Nephrotoxic Medications Research Articles

Kidney Injury in Children after Hematopoietic Stem Cell Transplant

Hematopoietic cell transplant (HCT), used for treatment of many malignant and non-malignant pediatric diseases, is associated with serious complications, limiting this therapy's benefit. Acute kidney injury (AKI), seen often after HCT, can occur at different stages of the transplant process and contributes to morbidity and mortality after HCT. The etiology of AKI is often multifactorial, including kidney hypoperfusion, nephrotoxicity from immunosuppressive and antimicrobial agents, and other transplant-related complications such as transplant-associated thrombotic microangiopathy and sinusoidal obstructive syndrome. Early recognition of AKI is crucial to prevent further AKI and associated complications. Initial management includes identifying the etiology of AKI, preventing further kidney hypoperfusion, adjusting nephrotoxic medications, and preventing fluid overload. Some patients will require further support with kidney replacement therapy to manage fluid overload and AKI. Biomarkers of AKI, such as neutrophil gelatinase-associated lipocalin can aid in detecting AKI before a rise in serum creatinine, allowing earlier intervention. Long-term kidney dysfunction is also prominent in this population. Therefore, long-term follow-up and monitoring of renal function (glomerular filtration rate, microalbuminuria) is required along with management of hypertension, which can contribute to chronic kidney disease.

Clinical characteristics and outcomes of community acquired-acute kidney injury.

Published works have reported the impact of a nephrologist intervention on outcomes for patients with hospital-acquired acute kidney injury (HA-AKI), however little is known about the clinical characteristics of patients with community-acquired acute kidney injury (CA-AKI) and the impact of nephrology interventions on outcomes in these patients. A retrospective study on all adult patients admitted to a large tertiary care hospital in 2019 who were identified to have CA-AKI were followed from hospital admission to discharge. Clinical characteristics and outcomes of these patients were analysed by receipt of nephrology consultation. Statistical analysis included descriptive, simple Chi-squared/Fischer Exact test, independent samples t-test/Mann-Whitney U test and logistic regression. 182 patients fulfilled the study inclusion criteria. Mean age was 75 ± 14years, 41% were female, 64% had stage 1 AKI on admission, 35% received nephrology input and 52% had achieved recovery of kidney function by discharge. Higher admission and discharge serum creatinine (SCr) (290.5 vs 159 and 173 vs 109µmol/L respectively, p = < 0.001), and younger age (68 vs 79, p = < 0.001) were associated with nephrology consultations, whilst length of hospitalisation, mortality and rehospitalisation rates were not significantly different between the two groups. At least 65% were recorded to be on at least one nephrotoxic medication. Our findings provide a snapshot of current practice where close to two-thirds of hospitalised patients with CA-AKI had a mild form of AKI that was associated with good clinical outcomes. While higher SCr on admission and younger age were predictors of receiving a nephrology consultation, nephrology consultations did not have any impact on outcomes.

A Study on etiology and outcome of acute kidney injury patients requiring haemodialysis in a rural tertiary medical college hospital, Kishoreganj

Background and objectives: AKI is an increasingly common complication of critical illness, with some researches showing that as high as 1 in 5 adults and 1 in 3 children experiencing AKI per hospital admission. Whether occurring in the community or in the hospital, the clinical and public health importance of AKI is well established due to the association with high mortality and its separate independent effect on the risk of death and resource use. This study was aimed to find out the etiology and outcome of acute kidney injury patients requiring haemodialysis.&#x0D; Methods: A retrospective study was done on 70 patients of AKI who required haemodialysis support in dialysis unit of medicine department of Jahurul Islam Medical College Hospital, Kishoreganj during the time period from Jan - 2018 to Dec – 2020. All patients of age 13 and above with AKI and have been dialyzed at least once during the study period were included.&#x0D; Results: In this study, there was an overall male preponderance (70%) with age range of 13-40 years (48.57%). Most common features of presentation were oliguria, cough, respiratory distress, drowsiness, disorientation, reddish urine, pedal edema, fever and high blood pressure. The most common causes of AKI were sepsis (30%), hypovolemia (21.42%), acute glomerulonephritis (AGN) (14.29%) and pregnancy related causes (10%). Common indications for haemodialysis of AKI patients were refractory fluid overload (70%), features of uraemic encephalopathy (22.86%). In this study, 78.57% of AKI patients requiring haemodialysis were improved and discharged, 08.57% patients were progressed to end stage renal disease, 07.15% patients were expired and 05.71% patients were absconded.&#x0D; Conclusion: It is concluded that sepsis, hypovolemia, AGN, obstetric causes, surgical causes and nephrotoxins were the primary causes of AKI patients requiring haemodialysis in this study. Most of these causes can be prevented with simple interventions such as appropriate management of infections, health education on oral rehydration, quality prenatal and emergency obstetric care and taking appropriate precautions when prescribing potentially nephrotoxic medications. Majority of the patients of AKI with complications were improved with haemodialysis. So, expansion of haemodialysis services to all parts of the country is necessary.&#x0D; AKMMC J 2021; 12(2): 98-103

