Protective Effects of Montelukast on Vancomycin-Associated Acute Kidney Injury in Children: A Randomized Clinical Trial

BackgroundPotentially nephrotoxic drugs play an important role in acute kidney injury (AKI) in children. In the previous pharmacovigilance study, we found a statistical correlation between diazepam and AKI in children, but the causality needs to be further verified.MethodsAn observational cohort study was conducted to investigate the association between diazepam exposure and the risk of AKI in hospitalized children. The exposed group received diazepam while the control group did not. The outcome was AKI in accordance with the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Logistic regression was used to explore the association between diazepam exposure and the risk of AKI in children after adjusting for covariates.ResultsA total of 3018 hospitalized children were included, 148 in the diazepam group and 2870 in the control group. After adjusting for covariates, diazepam exposure was associated with an increased risk of AKI in children (OR = 1.85, 95%CI: 1.11–3.09, P = 0.019). Multivariate logistic regression showed that age (P < 0.001), low baseline serum creatinine (P < 0.001), chronic kidney disease (P = 0.039), diuretics (P = 0.009), Non-steroidal anti-inflammatory drugs (NSAIDs, P = 0.046), proton pump inhibitors (P = 0.007) and vasoactive drugs (P = 0.007) were risk factors for diazepam-associated AKI in children.ConclusionsThe use of diazepam in children is associated with an increased risk of AKI. The risk factors for diazepam-associated AKI in children included age, low baseline serum creatinine, chronic kidney disease, diuretics, NSAIDs, proton pump inhibitors, and vasoactive drugs.Trial registrationChiCTR2400085281 2024-06-04 (retrospectively registered).

To investigate the incidence and risk factors for acute kidney injury (AKI) in children with primary nephrotic syndrome (PNS), as well as the role of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in the early identification of AKI in these children. A prospective collection of clinical data from children hospitalized with PNS at the Children's Hospital of the Capital Institute of Pediatrics from January 2021 to October 2022 was conducted. The children were divided into two groups based on the presence of AKI: the AKI group (47 cases) and the non-AKI group (169 cases). The risk factors for AKI in children with PNS were identified by multivariate logistic regression analysis. Urinary KIM-1 and NGAL levels were compared between the AKI and non-AKI groups, as well as among the different stages of AKI. The incidence of AKI in children with PNS was 21.8%. Multivariate logistic regression analysis revealed that steroid-resistant nephrotic syndrome, gastrointestinal infections, and heavy proteinuria were independent risk factors for AKI in these children with PNS (P<0.05). Urinary KIM-1 and NGAL levels were higher in the AKI group compared to the non-AKI group (P<0.05), and the urinary NGAL and KIM-1 levels in the AKI stage 2 and stage 3 subgroups were higher than those in the AKI stage 1 subgroup (P<0.017). KIM-1 and NGAL can serve as biomarkers for the early diagnosis of AKI in children with PNS. Identifying high-risk populations for AKI in children with PNS and strengthening the monitoring of related risk factors is of significant importance.

To investigate the incidence rate of acute kidney injury (AKI) in children with type 1 diabetes and diabetic ketoacidosis (DKA) and the risk factors for AKI in children with DKA. A retrospective analysis was performed on 45 children with type 1 diabetes and DKA who attended Children's Hospital of Nanjing Medical University from 2018 to 2020. According to the presence or absence of AKI on admission, they were divided into two groups: non-AKI (n=37) and AKI (n=8). Socio-demographic data and physical examination data on admission were collected, including height, weight, blood pressure, and heart rate. Chemiluminescence particle immunoassay was used to determine the levels of serum creatinine and blood urea nitrogen on admission and at discharge. The multivariate logistic regression model was used to assess the risk factors for AKI in children with type 1 diabetes and DKA. The 45 children had a median age of 9.2 years at diagnosis. Among the 8 children (18%) with AKI on admission, 6 had stage 1 AKI and 2 had stage 3 AKI. An increase in corrected serum sodium level was an independent risk factor for AKI in children with type 1 diabetes and DKA (P<0.05), and a relatively high insulin level on admission was an independent protective factor against AKI (P<0.05). There is a high incidence rate of AKI in children with type 1 diabetes and DKA. It is important to correct DKA actively, control blood glucose in time, and perform renal function tests and follow-up regularly in such children.

