceptibility of proximal tubule epithelial cells to gentamicin cytotoxicity

Background: Patients with chronic kidney disease (CKD) are at increased risk of acute kidney injury (AKI) following exposure to nephrotoxic medications such as gentamicin, which can accelerate the progression of CKD. Therefore, there is a critical need to understand the molecular pathogenesis of acute-on-chronic kidney disease. A hallmark of CKD is the systemic bioaccumulation of uremic solutes, such as the tryptophan metabolite indoxyl sulfate (IS). Accumulating evidence suggests that IS has direct effects on the kidneys that contribute to CKD progression, and the objective of this study was to the determine the effect of IS on proximal tubule epithelial cell (PTEC) and test the hypothesis that IS exposure increases susceptibility to gentamicin-induced cytotoxicity. Methods: Cultured immortalized PTECs (HK-2 cells) were treated with IS and gentamicin at varying concentrations, and cell viability was assessed using the Trypan blue and MTT assays. TMT proteomic profiling with IBAQ quantitation and gene set enrichment analysis was used to identify differentially abundant proteins and cellular processes and pathways that are dysregulated by IS exposure and could mediate the cytotoxic effects of IS and influence susceptibility to gentamicin cytotoxicity. Results: Treatment with 100 μM IS had a modest cytotoxic effect (15-20% cell death after 24 hours over multiple experiments). Proteomic profiling of HK-2 cells identified 10,030 proteins, and IS treatment induced changes in the abundance of 60 proteins, including increased expression of kidney injury molecule-1, an established biomarker of PTEC injury, and VCAM-1, a marker of maladaptive repair after AKI. In contrast, expression of mitochondrial complex V ATPase F o subunits C1, C2, and C3 and mitochondrial ribosomal proteins L18 and L50 were down regulated, and GSEA found that there was an overall decrease in mitochondrial translation following IS exposure. These results suggest that IS is directly cytotoxic to PTECs and negatively impacts mitochondrial dynamics and cellular respiration. Pretreatment with IS increased susceptibility of HK-2 cells to 10 mM gentamicin cytotoxicity as assessed by Trypan blue staining (30.1% +/- 6.4% cells stained positive without IS pretreatment vs 46.1 +/- 3.1% with IS pretreatment, p &lt; 0.001), and this effect was confirmed using the MTT assay. Conclusion: IS has direct cytotoxic effects on PTECs and increases their susceptibility to gentamicin cytotoxicity, and systemic bioaccumulation of IS in CKD could therefore predispose to subsequent AKI following nephrotoxic medication exposure. This phenomenon could be mediated IS-induced downregulation of mitochondrial gene translation associated with dysregulated mitochondrial dynamics and impaired cellular respiration. This study was supported by the George M. O'Brien Kidney Translational Core Center at the University of Michigan (subaward of 5P30-DK081943 14). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Neonatal nephrotoxic medication exposure and early acute kidney injury: results from the AWAKEN study.

We aimed to describe nephrotoxic medication exposure and investigate associations between exposure and acute kidney injury (AKI) in the neonatal intensive care unit during the first postnatal week. Secondary analysis of the AWAKEN cohort. We evaluated nephrotoxic medication exposure during the first postnatal week and associations with AKI using time-varying Cox proportional hazard regressions models.Nephrotoxic medication exposure categories were defined as: no nephrotoxic medication, nephrotoxic medications excluding aminoglycosides, aminoglycoside alone, and aminoglycoside and another nephrotoxic medication. Of 2162 neonates, 1616 (74.7%) received ≥1 nephrotoxic medication. Aminoglycoside receipt was most common (72%). AKI developed in 211(9.8%) neonates and was associated with a nephrotoxic medication exposure (p < 0.01). Nephrotoxic medicationexposures including a nephrotoxic medication excluding aminoglycoside (aHR 3.14, 95% CI 1.31-7.55) and aminoglycoside and another nephrotoxic medication (aHR 4.79, 95% CI 2.19-10.50) were independently associated with AKI and severe AKI (stage 2/3), respectively. Nephrotoxic medication exposure in critically ill infants is common during the first postnatal week. Specific nephrotoxic medication exposure, principally aminoglycosides with another nephrotoxic medication, are independently associated with early AKI.

Risk factors for development of acute kidney injury and acute kidney disease in critically ill children.

