Acute kidney injury (AKI) has been reported during diabetic ketoacidosis (DKA). Evidence regarding tubulopathy is less established, with its pathophysiology, risk determinants, and short-term outcome to be unraveled. Hence, this study aimed to assess renal tubular functions during DKA, its short-term outcome, and its relation with urinary Netrin-1, DKA severity, and renal perfusion indices. Forty children and adolescents (20 with moderate and 20 with severe DKA) were assessed for urine output (UOP), blood pressure, blood glucose, HbA1c, and urinary Netrin-1, with calculation of serum osmolality and estimated glomerular filtration rate (eGFR). Renal pulsatility and resistivity indices were assessed by renal duplex. Reevaluation was done on days 3 and 14. Sixteen children and adolescents had tubular proteinuria during DKA (40%). Their mean urine output (UOP) during DKA was 14.03 cc/kg/h, and their mean urinary Netrin-1 was 836.9 ng/ml. A significant improvement was observed in the UOP, protein/creatinine ratio, urinary netrin, and serum osmolality after the resolution of DKA accompanied by a significant decrease in renal resistivity and pulsatility indices (p < 0.05). A significant positive correlation was found between tubular proteinuria during DKA and urinary Netrin-1, renal pulsatility, and resistivity indices (p < 0.05). Multivariate regression analysis revealed that serum PH and urinary Netrin-1 were the most significant independent variables associated with tubular proteinuria among children and adolescents during DKA.

Transient renal tubulopathy occurs during DKA manifested by tubular proteinuria, polyuria, and hypokalemia; that is correlated with DKA severity, renal perfusion indices, and urinary Netrin-1 and reversible by day 14 post-DKA. Netrin-1 could serve as a potential therapeutic target for DKA-associated tubulopathy.

• Diabetic ketoacidosis (DKA) is a severe acute complication of diabetes mellitus, with negative effect on multiple body organs. • Studies increasingly suggest acute kidney injury during DKA, however, data about renal tubular injury during DKA, it's pathophysiology, risk determinants and short term outcomes are still unclear.

• Transient renal tubulopathy was reported in 40 % the studied children and adolescents during DKA manifested by proteinuria, polyurea, and hypokalemia. • This tubulopathy that was correlated with DKA severity, renal perfusion indices and urinary Netrin-1 and totally reversible by day 14 post DKA.

There are two criteria to diagnose and stage acute kidney injury (AKI) in children: pediatric-Risk, Injury, Failure, Loss (p-RIFLE) and Kidney Disease Improving Global Outcomes (KDIGO). This study aims to find out the extent of agreement in diagnosis (by p-RIFLE and KDIGO) and risk factors of AKI in pediatric diabetic ketoacidosis (DKA).

A retrospective cohort study involving children aged ≤15 years with DKA was conducted between January 2014 and December 2022. Those with inborn errors of metabolism, septic shock, and urinary tract disease were excluded. The primary outcome was the extent of agreement in diagnosis of AKI by p-RIFLE and KDIGO. The secondary outcomes were staging agreement, risk factors, complications (hypoglycemia, hypokalemia, and cerebral edema), time to resolution of DKA, and hospital and pediatric intensive care units (PICU) stay.

Data from 161 patients were collected. Mean (SD) age was 8.6 (3.7) years. Good agreement between p-RIFLE and KDIGO criteria for diagnosis of AKI was noted at admission (Kappa = 0.71, p ≤ 0.001), at 24 hours (Kappa = 0.73, p ≤ 0.001) and discharge (Kappa = 0.60, p ≤ 0.001), and for the staging of AKI at admission (Kappa = 0.81, p ≤ 0.001) at 24 hours (Kappa = 0.75, p ≤ 0.001) and discharge (Kappa = 0.48, p ≤ 0.001). On multivariate analysis, age (≤5 years: aOR = 3.03, 95% CI 1.04-8.79) is an independent risk factor for AKI at discharge by KDIGO. Cerebral edema (n = 6, 3.7%), hypoglycemia (n = 66, 41%), and hypokalemia (n = 59, 36.6%) were noted. Resolution and stay in PICU and hospitals were longer for patients with AKI.

p-RIFLE and KDIGO criteria showed good agreement in diagnosis and staging of AKI in pediatric DKA.