Reducing incidence of postoperative acute kidney injury in trauma and orthopaedics patients: a quality improvement project

BackgroundAcute kidney injury (AKI) is a common postoperative complication which increases morbidity and mortality. This quality improvement project aimed to implement measures targeting known risk factors to decrease the incidence...

A Retrospective Analysis of Risk Factors and Impact of Acute Kidney Injury in Critically Ill Children.

Acute kidney injury (AKI) is a serious clinical condition in critically ill children and is associated with worse outcomes. A few pediatric studies focused on the risk factors of AKI. We aimed to identify the incidence, risk factors, and outcomes of AKI in the pediatric intensive care unit (PICU). All the patients admitted to PICU over a period of 20 months were included. We compared both groups the risk factors between AKI and non-AKI. A total of 63 patients (17.5%) of the 360 patients developed AKI during PICU stay. The presence of comorbidity, diagnosis of sepsis, increased PRISM III score, and positive renal angina index were found to be risk factors for AKI on admission. Thrombocytopenia, multiple organ failure syndrome, the requirement of mechanical ventilation, use of inotropic drugs, intravenous iodinated contrast media, and exposure to an increased number of nephrotoxic drugs were independent risk factors during the hospital stay. The patients with AKI had a lower renal function on discharge and had worse overall survival. AKI is prevalent and multifactorial in critically sick children. The risk factors of AKI may be present on admission and during the hospital stay. AKI is related to prolonged mechanical ventilation days, longer PICU stays, and a higher mortality rate. Based on the presented results early prediction of AKI and consequent modification of nephrotoxic medication may generate positive effects on the outcome of critically ill children.

Prenatal use of indomethacin for preterm labor and renal function among very low birth weight infants.

Indomethacin is administered as a tocolytic agent for threatening preterm labor <28weeks of gestation. Only a few, not conclusive, studies have investigated its nephrotoxicity in very low birth weight (VLBW) infants. We investigated whether indomethacin increases the incidence of acute kidney injury (AKI) among VLBW infants. This is a retrospective study including all VLBW infants born at our center between January 1, 2005, and December 31, 2013. Indomethacin was administered to women with preterm labor and intact membranes. Neonatal AKI was defined according to KDIGO classification. Univariate analyses were performed comparing VLBW infants exposed to and not exposed to indomethacin. In the multivariable model, the association of indomethacin and AKI was adjusted for patent ductus arteriosus, use of nephrotoxic medications, birth weight, and gestational age. Five hundred seventy-five VLBW infants were included, 49 (8.5%) of whom were exposed to indomethacin in utero. The univariate analysis showed that infants exposed to indomethacin had lower birth weight, lower gestational age, and higher incidence of AKI than infants not exposed. The multivariable model adjusted for confounding factors confirmed an increased risk of AKI in relation to gestational age at birth <27 weeks, but not to indomethacin. Our data suggest that extreme prematurity, but not the use of indomethacin, is associated with AKI.