Acute kidney injury (AKI) is common among critically ill children and these children are at risk of developing acute kidney disease (AKD). A prospective cohort study was conducted on children aged > 1month to ≤ 18years old admitted to the pediatric intensive care unit (ICU) of Hong Kong Children's Hospital from 6/2020 to 6/2021. The incidences and risk factors of both AKI and AKD were determined. There were 254 eligible admissions (58.3% inmales, with a median age of 4.9 [9.7] years). The overall AKI incidence was 41.7% and 56% of children who remained hospitalized inthe pediatric ICU for ≥ 7days after acquiring AKI developed AKD. Cardiac surgery, bone marrow transplantation and requirement of inotropes were risk factors for both AKI and AKD. The requirement of non-invasive ventilation [relative risk (RR): 2.625 (1.361, 5.064)], total medication dose [RR 1.006 (1.002, 1.010)] and maximal medication intensity [RR 1.154 (1.038, 1.283)] were additional determinants of AKI. Factors indicating more severe AKI and AKI progression were predictive of AKD development. The overall mortality in the pediatric ICUwas 3.1%. AKI was significantly associated with mortality (p < 0.001), longer length of hospitalization in the pediatricICU (p < 0.001) and hospital stay (p < 0.001). AKD was associated with a lower estimated glomerular filtration rate at dischargefrom the pediatric ICU (p = 0.036). AKI and AKD were common among critically ill children, and were associated with significant morbidity and mortality. Few modifiable risk factors, especially those related to nephrotoxic medication exposure, were associated with AKI development and AKD progression.

452 - Neoatal nephrotoxic medication exposure and early acute kidney injury: Results from the AWAKEN study

452 - Neoatal nephrotoxic medication exposure and early acute kidney injury: Results from the AWAKEN study

Decreases in Nephrotoxic Pain Medications Are Not Associated With Increased Opioid Utilization in Critically Ill Children.

Quality improvement initiatives to decrease rates of nephrotoxic medication exposure have reduced rates of acute kidney injury (AKI) in noncritically ill children. The objective of our study was to analyze the implementation of a similar program in critically ill children and to measure important balancing measures including opioid and benzodiazepine exposure. Prospective quality improvement study. PICU at Children's Hospital Colorado between 2018 and 2020. All children admitted to PICU. Quality improvement initiative called Nephrotoxic Injury Negated by Just-In-Time Action (NINJA). Eight thousand eight hundred thirty-three PICU patient admissions were included. Mean rates of nephrotoxic medication exposure/1,000 PICU patient days decreased from 46 to 26, whereas rates of nephrotoxic AKI/1,000 PICU patient days did not change. Nonsteroidal anti-inflammatory drug dispenses per 1,000 patient days were reduced from 521 to 456. Similarly, opioid and benzodiazepine exposures per 1,000 patient days were reduced from 812 to 524 and 441 to 227, respectively, during the study observation period. The NINJA intervention was efficaciously implemented in our single-center PICU. Nephrotoxic exposure is a modifiable factor that did not inadvertently increase exposure to opioids and benzodiazepines.

Association between nitric oxide synthase 3 genetic variant and acute kidney injury following pediatric cardiac surgery

Acute kidney injury (AKI) complicates 30% to 50% of cardiac surgeries in pediatric patients. Genetic variants that affect renal blood flow and inflammation have been associated with AKI after cardiac surgery in diverse populations of adults but have not been studied in children. The objective of this study is to test the hypothesis that common candidate genetic variants are associated with AKI following pediatric cardiac surgery. This is a retrospective cohort study at a single tertiary referral children's hospital of 2,062 individual patients undergoing surgery for congenital heart disease from September 2007 to July 2020. Pre-specified variants in candidate genes (AGTR1, APOE, IL6, NOS3, and TNF) were chosen. AKI was defined using Kidney Disease: Improving Global Outcomes serum creatinine criteria in the first week following surgery. Outcomes were analyzed by univariate and multivariable analysis of demographic, clinical, and genetic factors. The study population had median age of 6 (interquartile range [IQR], 1-53) months, 759 (37%) of whom met criteria for postoperative AKI. In unadjusted analyses of each genetic variant, only NOS3 (rs2070744) was associated with lower risk for AKI (OR 0.75, 95% CI 0.62-0.9, P=.002). In logistic regression analyses adjusting for body surface area, previously identified genetic syndrome, Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) score, cardiopulmonary bypass time, and nephrotoxic medication exposure, the NOS3 variant remained protective against AKI (OR 0.7, 95% CI 0.58-0.85, P<.001). A common variant in NOS3 is associated with decreased incidence of AKI in children undergoing cardiac surgery. Further analysis of the genetic contributions to postoperative AKI may help identify individual risk in the pediatric population.

Neonatal Acute Kidney Injury.