Preterm birth remains the leading cause of mortality among neonates. Despite improvements in neonatal intensive care over the years, current treatments for lung and kidney failure are highly invasive, associated with lifelong disability, and limit family integration. Artificial womb and artificial placenta technologies offer a promising alternative by providing more tailored and less invasive neonatal care. Although these technologies share some similarities, artificial womb and artificial placenta technologies differ significantly in terms of treatment initiation, treatment environment, and the potential to support family-centered care. Moreover, even though acute kidney injury is common in neonatal extracorporeal membrane oxygenation (ECMO) patients, current artificial placenta and artificial womb devices lack renal support functionality. Most artificial womb and artificial placenta studies focus on the technical feasibility of these technologies based on in-vivo animal tests. However, translation toward envisioned use of these devices in preterm neonates remains mostly underexposed. A comprehensive stakeholder analysis, including parents and caregivers, is critical to the development of socially acceptable artificial placenta and artificial womb systems. This state-of-the-art review provides an overview of conventional neonatal lung and kidney treatments, delineates the differences between artificial womb and placenta technologies, and addresses the technological and ethical challenges in advancing these technologies toward potential clinical implementation.

Myocardial protection against ischaemia-reperfusion injury is a key determinant of heart function and outcome following cardiac surgery in children. However, myocardial injury still occurs routinely following aortic cross-clamping, as demonstrated by the ubiquitous rise in circulating troponin. del Nido cardioplegia was designed to protect the immature myocardium and is widely used in the USA but has not previously been available in the UK, where St. Thomas' blood cardioplegia is most common. The del Nido versus St. Thomas' blood cardioplegia in the young (DESTINY) trial will evaluate whether one solution is better than the other at improving myocardial protection by reducing myocardial injury, shortening ischaemic time and improving clinical outcomes.

The DESTINY trial is a multicentre, patient-blinded and assessor-blinded, parallel-group, individually randomised controlled trial recruiting up to 220 children undergoing surgery for congenital heart disease. Participants will be randomised in a 1:1 ratio to either del Nido cardioplegia or St. Thomas' blood cardioplegia, with follow-up until 30 days following surgery. The primary outcome is area under the time-concentration curve for plasma high-sensitivity troponin I in the first 24 hours after aortic cross-clamp release. Secondary outcome measures include the incidence of low cardiac output syndrome and Vasoactive-Inotropic Score in the first 48 hours, total aortic cross-clamp time, duration of mechanical ventilation and lengths of stay in the paediatric intensive care unit and the hospital.

The trial was approved by the West Midlands-Coventry and Warwickshire National Health Service Research Ethics Committee (21/WM/0149) on 30 June 2021. Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Parents will be informed of the results through a newsletter in conjunction with a national charity.

ISRCTN13638147; Pre-results.

Current indicators for monitoring intraoperative organ function remain predominantly indirect, delayed and non-specific, particularly in paediatric populations undergoing congenital heart surgery, where multifactorial influences further complicate functional assessments. Emerging evidence suggests that the use of near-infrared spectroscopy (NIRS) technology to continuously monitor the regional oxygen saturation (rSO₂) of intraoperative organs can predict the postoperative organ functional status. This study aims to investigate the associations between intraoperative cerebral/renal rSO₂ fluctuations monitored by NIRS and postoperative neurological injury or acute kidney injury (AKI) in paediatric congenital heart disease (CHD) surgery.

In this prospective observational cohort study, patients ≤18 years, scheduled for CHD surgery under cardiopulmonary bypass (CPB), will be enrolled after obtaining written informed consent. Exclusion criteria include pre-existing neuropsychiatric disorders, chronic kidney disease or other related disorders. Dual-channel NIRS probes will be applied to simultaneously monitor cerebral and renal rSO₂ from anaesthesia induction until the patient is transferred to the cardiac care unit. Serum S100 calcium-binding protein B (S100B) levels will be measured before CPB, at the end of the surgery and on postoperative day 1 to quantify cerebral injury. AKI will be diagnosed using the paediatric risk, injury, failure, loss, end-stage renal disease (pRIFLE) criteria based on dynamic creatinine changes. Health-related quality of life will be assessed through the paediatric quality of life (PedsQL) inventory at preoperative baseline and postoperative day 30.