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

609: NEPHROTOXIC MEDICATIONS AND THEIR ASSOCIATION WITH ACUTE KIDNEY INJURY IN CRITICALLY ILL CHILDREN

Introduction: The incidence of developing acute kidney injury (AKI) in the pediatric intensive care unit (PICU) is estimated to be 26% (Kaddourah, 2017). Nephrotoxic medications are a modifiable risk factor associated with AKI in non-critically ill children & neonates (Moffett, 2011 & Stoops, 2019). The primary objective of this study is to evaluate the association between the number of nephrotoxic medications and the risk of developing AKI in critically ill children. Methods: This is a single center retrospective cohort study of critically ill children admitted to a tertiary care PICU. Inclusion criteria was patients age 0-21 years admitted for >24 hours. Exclusion criteria was history of chronic kidney disease or if expired within 24 hours of admission. We considered the same list of medications used in previous studies to be nephrotoxic, NSAIDs, certain antibiotics, and chemotherapy agents. AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria including serum creatinine increase by ≥0.3, >1.5 times baseline, or urine output < 0.5 mL/kg/hr for ≥12 hours. Severe AKI was defined as Stage 2 & 3 AKI. Exposure to the number of nephrotoxic medications and development of AKI was analyzed. Results: 60 patients were analyzed. Median age was 6.55 (1.12-12.71) years and mostly male (55%). Median LOS was 3 (2-5) days. Majority had a respiratory illness as primary diagnosis (31%). Median PELOD2 score was 3.5 (2-7). Incidence of AKI was 40%. 46% of patients who developed AKI did not have any nephrotoxic medications administered. 42% of patients with AKI were administered 1 nephrotoxic medication. 12% of patients with AKI had exposure to ≥2 medications. Amongst all patients with AKI, 88% had severe AKI. The most common medications administered were ibuprofen (22%) and vancomycin (17%). Exposure to the number of nephrotoxic medications and development of AKI was assessed with Fisher’s Exact test. There was no statistical significance with the number of nephrotoxic medications and the development of AKI (p=0.962). Correlation analysis revealed an increased rate of AKI with PICU LOS ≥5 days (p=0.029). Conclusions: There was no statistically significant association between the number of nephrotoxic medications and the development of AKI. Patients with longer LOS had a higher risk of developing AKI.

610. Low Rates of Acute Kidney Injury (AKI) in Outpatient Vancomycin Managed by Pharmacists using Precision Dosing Software

Abstract Background AKI is a complication of intravenous vancomycin (VAN) occurring in up to 43% of patients (pts) during hospitalization. Data on AKI in pts receiving VAN through outpatient parenteral antimicrobial therapy (OPAT) are limited. There is suggestion that VAN managed through precision dosing pharmacokinetic (PK) software may limit this occurrence. We evaluated the AKI rate of pts receiving VAN as OPAT through Physician Office Infusion Centers (POICs) over a 12-month period. Methods A review was conducted of OPAT VAN pts treated in 2021 with therapeutic drug monitoring (TDM) performed (InsightRX) and ≥2 VAN serum levels. These pts were then evaluated for AKI, defined as increase in serum creatinine (SCr) ≥1.5 times baseline. Pts on dialysis were excluded. Data included comorbidities, diagnosis, VAN regimen, concomitant medications, SCr, and VAN serum levels. PK parameters were collected with trough values and estimated 24-hr area under the curve (AUC24). Outcome of therapy was assessed following identification of AKI. Results A total of 330 pts from 51 POICs had TDM performed. Of these, 27 (8.2%) developed AKI. Median age was 61 years, 67% were male, and baseline SCr was 0.8 mg/dL (IQR, 0.7-1.0). Most pts (89%) were on concomitant nephrotoxic medications. Median duration of OPAT was 34 days (IQR, 18-41) with onset of AKI after 16 days (IQR, 10-21). At time of AKI, the median SCr increase was 1.7 times baseline (IQR, 1.5-2.0) with a corresponding VAN trough of 21 mg/mL (IQR, 15-28) and AUC24 of 572 mg*h/L (IQR, 495-660). As a result, VAN was discontinued in 14 (52%), dose or frequency modified in 10 (37%) with completion of VAN, and no modifications performed in 3 (11%). One pt who discontinued VAN required hospitalization due to AKI with resolution. Conclusion VAN managed by pharmacists in an OPAT setting using precision dosing software resulted in a low rate of AKI. Median rise in SCr was &amp;lt; 2 times baseline for those with AKI. Rapid identification of early AKI by the pharmacist resulted in changes to the regimen or VAN discontinuation, preventing serious patient sequelae. This supports the need for pharmacist-led monitoring in an outpatient setting with long VAN therapy durations. Disclosures Lucinda J. Van Anglen, PharmD, Merck &amp; Co.: Grant/Research Support|Paratek: Grant/Research Support.