Objective: To comprehensively evaluate the effectiveness of preventive measures for acute kidney injury (AKI) in children and identify the effective strategies. Methods: Databases were systematically searched including CNKI, Wanfang, VIP, China Biology Medicine National Knowledge Infrastructure, PubMed, Embase, Cochrane Library databases, and the reference lists of relevant papers for randomized controlled trials on preventing pediatric AKI up to December 2023. Literature screening was conducted based on the inclusion and exclusion criteria, followed by data extraction and quality assessment of included studies. Traditional and network meta-analyses were performed, along with trial sequential analysis (TSA). Results: A total of 21 studies involving 3 483 children were included. Traditional and network meta-analysis showed that dexmedetomidine was effective in preventing AKI in children undergoing cardiac surgery or cardiac angiography (OR=0.26, 0.27; 95%CI 0.11-0.64, 0.13-0.58). Remote ischemic preconditioning (RIPC) was effective in preventing AKI in children after cardiac surgery (OR=0.43, 0.44; 95%CI 0.24-0.79, 0.23-0.83). Traditional and network meta-analysis specific to children with sepsis or septic shock showed that balanced solution was effective in preventing pediatric AKI (OR=0.58, 0.52; 95%CI 0.42-0.79, 0.37-0.73). TSA indicated that the total sample sizes of dexmedetomidine (348 cases) and RIPC (666 cases) both reached the required information size (320 and 534 cases); additionally, the Z-curve for balanced solution (cumulative Z=3.38) crossed the TSA monitoring boundary (Z=3.29). Conclusion: Dexmedetomidine reduces the risk of AKI in children undergoing cardiac surgery or cardiac angiography, RIPC decreases the risk of AKI in children after cardiac surgery, and balanced solution lowers the risk of AKI in children with sepsis or septic shock.

Our goal was to identify risk factors for acute kidney injury in children surviving cardiac arrest. Retrospective analysis of a public access dataset. Fifteen children's hospitals associated with the Pediatric Emergency Care Applied Research Network. Two hundred ninety-six subjects between 1 day and 18 years old who experienced in-hospital or out-of-hospital cardiac arrest between July 1, 2003, and December 31, 2004. None. Our primary outcome was development of acute kidney injury as defined by the Acute Kidney Injury Network criteria. An ordinal probit model was developed. We found six critical explanatory variables, including total number of epinephrine doses, postcardiac arrest blood pressure, arrest location, presence of a chronic lung condition, pH, and presence of an abnormal baseline creatinine. Total number of epinephrine doses received as well as rate of epinephrine dosing impacted acute kidney injury risk and severity of acute kidney injury. This study is the first to identify risk factors for acute kidney injury in children after cardiac arrest. Our findings regarding the impact of epinephrine dosing are of particular interest and suggest potential for epinephrine toxicity with regard to acute kidney injury. The ability to identify and potentially modify risk factors for acute kidney injury after cardiac arrest may lead to improved morbidity and mortality in this population.