This study has been approved by the Institutional Review Board of Beijing Children's Hospital (approval number: [2024]-Y-093-D). Prior to enrolment, written informed consent will be obtained from the parents or legal guardians of all participating minors. The findings of this research will be disseminated through peer-reviewed publications and presentations at relevant conferences and shared with participating communities via lay summaries and social media platforms.

The study was registered with the Chinese Clinical Trial Registry on 18 April 2024 (ChiCTR2400083225).

This was a prospective, longitudinal study, of 40 children who had open heart surgery, on account of congenital heart diseases, at our study center, between April 2020 and June 2022. Plasma samples were assayed for cystatin-C using the enzyme-linked immunosorbent assay method, while quantification of creatinine was done using a Roche automated analyzer (Cobas C311).

Mean plasma concentrations of cystatin-C at 0, 4, 8, 12, 24 and 48 hours were 0.49±0.11 ng/dL, 0.75 ± 0.19 ng/dL, 0.96 ± 0.23 ng/dL, 0.79 ± 0.20 ng/dL, 0.66 ± 0.15 ng/dL, and 0.60 ± 0.14 ng/dL, respectively, versus 48.98 ± 11.6 μmol/L, 59.65 ± 13.06 μmol/L, 63.00 ± 16.53 μmol/L, 64.90 ± 17.65 μmol/L, 68.50 ± 19.99 μmol/L, and 70.78 ± 21.86 μmol/L, respectively, of creatinine. Plasma cystatin-C peaked earlier at 8 hours compared to creatinine, which peaked at 48 hours. The ROC curve showed that cystatin-C had an AUC of 0.983.

This study showed that cystatin-C has a better sensitivity and specificity than creatinine in predicting CSA-AKI in children who had open heart surgery for congenital heart diseases.

Although goal-directed perfusion (GDP) during cardiopulmonary bypass (CPB) has been discussed extensively in adult studies, no pediatric indexed oxygen delivery (Do2i) thresholds are universally accepted, and no pediatric randomized controlled trial has been reported. This study aimed to determine whether the GDP initiative (maintaining Do2i ≥360 mL/min/m2 during CPB) could reduce the incidence of acute kidney injury (AKI) after pediatric cardiac operation and improve clinical outcomes.

This single-center randomized controlled trial enrolled 312 pediatric patients, who were randomized to receive either the GDP strategy or a conventional perfusion strategy during CPB. The primary outcome was the rate of postoperative AKI. Secondary outcomes included major postoperative complications, all-cause mortality within 30 days, and short-term clinical outcomes after operation.

AKI occurred in 43 patients (28.1%) in the GDP group and in 65 patients (42.2%) in the control group (relative risk, 0.67; 95% CI, 0.49-0.91; P = .010). In the subgroup analysis, the GDP group had a lower AKI rate compared with the control group among patients aged less than 1 year, with a nadir temperature greater than 32 °C and a nadir hemoglobin value less than 8 g/L during CPB, with preoperative cyanosis, and with CPB duration from 60 to 120 minutes.

The GDP strategy aimed at maintaining Do2i ≥360 mL/min/m2 during CPB is effective in reducing the risk of AKI after pediatric cardiac operation.

The association between the hemoglobin-to-red cell distribution width ratio (HRR) and mortality in critically ill patients with heart failure (HF) and acute kidney injury (AKI) remains uncertain. This research focuses on exploring the association between HRR and both short-term and long-term all-cause mortality in these patients.

Participants were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and categorized into tertiles based on HRR values. The primary endpoint was 28-days ICU all-cause mortality. Secondary endpoints included 28-days hospital and 90-days hospital all-cause mortality. Cox proportional hazards models and restricted cubic splines were used to analyze the association between HRR and mortality in patients with HF and AKI. Kaplan-Meier survival analysis estimated endpoint differences across tertiles.