Ferroptosis: A new insight for treatment of acute kidney injury.

Acute kidney injury (AKI), one of the most prevalent clinical diseases with a high incidence rate worldwide, is characterized by a rapid deterioration of renal function and further triggers the accumulation of metabolic waste and toxins, leading to complications and dysfunction of other organs. Multiple pathogenic factors, such as rhabdomyolysis, infection, nephrotoxic medications, and ischemia-reperfusion injury, contribute to the onset and progression of AKI. However, the detailed mechanism remains unclear. Ferroptosis, a recently identified mechanism of nonapoptotic cell death, is iron-dependent and caused by lipid peroxide accumulation in cells. A variety of studies have demonstrated that ferroptosis plays a significant role in AKI development, in contrast to other forms of cell death, such as apoptosis, necroptosis, and pyroptosis. In this review, we systemically summarized the definition, primary biochemical mechanisms, key regulators and associated pharmacological research progress of ferroptosis in AKI. We further discussed its therapeutic potential for the prevention of AKI, in the hope of providing a useful reference for further basic and clinical studies.

Abstract 13448: Time Course and Predictors of Renal Function Decline After Pediatric Heart Transplantation: A PHTS Multi-Institutional Analysis

Introduction: Decline in renal function can impact both the management and outcomes of pediatric heart transplantation (HTx). Initial renal function decline may be subclinical and underappreciated. We sought to identify the time course and predictors of decline in renal function and the impact of these changes on HTx outcomes. Methods: The Pediatric Heart Transplant Society (PHTS) database was queried to identify HTx recipients at participating centers from 1996 to 2019 with at least 1 year of follow-up. Patients with simultaneous or previous kidney transplant were excluded. Renal function was measured by modified Schwartz formula eGFR on annual follow-up forms and stratified into eGFR groups by National Kidney Foundation chronic kidney disease staging guidelines. “Initial renal function decline” was defined as the initial drop by at least one eGFR group relative to stage at 1 year post transplant (“baseline”). Results: Of the 5,250 patients who met inclusion criteria, initial renal function decline occurred, relative to baseline, in 7.4%, 18.7%, and 55.7%, by 1, 5, and 10 years of follow up, respectively (Figure A). eGFR group distribution for the cohort progressively worsened over the follow up period (Figure B). On multivariate Cox modeling, risk factors for renal function decline were increased BSA at 1 year post-transplant (HR 1.24 [1.02, 1.52]), acute rejection with hemodynamic compromise (HR 1.24 [1.10, 1.39]), and Black race (HR 1.21 [1.08, 1.36]) with the use of tacrolimus (vs cyclosporine) being protective (HR 0.77 [0.69, 0.85]). Patients whose eGFR was &lt; 30 mL/min at 1 year follow up had an increased risk of graft loss (P &lt; 0.0001 compared to all other groups). Conclusions: Decline in renal function occurs progressively, affecting over 50% of HTx recipients in long term follow up, independent of renal condition at the time of HTx. Avoidance of potentially nephrotoxic events and medications must be considered at all times in the long term management of pediatric HTx.

Medical students’ and health professionals’ knowledge regarding acute kidney injury: a cross-sectional study in the city of São Paulo, Brazil

Background Acute kidney injury (AKI) is a worldwide public health problem and is often treated by non-nephrologists. The objective of this study was to evaluate the knowledge of non-nephrologists, undergraduate medical students and health professionals regarding AKI. Methods An unsupervised and closed-response electronic questionnaire was sent to sixth-year medical students and non-nephrologist health professionals working in the city of São Paulo, Brazil. Results A total of 424 responses were returned from 650 invitations (40.1% males, 39.2% physicians, 34.0% senior medical students or resident physicians, 16.3% nurses and 10.6% pharmacists). The knowledge of medical students and health professionals about the prevalence and lethality of AKI in hospitals ranged from 40.8% to 59.2%. The most recognized susceptibilities and risk factors for AKI were sepsis/septic shock (95.0%) and diabetes mellitus (91.3%); the less-recognized susceptibilities and risk factors were exposure to gadolinium-based contrast (23.3%) and chronic liver disease (55.7%). The study participants’ rate of knowledge regarding the diagnosis of AKI was 50.9–73.6%, and their rate of knowledge regarding the criteria of increased serum creatinine and reduced urine volume was 52.6%. The most-recognized nephrotoxic medications were vancomycin (82.3%) and diclofenac (80.4%), and the least-recognized were acyclovir (34.0%) and cotrimoxazole (30.4%). The indications for emergency renal replacement therapy that were recognized by the study respondents were metabolic acidosis (82.3%), uremic syndrome (81.6%), hyperkalemia unresponsive to clinical treatment (78.1%) and acute pulmonary edema (71.6%). Conclusion The study showed knowledge gaps that can impact patient care and can be used to guide professional training programs.