To investigate the risk factors and prognosis of acute kidney injury (AKI) in children with sepsis in pediatric intensive care unit (PICU). A retrospective analysis of clinical data of PICU sepsis children in Anhui Children's Hospital from May 2015 to May 2018 was performed. The children were divided into AKI group and non-AKI group according to whether AKI occurred within 48 hours of PICU [referring to the diagnostic criteria for Kidney Disease: Improving Global Outcomes (KDIGO)]. The general data, physiological data and clinical outcomes of the two groups were compared; Logistic regression analysis was used to analyze the risk factors of AKI in children with sepsis and the prognostic factors. AKI occurred in 55 of 127 children with sepsis, the incidence of AKI was 43.3%, and the overall mortality was 28.3% (36/127), with 41.8% (23/55) in AKI group and 18.1% (13/72) in non-AKI group. (1) Compared with non-AKI group, oxygenation index, albumin, the pediatric critical illness case score (PCIS) and urine volume in AKI group were significantly decreased, while cystatin C, procalcitonin (PCT), prothrombin time (PT), activated partial thromboplastin time (APTT), pediatric multiple organ dysfunction score (P-MODS), the proportions of mechanical ventilation, vasoactive drug use, shock, septic shock and mortality were significantly increased, while there was no difference in age, gender, mean arterial pressure (MAP), white blood cell count (WBC) and C-reactive protein (CRP) between the two groups. Multivariate Logistic regression analysis showed that low serum albumin [odds ratio (OR) = 0.627, 95% confidence interval (95%CI) = 0.495-0.794, P = 0.000] and homocystatin C (OR = 2.641, 95%CI = 1.157-6.032, P = 0.021) were risk factors for AKI in children with sepsis. (2) Compared with the survival group of children with sepsis AKI, the proportion of mechanical ventilation, septic shock, vasoactive drug use, positive balance ratio of liquid for 72 hours, 6-hour lactate clearance rate < 10%, and AKI 3-stage patients in the death group of children with sepsis AKI were significantly increased. Multivariate Logistic regression analysis showed that 72-hour positive liquid balance (OR = 8.542, 95%CI = 1.956-37.307, P = 0.004) and 6-hour lactate clearance rate < 10% (OR = 5.980, 95%CI = 1.393-25.676, P = 0.016) were risk factors for the death of children with sepsis AKI. Serum albumin and cystatin C should be closely monitored in children with sepsis. Early detection and intervention of positive fluid balance and low lactate clearance rate can reduce the mortality of AKI in children with sepsis.

The incidence of acute kidney injury (AKI) in children is increasing globally and is associated with increased mortality and long-term renal consequence.The definition of pediatric AKI was standardized for a more accurate assessment of the epidemiology of pediatric AKI. The definition of AKI is based on elevation in serum creatinine levels or decrease inurine output; accordingly, epidemiological studies have ensued. Recent advances in leveraging electronic medical health record systems and newbiomarkers appear to detect AKI earlier and predict prognosis more accurately than traditional markers have allowed for real-time risk stratification and prevention of pediatric AKI in the hospital setting. For high risk or early stage AKI patients, avoidance of nephrotoxins, optimization of blood pressure and volume status, sufficient nutritional support are necessary and have been demonstrated tobe effective in preventing the occurrence of AKI and improving prognosis. Lastly, renal replacement therapy is needed when conservative care fails. Further therapeutic innovation willdepend on improving the understanding of the basic mechanisms underlying AKI in children. CBMJ 2018 January: Vol. 07 No. 01 P: 48-53

No large cohort study has yet determined the incidence of acute kidney injury (AKI) in children with heart failure treated with renin-angiotensin system (RAS) inhibitors. We thus retrospectively analyzed the incidence and risk factors for severe AKI (stages 2-3 according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines) at our institutions from 2008 to 2011. Among 312 children (162 boys; median age, 7.3 months), 59 cases of AKI occurred in 45 children. The incidence of AKI was 14.3 cases per 100 person-years overall (follow-up 413.6 person-years), or 27.3, 16.8, and 4.5 cases per 100 person-years in children aged <1, 1-3, and ≥4 years, respectively. Among them, 23 (39.0 %) children had metabolic acidosis and 14 (23.7 %) had hyperkalemia. Younger age, myocardial disease, cyanotic congenital heart disease, use of spironolactone, and cardiac surgery were independent risk factors for AKI. Furthermore, 37.3 % of children suffered dehydration during AKI. AKI incidence is relatively high in children, particularly younger children, with heart failure treated using RAS inhibitors. Careful monitoring of renal function and serum electrolytes is essential. Proper management of fluid balance after infection and cardiac surgery may reduce the risk of AKI. Temporary discontinuation in RAS inhibitors should be considered during dehydration or surgery. • Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the two main classes of renin-angiotensin system (RAS) inhibitors used to treat hypertension, heart failure, and chronic kidney disease. Acute kidney injury (AKI) and hyperkalemia are potentially life-threatening complications associated with the use of ACEIs and ARBs. Some reports have suggested that dehydration and cardiac surgery are risk factors for AKI in children. However, no large-scale cohort studies have determined the incidence of AKI, its risk factors, and its outcomes in children with heart failure treated with ACEIs and/or ARBs. What is new: • In this retrospective cohort study, we determined the incidence, severity, and risk factors for severe AKI in children with heart failure treated with ACEIs and/or ARBs. The incidence of AKI in these children was relatively high (14.3 episodes per 100 person-years). In addition, younger age, myocardial disease, cyanotic congenital heart disease, concomitant use of spironolactone, and cardiac surgery were risk factors for AKI. Furthermore, 37.3 % of children had dehydration during AKI episodes. • Our results suggested that appropriate fluid balance after infection and cardiac surgery might reduce the risk of AKI and its complications. Temporary discontinuation or reductions in the levels of ACEIs and/or ARBs during dehydration or before surgery may also be warranted in these patients.