A total of 7561 patients were included, with 55.5% being male (n=4199). Cox proportional hazards analysis showed a significant link between HRR and both short-term and long-term mortality in critically ill patients with HF and AKI. This association remained significant after adjusting for confounders. The restricted cubic splines model demonstrated a linear relationship between a higher HRR index and a reduced mortality risk. Kaplan-Meier survival analysis revealed significant differences in short-term and long-term mortality among the tertile groups.

The study results show a strong association between lower HRR and increased short-term and long-term mortality in critically ill patients with heart failure and AKI. HRR proves to be a valuable and cost-effective marker for identifying high-risk patients.

Acute kidney injury (AKI) is a common postoperative complication of paediatric congenital heart disease (CHD) surgery, associated with increased morbidity and mortality. Current diagnostic approaches are unreliable in the early postoperative period, delaying diagnosis and treatment. This study investigates the efficacy of inflammatory and renal biomarkers in the early detection of postoperative AKI in paediatric CHD surgery patients. Biomarkers were assessed in urine and serum samples collected pre- and 24 h postoperatively from paediatric patients (median age 27 weeks) undergoing corrective CHD surgery (n = 76). Univariate and subsequent multivariate regression analysis with least absolute shrinkage and selected operator (LASSO) regularisation was performed to identify key predictors stratified by AKI diagnosis at 48 h. Significant biomarkers were included in a compound regression model which was evaluated through receiver operator curve analysis. Internal validation of the models was carried out through bootstrapping. Postoperative urine concentrations of interleukin-18 were significantly higher in those with postoperative AKI (p = 0.015), whereas uromodulin concentrations were lower (p = 0.010). Uromodulin, interleukin-18, and serum Fatty Acid Binding Protein 3 were associated with AKI (p = 0.011, 0.040, 0.042 respectively), with uromodulin and interleukin-18 performing strongly in a compound model withstanding LASSO regularisation, demonstrating an area under the curve of 0.899, sensitivity of 0.741, and specificity of 0.913. Urine uromodulin and interleukin-18 can be used to accurately predict postoperative AKI when measured at 24 h after surgery. Prompt recognition of postoperative AKI would facilitate early intervention, potentially mitigating the most severe consequences of renal injury.

Acute kidney injury (AKI) is a significant health concern in hospitalized children and is associated with increased mortality. However, the true burden of AKI-associated mortality in pediatric populations remains unclear.

To determine the pooled incidence of mortality independently associated with AKI in hospitalized children globally.

Medline and Embase were searched for studies published by March 2024.

The inclusion criteria encompassed observational studies involving hospitalized pediatric patients (< 18 years old) with AKI. Only studies that identified AKI as an independent risk factor for increased mortality in multivariate analysis were considered.

Studies with at least 100 AKI patients were included in the meta-analysis. Two authors extracted data on the study and patients' characteristics and mortality across AKI stages and assessed the risk of bias. We used a random-effects meta-analysis to generate pooled estimates of mortality.

Analysis of 60 studies including 133,876 children with AKI revealed a pooled in-hospital mortality rate of 18.27% (95% CI: 14.89, 21.65). Mortality increased with AKI severity; 8.19% in stage 1, 13.44% in stage 2, and 27.78% in stage 3. Subgroup analyses showed no significant differences across geographical regions, income levels, or AKI definition criteria. The pooled post-discharge mortality rate was 6.84% (95% CI: 5.86, 7.82) in a 1-9-year follow-up period.

This meta-analysis demonstrates a substantial global burden of AKI-associated mortality in hospitalized children, with higher mortality rates in more severe AKI stages. These findings highlight the critical need for early detection and intervention strategies in pediatric AKI management.

Not applicable.

Postoperative acute kidney injury (AKI) is a common postoperative complication in cardiac surgery, with varying reported incidences and prognostic factors. Renal hypoperfusion is believed to be a key factor contributing to postoperative AKI. Near-infrared spectroscopy (NIRS) monitoring, which assesses regional tissue saturation (RSO2), has been suggested as a tool to predict postoperative AKI. The aim of this systematic review was to examine the prognostic value of perioperative NIRS monitoring in predicting postoperative AKI in pediatric patients.