Oral Acyclovir Induced Acute Kidney Injury

Acyclovir is an antiviral medication often used to treat outbreaks of herpes in children. Acyclovir has an exceptional safety profile; there is a possibility that it might induce severe nephrotoxicity in rare cases. In this report, we present the case of a 17-year-old girl with acute renal injury as a side effect of using acyclovir. The patient was admitted for three days due to drug-induced AKI, which was reversed by discontinuing the afflicted medicine (acyclovir), initiating appropriate hydration with intravenous normal saline 0.9%, and refraining from any nephrotoxic medications. Following up a week later, the patient was asymptomatic and had normal kidney function. Therefore, it is critical to use acyclovir correctly to avoid possibly fatal consequences.

ODP130 Zoledronate-Induced Acute Tubular Necrosis With Baseline Normal Renal Function: A Rare Phenomenon

Abstract Introduction Zoledronate is an intravenous bisphosphonate that is commonly used to decrease bone resorption in patients with osteoporosis. The incidence of acute tubular necrosis (ATN) using zoledronate in patients with normal renal function is rare. Herein, we report the occurrence of severe ATN following treatment with a single zoledronate infusion in a patient with osteoporosis and normal renal function. Case Presentation A 51-year-old female with hypertension, well-controlled type 2 diabetes c/b gastroparesis without nephropathy(HbA1c6.8%), status-post hysterectomy, and bilateral oophorectomy, who was recently diagnosed with osteoporosis. Bone densitometry with Hologic revealed T scores of -2.8 at the spine and a T score of - 0.9 at the left hip. Her medications included lisinopril, metformin, and empagliflozin. Due to a history of gastroparesis, zoledronate was chosen as the preferred treatment. Pre-infusion blood work showed: a creatinine of 0.92 (0.5-1.1 mg/dl), 25-hydroxyvitamin-D 37.8 (30-100 NG/ml), calcium 8.9 (8.5-10.5mg/dl) and urine microalbumin 14 (&amp;lt;30 mg/g). Two days after the infusion, the patient developed emesis, diarrhea, oliguria, and fevers. She was evaluated in the emergency room and found to have acute renal failure (creatinine 10 mg/dL). She was given three liters of intravenous fluids with no improvement in urine output. Microscopic evaluation of spun urine revealed non-dysmorphic RBCs and numerous muddy brown granular casts consistent with ATN. Despite treatment with intravenous fluids, her creatinine did not improve and peaked on hospital days 11 to 11.65mg/dl. A 24-hour urine collection revealed proteinuria of 3 grams/24 hours. The patient was then empirically started on methylprednisolone 500mg for suspected glomerulonephritis. A renal biopsy was subsequently performed, which confirmed ATN. The patient's creatinine improved steadily to 5.49mg/dl by discharge. A subsequent creatinine one-month post-discharge was 1.36mg/dL. Discussion Zoledronate is widely used at low doses in the treatment of osteoporosis. ATN due to zoledronate infusion has been described in patients with pre-existing renal dysfunction and those receiving large and frequent doses for malignancy but rarely reported with the lower doses used to treat patients with osteoporosis and normal renal function. Zoledronate is believed to cause ATN by internalization in the renal tubular cells via the process of fluid-phase endocytosis. The intracellular accumulation of zoledronate may act as an epithelial toxin inducing tubular cytotoxicity. Interestingly, our patient had normal renal function without diabetic nephropathy and did not use nephrotoxic medications prior to the infusion. Conclusion We report a case of severe ATN due to a single dose of zoledronate in a patient with osteoporosis and previously normal renal function. This case highlights the need to be aware of the potential nephrotoxicity of zoledronate even in patients with normal renal function at baseline. Presentation: No date and time listed

Case presentations of medication management for patients at risk for drug-associated acute kidney injury identified with a CDS system and a novel biomarker.