To analyze the epidemiology of acute kidney injury (AKI) in children with lymphoma and to assess the incidence, risk profile of AKI, and effects on renal function in children with lymphoma during their first 30 days of hospitalization. This was a retrospective screen of electronic hospital and laboratory databases to select hospitalized children who were first diagnosed and treated for lymphoma at Beijing Children's Hospital between 2020 and 2021. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. We analyzed the incidence and risk factors for AKI in children with lymphoma during their first 30 days of hospitalization. We also analyzed mortality rate and the incidence of kidney recovery over a 1-year follow-up period. Of the 295 children with lymphoma (which were all non-Hodgkin lymphoma), 42 (16.5%) experienced AKI events during the first their 30 days of hospitalization. The proportion of patients with lymphoma clinical stage 4 was higher in the AKI group than in the non-AKI group (66.7 vs. 43.7%, p<0.05). Tumor lysis syndrome (TLS), lung infection, and lymphoma clinical stage were identified as independent risk factors for AKI in children with lymphoma. Severe AKI was associated with TLS, sepsis, and a higher need for intensive care. Over 1-year of follow-up, none of the survivors developed impaired renal function or proteinuria. However, the mortality of children in the AKI group was significantly higher than that in the non-AKI group (p<0.05). TLS, lung infection, and lymphoma clinical stage were identified as independent risk factors for AKI in children with lymphoma during the first 30 days of hospitalization. Clinicians should increase their awareness of AKI in hospitalized patients with lymphoma.

Introduction:There is considerable controversy on the accuracy of Kidney Injury Molecule-1 (KIM-1) in prediction of acute kidney injury (AKI) in children. Therefore, the present study intends to provide a systematic review and meta-analysis of the value of this biomarker in predicting AKI in children.Methods:An extensive search was performed on the Medline, Embase, Scopus and Web of Science databases by the end of 2019. Cohort and case-control studies on children were included. Urinary KIM-1 levels were compared between AKI and non-AKI groups. Findings were reported as an overall standardized mean difference (SMD) with a 95% confidence interval (CI). Also, the overall area under the receiver operating characteristic (ROC) curve (AUC) of KIM-1 in predicting AKI in children was calculated.Results:Data from 13 articles were included. Urinary KIM-1 levels in children with stage 1 AKI were higher than the non-AKI group only when assessed within the first 12 hours after admission (SMD = 0.95; 95% CI: 0.07 to 1.84; p = 0.034). However, urinary KIM-1 levels in children with stage 2-3 AKI were significantly higher than non-AKI children (p <0.01) at all times. The AUC of urinary KIM-1 in predicting AKI in children was 0.69 (95% CI: 0.62 to 0.77).Conclusion:Based on the available evidence, KIM-1 seems to have moderate value in predicting AKI in children. Since previous meta-analyses have provided other urinary and serum biomarkers that have better discriminatory accuracy than KIM-1, so it had better not to use KIM-1 in predicting AKI in children.