After a systematic search in PubMed, EMBASE, and Cochrane library, twenty studies (1517 patients) were included. The inter-rater agreement on study quality was strong, yet a high risk of bias was identified.

The heterogeneity of the results-in part attributable to several potential confounding factors regarding study population, monitoring technique and the definition of AKI-together with the lack of a clear and consistent association between RSO2 values and AKI, currently preclude recommending NIRS monitoring as a reliable and valid clinical tool to "predict" AKI in the individual patient.

Patients with primary ciliary dyskinesia (PCD) are commonly treated for pulmonary exacerbations with intravenous tobramycin, but data on tobramycin pharmacokinetics in PCD is lacking. The objective of this study was to compare tobramycin pharmacokinetics in pediatric patients with PCD to those with cystic fibrosis (CF).

This retrospective study included pediatric patients hospitalized for a pulmonary exacerbation between January 2018 and June 2023. Included patients were treated with systemic tobramycin and had two concentrations usable to calculate patient-specific pharmacokinetics. Each patient with PCD was matched 1:2 to patients with CF based on age. The primary outcome was tobramycin elimination rate constant.

Seven patients with PCD were matched to 14 patients with CF. Baseline characteristics were similar between groups. The final tobramycin dose was not significantly different between groups (9.3 vs. 11.8 mg/kg, p = 0.192). All doses were infused over 30 min every 24 h. Tobramycin elimination rate constant (0.510 vs. 0.493 h-1, p = 0.433) and volume of distribution (0.31 vs. 0.23 L/kg, p = 0.640) were not different between groups. No patient experienced acute kidney injury. Additionally, both groups experienced similar duration of tobramycin therapy (12.3 vs. 9.6 days, p = 0.184) and length of stay (12.0 vs. 12.6 days, p = 0.801).

No difference in tobramycin elimination rate constant was found between patients with PCD and those with CF. Clinical outcomes were not significantly different between groups. Although not statistically significant, a lower tobramycin dose was observed in patients with PCD.

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.

A 77-year-old man was referred to our department because of macrohematuria, oliguria, and a serum creatinine level of 2.47 mg/dL during boron neutron capture therapy (BNCT) for oropharyngeal cancer. At baseline, his creatinine level had been 0.98 mg/dL. The vital signs and physical examination were normal. A urinalysis showed protein and numerous red cells per high-power field, and needle-shaped crystals were observed. A plane computed tomography showed hematoma within the extensive ureter. However, hydronephrosis was not recognized. Immediate discontinuation of BNCT and supplemental fluids reduced gross hematuria, increased urine, and creatinine decreased to 0.97 mg/dL. BNCT is an innovative radiation therapy that targets tumor cells by inducing a nuclear reaction between 10B and neutrons within the tumor. However, there have been no reported cases of treatment-related boron crystals causing ureteral injury that leads to acute kidney injury, and oncologists should be aware of this potential risk.

This study aimed to investigate the efficacy and safety of intravenous colistin in pediatric patients with nosocomial Gram-negative bacteria infections and to determine factors associated with treatment outcomes.

This retrospective study recruited patients <18 years of age receiving intravenous colistin between January 2014 and December 2018. Clinical data and treatment outcomes were reviewed, and factors associated with treatment outcomes were assessed.

This study included 178 patients with a median age of 3.4 years (range, 0.1-17.8). The mean ± SD dose of colistin prescribed to patients without renal impairment was 5.1 ± 0.6 mg/kg/day. The clinical response rate was 70.8% in patients receiving colistin for specific treatment. Infection-related mortality and crude mortality were 17.5% and 19.7%, respectively. The nephrotoxicity rate was 29.8%; approximately 70% of the episodes occurred between the 3rd and 7th day of treatment. The presence of at least 2 organ dysfunctions [adjusted hazard ratio (aHR): 7.17; 95% CI: 1.64-31.40], septic shock (aHR: 2.69; 95% CI: 1.36-5.32) and receiving chemotherapy/immunosuppressants (aHR: 2.68; 95% CI: 1.36-5.25) were observed to be associated with clinical failure. The factors observed to be associated with nephrotoxicity included hypoalbuminemia (aHR: 2.93; 95% CI: 1.26-6.78), receiving amphotericin B (aHR: 2.29; 95% CI: 1.16-4.52), vancomycin (aHR: 3.36; 95% CI: 1.50-7.56) and vasopressors (aHR: 2.57; 95% CI: 1.27-5.21).