Acute kidney injury (AKI) is a common occurrence in the neonatal intensive care unit (NICU). In recent years, our knowledge of the incidence and impact of neonatal AKI on outcomes has expanded exponentially. Neonatal AKI has been shown to be associated with adverse outcomes including increased length of mechanical ventilation, prolonged length of stay, and rise in mortality. There has also been increasing work suggesting that neonates with AKI are at higher risk of chronic kidney disease (CKD). In the past, AKI had been defined multiple ways. The utilization of the neonatal modified Kidney Disease: Improving Global Outcomes (KDIGO) criteria as the standard definition for neonatal AKI in research and clinical care has driven the advances in our understanding of neonatal AKI over the last 10 years. This definition has allowed researchers and clinicians to better understand the incidence, risk factors, and outcomes associated with neonatal AKI across populations through a multitude of single-center studies and the seminal, multicenter Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study. As the impacts of neonatal AKI have become clear, a shift in efforts toward identifying those at highest risk, protocolizing AKI surveillance, improving prevention and diagnosis, and expanding kidney support therapy (KST) for neonates has occurred. These efforts also include improving risk stratification (identifying high risk populations, including those with nephrotoxic medication exposure) and diagnostics (novel biomarkers and diagnostic tools). Recent work has also shown that the targeted use of methylxanthines may prevent AKI in a variety of high-risk populations. One of the most exciting developments in neonatal AKI is the advancement in technology to provide KST to neonates with severe AKI. In this comprehensive review we will provide an overview of recent work and advances in the field of neonatal AKI. This will include a detailed review of (1) the definition of neonatal AKI, (2) the epidemiology, risk factors, and outcomes associated with neonatal AKI, (3) improvements in risk stratification and diagnostics, (4) mitigation and treatment, (5) advancements in the provision of KST to neonates, and (6) the incidence and risk of subsequent CKD.

Long-Term Healthcare Cost Savings of a Pediatric Nephrotoxic Medication-Associated Acute Kidney Injury Reduction Program in a Simulated Sample

Background: Nephrotoxic medication exposure is a common cause of acute kidney injury (AKI) in hospitalized children and is associated with chronic kidney disease (CKD). The pharmacist-reliant NINJA program reduced nephrotoxic medication exposure and associated AKI. Objectives: We assess potential healthcare cost savings from reduced CKD by preventing AKI with the NINJA program for a pediatric population through age 21. Methods: We simulated a cohort of 1000 hospitalized non-critically ill children. From the published literature, 310 develop AKI, 267 survive to 6 months, and 10-70% develop CKD, and NINJA implementation reduced AKI by 23.8%. Allowing for varying CKD rates, we estimated a range of NINJA’s savings. We assumed an annual GFR decline of 1.2 (noHTN) ml/min/1.73 m2 for half the sample and 1.7 (HTN) ml/min/1.73 m2 for the other half to account for CKD progression without and with hypertension (HTN). We model attributable costs including CKD stage-related medications and outpatient visits/tests in 2018 dollars discounted at 3%. We subtract the cost of NINJA screening (daily serum creatinine and pharmacist time) from net savings. We exclude end-stage renal disease (ESRD) and hospitalization costs. Results: No intervention estimated CKD related costs are $761,852 to $5,735,027. Post-NINJA cost decreases to $616,086 to $4,312,183 (net savings: $145,766 to $1,422 183). Total savings, accounting for NINJA screening ($256,680) are -$110,914 to $1,1 165 503. The breakeven AKI to CKD conversion rate is 13-14% with growth hormone cost included, and 64-65% without. Conclusion: The NINJA program is likely cost beneficial, with greater savings into adulthood by avoiding/delaying ESRD and its costs.

Association of kidney function with posterior reversible encephalopathy syndrome in children.

Aims: Investigate if kidney function markers predict posterior reversible encephalopathy syndrome (PRES) in children. Materials and methods: In a case-control study of high-risk children with confirmed PRES (n = 35) compared to controls (n = 14), we recorded blood urea nitrogen (BUN), serum creatinine, serum albumin, hemoglobin concentrations, estimated glomerular filtration rate, and documentation of acute kidney injury (AKI). We applied multivariable regression models and determined receiver operating characteristic curves. Results: Mean age was 9.5 (SD 4.9) years, 51% were female, 29% had chronic kidney disease, 67% had nephrotoxic medication exposure, and 29% had AKI. A 1-mg/dL increase in BUN (adjusted OR 1.03, 95% CI 0.99 – 1.07) and AKI (adjusted OR 3.78, 0.68 – 21.13) were minimally, but not statistically significantly, associated with PRES. BUN = 21.6 mg/dL performed best but had low ability to predict PRES (area under the curve 0.664, 0.498 – 0.831), with 60.0% sensitivity, 71.4% specificity, and positive and negative predictive values of 84.0% and 41.7%, respectively. Conclusion: Kidney function may be a relatively more minor risk factor for PRES than previously believed. Further prospective studies with larger sample sizes and better kidney function assessments are warranted to evaluate the role of kidney function in the development of PRES.