Right ventricular dysfunction (RVD) is a complication following congenital cardiac surgery in children and can lead to systemic venous congestion, low cardiac output, and organ dysfunction. Venous congestion can be transmitted backwards and adversely affect encapsulated organs such as the kidneys. To investigate the association between systemic venous congestion, as estimated by Venous Excess Ultrasound (VExUS), and the occurrence of acute kidney injury (AKI) in children with RVD following congenital heart surgery. Secondary objectives included comparing changes in VExUS scores after initiating treatment for RVD and venous congestion. This was a prospective observational study in children with RVD. The VExUS study was performed on day 1, day 2, and day 3 and categorized as VExUS-1, VExUS-2, and VExUS-3. Among 43 patients with RVD and dilated inferior vena cava, 19/43 (44%), 10/43 (23%), and 12/43 (28%) were VExUS-2 and VExUS-3, respectively. There was an association between severe RVD and elevated pulmonary artery systolic pressures and a VExUS score >2. A significant association was observed between central venous pressure (CVP) measurements and VExUS. Among 31 patients with a high VExUS score >2, 18 (58%) had AKI. Additionally, improvement in CVP and fluid balance was associated with improving VExUS scores following targeted treatment for RVD. VExUS serves as a valuable bedside tool for diagnosing and grading venous congestion through ultrasound Doppler. An elevated VExUS score was associated with the occurrence of AKI, and among the components of VExUS, portal vein pulsatility may be useful as a predictor of AKI. Natraj R, Bhaskaran AK, Rola P, Haycock K, Siuba MTT, Ranjit S. Venous Congestion Assessed by Venous Excess Ultrasound (VExUS) and Acute Kidney Injury in Children with Right Ventricular Dysfunction. Indian J Crit Care Med 2024;28(5):447-452.

ObjectiveThis study aimed to investigate the clinical features and risk factors of acute kidney injury (AKI) in children with acute paraquat intoxication.MethodsA retrospective study of 110 hospitalized children with acute paraquat intoxication in West China Second University Hospital, Sichuan University was conducted from January 2010 to May 2017. The Kaplan–Meier method was used to compare the survival rates of children with different AKI stages. Multivariate logistic regression was applied to analyse the risk factors for paraquat-induced AKI.ResultsAKI occurred in 42 of 110 (38.2%) children. We observed AKI stage 1 in two (4.8%) children, AKI stage 2 in 11 (26.2%), and AKI stage 3 in 29 (69.0%). The survival rate of children in AKI stage 3 (34.5%) was significantly lower than that in children in AKI stage 2 (63.6%) and AKI stage 1 (100%). Multivariate analysis showed that oral ulcers and elevated blood glucose levels were significant independent risk factors for paraquat-induced AKI in children (odds ratio = 4.223 and 5.545, respectively).ConclusionsThe incidence and mortality rates of paraquat-induced AKI in children are high. Oral ulcers and elevated blood glucose levels are independent risk factors affecting the occurrence of paraquat-induced AKI in children.

World Kidney Day 2013: Acute Kidney Injury—Global Health Alert

Unexplained acute kidney injury (AKI) in children owing to diethylene glycol (DEG) contamination during drug production has gained attention in recent years. This qualitative study investigated the effects of DEG exposure on the incidence of unknown AKI in children. A systematic review following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines was proposed to search for studies using predefined search terms in the PubMed, EBSCO, and Web of Science data-bases without publication date restrictions. The inclusion criteria are observational study, case study, case report, and case series design; and having provided accurate data for DEG poisoning and AKI diagnosis in children. All authors performed the study screening, data extraction, and data synthesis processes. Consensus was reached by mutual agreement. The data synthesis was conducted according to the DEG and unexplained AKI in children by examining the statistical data using Microsoft Excel 2017 and storing the data using the cloud service of Universitas Islam Indonesia. Of the 115 included studies, 21 met the inclusion criteria, including 2 case-control studies, 1 cross-sectional study, 4 case studies, and 14 case reports. DEG-contaminated paracetamol caused unexplained AKI in children. Other drugs including cough expectorants, antihistamines, and sedatives were administered. Chemicals other than DEG, such as propylene glycol and ethylene glycol, also induce AKI owing to overprescription and unintentional exposure. A recent epidemic of unexplained AKI showed contaminated paracetamol as the poisoning agent regardless of formula.

Acute Kidney Injury (AKI) in Indonesian children under five increased sharply in 2022. To determine maternal knowledge about AKI in children. A descriptive analytical design was conducted with 400 mothers selected through purposive sampling using an online questionnaire; data were analyzed using univariate and bivariate methods. Most respondents had one toddler (82.5%), were vocational-level graduates (72.5%), and housewives (75.7%). A total of 97.7% expressed anxiety about AKI, while 70.8% had low knowledge of its causes, symptoms, complications, and prevention. Knowledge was significantly associated with age, education, employment status, and anxiety (p=0.000). Maternal knowledge about AKI in children remains inadequate. Nurses need to provide more intensive and targeted education to increase mothers' awareness and ability to handle AKI in children