Colistin is generally effective in the treatment of nosocomial Gram-negative bacteria infections in pediatric patients. Close monitoring of renal function should be considered, especially in high-risk patients. Optimal dosage regimens for pediatric populations to promote more favorable clinical outcomes and minimize nephrotoxicity require further investigation.

Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM). Prerenal acute kidney injury (AKI) is associated with profound hypovolemia and reduced renal perfusion. Results regarding hyperchloremia-associated AKI in patients with DKA are conflicting; we therefore investigated the potential relationship between hyperchloremia status and the risk of developing AKI. This single-center cohort study included 113 newly diagnosed T1DM patients with DKA admitted to the pediatric intensive care unit. Laboratory parameters, including Na, K, urea, creatinine, and chloride levels, were retrospectively reviewed at the time of presentation and at 12, 24 and 36 h. AKI was defined using the eGFR according to the pediatric RIFLE classification criteria. Twenty-two (19.5%) of the 113 patients were in the AKI group. Two-way repeated-measures ANOVA showed significant (P values ≤ 0.01) time interaction effects within the groups based on the eGFR and the serum chloride, hyperchloremia, and phosphate levels. Serum chloride levels did not differ between the groups during the first 12 h (p > 0.05) but were significantly greater in the AKI group than in the non-AKI group at 24 h and 36 h (p < 0.01). The final DKA resolution time was significantly greater in the AKI group than in the non-AKI group [22.2 (9.5) vs. 17.0 (12.0) h, respectively; p = 0.03]. However, the groups had similar lengths of hospital stay [13.0 (8.0) days vs. 12.0 (4.0) days, respectively; p = 0.17].Conclusions: Hyperchloremia may be iatrogenic rather than causative during treatment. This may worsen renal failure and prolong the recovery and treatment time for DKA patients. What is Known? • Acute kidney injury resulting from severe volume depletion is a common occurrence in diabetic ketoacidosis and typically requires significant volume replacement therapy. • In recent years, hyperchloremia has been associated with increased risks of AKI, morbidity, and mortality in some conditions, such as diabetic ketoacidosis. What is New? • The incidence of hyperchloremia increases over time during the treatment of diabetic ketoacidosis. • Hyperchloremia may be an iatrogenic element rather than a cause of acute kidney injury during the treatment of diabetic ketoacidosis.

Several studies have shown that vancomycin combined with piperacillin/tazobactam (VPT) increased the risk of acute kidney injury (AKI) compared with other antibiotics in children. However, the epidemiology of VPT-associated AKI in children is unknown.

To evaluate the incidence and risk factors of VPT-associated AKI in children.

Literature databases of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, WanFang Database, and China Biology Medicine Disc were searched from inception to November 2023. References of included studies were also manually checked.

Two independent reviewers selected studies, extracted data, and quality assessment. Meta-analyses were performed to quantify the incidence and risk factors of VPT-associated AKI in children.

Sixteen cohort studies were identified. Overall, the incidence of VPT-associated AKI in children was 24.3% (95% CI: 17.9%-30.6%). The incidence of VPT-associated AKI in critically ill children (26.6%) was higher than that in noncritically ill children (10.9%). Moreover, higher serum vancomycin trough concentration (>15 mg/L), use of vasopressors, combination of nephrotoxins and intensive care unit admission were risk factors for VPT-associated AKI in children (P < 0.05).

Identifying high-risk groups and determining safer treatments is critical to reducing the incidence of VPT-associated AKI in children.

The incidence of VPT-associated AKI in children is high, especially in critically ill children. Medication regimens should be personalized based on the presence of individual risk factors. Moreover, renal function was regularly assessed throughout treatment with VPT.