Outpatient Nephrotoxic Medication Prescription after Pediatric Intensive Care Acute Kidney Injury.

Background: Nephrotoxic medication (NTM) avoidance may prevent further kidney damage in children with acute kidney injury (AKI). We compared outpatient NTM prescriptions in children with or without AKI during pediatric intensive care (PICU) hospitalization. We hypothesize that children with AKI are prescribed NTMs at the same rate as those without it. Methods: This was a retrospective administrative data study of children <18 years, admitted to two PICUs in Montreal, Canada, from 2003 to 2005, with ≥30 days of provincial drug coverage. We evaluated the presence of ≥3 outpatient NTM prescriptions during the first year and 5 years after PICU discharge. Results: Of 970 children, 23% had PICU AKI. In the 1st–5th years after discharge, 18% AKI vs. 10% non-AKI and 13% AKI vs. 4% non-AKI patients received ≥3 NTM prescriptions, respectively. There was no association between PICU AKI and prescription of ≥3 NTMs during the first year (adjusted RR 1.02 [95% CI 0.95–1.10]) nor in the first 5 years post-discharge (adjusted RR 1.04 [95%CI 0.96–1.12]). Conclusions: By offering a better understanding of the current state of outpatient NTM prescription to children with AKI, our study is a step toward considering strategies such as knowledge translation interventions for decreasing NTM exposure and improving outcomes in children with AKI.

Use of the NINJA (Nephrotoxic Injury Negated by Just-in-Time Action) Program to Identify Nephrotoxicity in Pediatric Patients with Cystic Fibrosis.

This study aims to use and evaluate the Nephrotoxic Injury Negated by Just-in-time Action (NINJA) program in hospitalized patients with cystic fibrosis (CF) at Children's Healthcare of Atlanta. This was a single-center study evaluating patients with CF who were hospitalized and admitted to the pulmonary service 4 months pre- and post-NINJA implementation. Postimplementation patients with high nephrotoxic medication (NTMx) exposure were identified using an electronic reporting tool that triggered the pharmacist to alert the medical team and recommend Monday/Wednesday/Friday serum creatinine (SCr) monitoring. High NTMx exposure was defined as 3 or more NTMxs given concurrently, or at least 3 consecutive days of IV aminoglycosides or vancomycin. Outcomes assessed were rate of SCr monitoring, NTMx exposure, and days of acute kidney injury (AKI) pre- and post-NINJA implementation. A total of 19 patients and 25 high-NTMx exposures were identified both pre- and post-NINJA implementation. The SCr monitoring increased from 13% to 50% of NTMx exposure days in the pre- versus post-NINJA time frame. More NTMx exposure days occurred in the post-NINJA time frame, from 250 exposure days per 1000 patient days pre-NINJA to 521 post-NINJA. An increased incidence of AKI events and AKI days were noted post-implementation; however, these differences were not significantly different between the 2 groups. Increased SCr monitoring for patients with NTMx exposure using NINJA uncovered more episodes of AKI. Increased prevalence of NTMx use was associated with increased rates of AKI. Increased SCr monitoring as a result of NINJA implementation may allow for earlier detection of AKI.

The Effect of a Short Course of Tocolytic Indomethacin on Urinary Biomarkers in Premature Infants.

The aim of this study was to determine the effects of a 2-day prenatal course of indomethacin on the premature kidney as reflected by serum creatinine and urinary biomarkers. Urine of infants ≤32 weeks was collected for the first 14 days and analyzed for cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, β2 microglobulin, epidermal growth factor, uromodulin, and microalbumin. Bivariate analysis compared serum creatinine and biomarkers of exposed (INDO) and unexposed (CONT) subjects. Fifty-seven infants (35 CONT and 22 INDO) were studied. The cohorts were similar in gestational age, birthweight, race, gender, nephrotoxic medication exposure, and Apgar's scores. CONT had more dopamine exposure and included more pre-eclamptic mothers (p = 0.005). No difference in creatinine-based acute kidney injury or the log transformed mean, maximum, and minimum values of urinary biomarkers was detected. Our findings suggest that a short course of tocolytic indomethacin does not result in neonatal acute kidney injury. · A short prenatal course of indomethacin does not result in neonatal acute kidney injury (AKI).. · Urinary EGF might have a promising role as a more sensitive biomarker for early detection of AKI in premature infants..