Traditional methods used to evaluate changes in kidney function to identify acute kidney injury (AKI) have significant limitations. Damage biomarkers can identify patients at risk for AKI prior to changes in kidney function. While clinical trials have shown that biomarker-guided treatment can improve outcomes, whether these biomarkers can influence providers' choice of treatment strategy for risk prediction, surveillance, or diagnostic evaluation in clinical practice is uncertain. This case series describes 4 patients at an academic medical center whose care was informed by kidney biomarker utilization in conjunction with a clinical decision support system (CDSS). Though each patient's clinical presentation was unique, kidney biomarkers were successfully employed as clinical tools in evaluating the risks and benefits of nephrotoxic medications. This case series demonstrates 4 scenarios in which a kidney injury biomarker used in conjunction with CDSS and consideration of the patients' clinical presentation informed treatment strategies with the intent to prevent AKI.

The Risk and Clinical Implications of Antibiotic-Associated Acute Kidney Injury: A Review of the Clinical Data for Agents with Signals from the Food and Drug Administration's Adverse Event Reporting System (FAERS) Database.

Antibiotic-associated acute kidney injury (AA-AKI) is quite common, especially among hospitalized patients; however, little is known about risk factors or mechanisms of why AA-AKI occurs. In this review, the authors have reviewed all available literature prior to 1 June 2022, with a large number of AKI reports. Information regarding risk factors of AA-AKI, mechanisms behind AA-AKI, and treatment/management principles to decrease AA-AKI risk were collected and reviewed. Patients treated in the inpatient setting are at increased risk of AA-AKI due to common risk factors: hypovolemia, concomitant use of other nephrotoxic medications, and exacerbation of comorbid conditions. Clinicians should attempt to correct risk factors for AA-AKI, choose antibiotic therapies with decreased association of AA-AKI to protect their high-risk patients, and narrow, when clinically possible, the use of antibiotics which have decreased incidence of AKI. To treat AKI, it is still recommended to discontinue all offending nephrotoxic agents and to renally adjust all medications according to package insert recommendations to decrease patient harm.

Prevalence of Contrast-Induced Acute Kidney Injury in Acute Ischemic Stroke Patients Undergoing Contrast-Enhanced CT Angiography at a Tertiary Care Centre

BACKGROUND&#x0D; Multimodal Computed Tomography (CT) imaging with contrast-enhanced CT angiography (CTA) is frequently being used to guide the management of acute ischemic stroke. The administration of contrast media (CM) may lead to nephrotoxicity. However, little has been reported about the safety of intravenous CM exposure in acute stroke patients. This study aims to evaluate whether there is a significant change in renal function following contrast agent administration, determine the proportion of patients developing contrast-induced acute kidney injury(CI-AKI), and analyze the risk factors associated with the same.&#x0D; METHODS&#x0D; We analysed 138 patients with acute ischemic stroke who underwent emergency CTA at our centre, followed up on the renal parameters and prospectively evaluated them for the development of CI-AKI. The patients who developed CI-AKI were analysed for specific risk factors and categorized into risk groups based on a pre-validated risk score. Univariate and multivariate logistic regression was done to identify independent predictors of CI-AKI.&#x0D; RESULTS&#x0D; CI-AKI occurred in 19 patients (13.7%). Significant (p&lt;0.001) changes in renal parameters were observed following contrast administration irrespective of whether it satisfied the criteria for CI-AKI. Most of the patients had a low-risk score for CI-AKI. The predicted risk of CI-AKI based on the Mehran Risk Score (MRS) was similar to that observed in our study population. No patient had to be on haemodialysis. Raised baseline S.creatinine(p-value&lt;0.03), Diabetes with microangiopathy(p-value&lt;0.001), and systemic hypertension(p-value&lt;0.001) were significant predictors for CI-AKI.&#x0D; CONCLUSIONS&#x0D; The development of renal sequelae is low in acute ischemic stroke patients undergoing contrast imaging. Prompt CTA, if indicated, need not be delayed in those with no history of renal impairment or without relevant risk factors. A practical reflection of this study is to be cognizant of the renal risks that an in-patient stroke population is exposed to as Intravascular depletion, infections(urinary tract infections, pneumonia), and nephrotoxic medications.

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.

Renal Impairment Associated With Trimethoprim-Sulfamethoxazole Use in the Pediatric Population.

Limited studies describe acute kidney injury (AKI) in children receiving trimethoprimsulfamethoxazole (SXT). The primary objective of this study was to describe AKI with SXT use in pediatric patients. Secondary objectives included describing the incidence of hyperkalemia and blood dyscrasias with SXT use. In this retrospective, single-center observational study, inpatient electronic medical records were reviewed for patients younger than 18 years of age who received at least 5 days of SXT for treatment of a bacterial infection. Patients were excluded if serum creatinine data prior to and after initiation of SXT were unavailable, they had AKI or were on hemodialysis prior to SXT initiation, or they were admitted to an oncology unit. Of 98 patients who met inclusion criteria, 24 (24.5%) experienced stage I AKI and 16 (16.3%) experienced stage II or III AKI. The mean treatment duration with SXT at time of AKI development was 5.9 days. Coadministration of SXT with other nephrotoxic medications increased the risk of development of AKI (OR, 1.7; 95% CI, 1.2-2.4). Hyperkalemia was noted in 29 patients (29.6%), anemia in 39 patients (39.8%), thrombocytopenia in 30 (30.6%), and neutropenia in 39 (39.8%). Changes in renal function suggestive of AKI occur frequently in pediatric patients receiving at least 5 days of treatment with SXT, particularly when using serum creatinine as a marker of AKI. In contrast, when using urine output rather than serum creatinine, the incidence is much lower and may be more reflective of a true change in renal function. Coadministration of nephrotoxic agents increases the risk of development of AKI. Anemia and hyperkalemia are common in patients receiving SXT and not associated with development of AKI. Further prospective study is warranted to validate these results.

Practical approaches to improve vancomycin-related patient outcomes in pediatrics- an alternative strategy when AUC/MIC is not feasible

BackgroundAnecdotal experience and studies have shown that most pediatric patients fail to reach target therapeutic vancomycin trough levels (VTLs) and required higher total daily doses (TDD). This retrospective study aims to evaluate the frequency of hospitalized children who achieved target VTLs with a vancomycin (VNCO) dosing regimen of 40-60 mg/kg/d q6h and to assess the VNCO-TDD required to attain the target and their effects on clinical outcomes in pediatric patients.MethodsAfter ethical approval, patients of 3 month-12 years were evaluated in this chart review study who received ≥ 3 intravenous-VNCO doses and appropriately drawn blood samples of VTLs between October 2019 to June 2020. Data were retrieved for demographic and clinical characteristics, culture reports, VNCO-regimen, subsequent steady-state VTLs, concomitant nephrotoxic medications, and serum creatinine. Clinical pharmacists made interventions in VNCO therapy and higher VNCO-TDD were used. Safety of higher vs standard daily doses and their clinical impact on duration of therapy, hospital stay, and survival were evaluated.ResultsA total of 89 (39.1%) patients achieved target VTLs (SD-group). The smallest proportion (18.2%) of 2–6 years patients achieved target VTLs and reported the lowest mean value of 10.1 ± 0.2 mg/L which was a significant difference (p < 0.05) from all subgroups. Subtherapeutic VTLs were observed in 139 (60.9%) cases (HD-group), who received higher VNCO-TDD of 72 ± 8.9 mg/kg/d q6h to achieve the targets. Duration of therapy in culture-proven septic patients was significantly (p = 0.025) longer in SD-group [18.4 ± 12.2 days] than HD-group [15.1 ± 8.9 days]. Nephrotoxicity and electrolyte imbalance were comparable in groups. Length of hospital stay was significantly (p = 0.011) longer [median 22 (range 8–55) days] in SD-group compared to HD-group [median 16 (range 8–37) days]. Number of patients survived in HD-group were significantly (p = 0.008) higher than SD-group [129 (92.8%) vs 75 (84.3%)].ConclusionInitial Vancomycin doses of 72 ± 8.9 mg/kg/day q6h are required to achieve therapeutic target in 3 months to 12 years patients. High doses are not associated with higher nephrotoxicity than reported with low doses. In addition, efficient pharmacist intervention for the use of higher VNCO-TDD may improve clinical outcomes in terms of duration of therapy, hospital stay, and survival.