The combination of vancomycin and piperacillin/tazobactam (V+P/T) is used for empirical antibiotic treatment of severe infections, especially in immunocompromised patients and those colonized with multidrug-resistant bacteria. Nephrotoxicity is a frequently observed adverse effect of vancomycin. Its risk can be reduced by therapeutic drug monitoring and adjusted dosing. Piperacillin/tazobactam (P/T) rarely causes interstitial nephritis. The results of retrospective cohort studies in children predominantly show a low, clinically irrelevant, additive nephrotoxicity (defined as an increase in creatinine in the serum) of both substances. Due to the limitations of the existing publications, the ABS working group of the DGPI and experts of the GPN do not recommend against the use of P/T plus vancomycin. Preclinical studies and a prospective study with adult patients, which evaluated different renal function tests as well as clinical outcomes, do not support previous findings of additive nephrotoxicity. Time-restricted use of V+P/T can minimize exposure and the potential risk of nephrotoxicity. Local guidelines, developed in collaboration with the antibiotic stewardship team, should define the indications for empirical and targeted use of P/T and V+P/T. When using combination therapy with V+P/T, kidney function should be monitored through clinical parameters (volume status, balancing, blood pressure) as well as additional laboratory tests such as serum creatinine and cystatin C.

Postoperative acute kidney injury (AKI) is a common complication that is associated with chronic kidney disease, early postsurgical mortality, and prolonged hospital stays. Preterm neonates who undergo surgery are at risk factors for AKI due to underdeveloped kidneys. To date, little is known about the incidence and perioperative risk factors for AKI in preterm neonates undergoing noncardiac surgery. Preterm neonates who underwent noncardiac surgery between January May 1, 2020, and February 28, 2023, were enrolled in the trial according to the inclusion criteria. Both multivariable and logistic regression analyses were used to analyze the associations between characteristic data and AKI. In total, 106 preterm neonates met the inclusion criteria, and 25 preterm neonates (23.6%) developed postoperative AKI. Multivariate analysis revealed that the factors associated with AKI were gestational age < 32 weeks [OR: 4.88; 95% CI (1.23-19.42)], preoperative sepsis [OR: 3.98; 95% CI (1.29-12.28)], and intraoperative hypotension [OR: 3.75; 95% CI (1.26-11.15)]. Preterm neonates who developed AKI were more likely to have longer hospital length of stays (38 [18,69] days vs. 21[12,46]) and higher medical costs (93,181.6 [620450.0,173,219.0] ￥ vs. 58,134.6 [31015.1,97,224,1) ￥ than neonates who did not develop AKI. Preterm neonates who underwent noncardiac surgery had a high incidence of AKI. Independent risk factors for AKI in preterm neonates who underwent noncardiac surgery were low gestational age, preoperative sepsis, and intraoperative hypotension. Preterm neonates who developed AKI were more likely to have longer hospital stays and higher medical costs.

Acute kidney injury (AKI) is a common and important complication of burn injury. Although there are numerous adult studies, data regarding AKI in pediatric burn patients are scarce. Here, we aimed to evaluate the frequency, clinical features, and prognosis of AKI among pediatric burn injury patients.

This is a retrospective cohort study. Patients aged between 1 month and 18 years who had been followed up between the years 2011 and 2017 were included, and patients with previous kidney disease were excluded. Demographic data, laboratory and clinical variables, management strategies, and outcome data were obtained from the hospital records. Factors associated with AKI were determined by logistic regression analysis.

A total of 697 patients had been followed up, and 87 (12.5%) had AKI. Older age, refugee status, prolonged duration between the incident and time of hospitalization, presence of sepsis, severity and type of burn, volume of fluid administration, intubation status, and accompanying organ failure were all associated with the development of AKI. According to multivariate logistic regression analysis, the most statistically significant factors associated with the development of AKI were older age and increased serum hemoglobin values. In terms of outcomes, length of stay and mortality increased in patients with AKI when compared with patients without AKI.

Similar to adults, AKI is an important and common complication of burn injury in pediatric burn patients and is associated with increased length of stay, morbidity, and mortality. Early recognition and prompt and appropriate management are crucial to avoid morbidity and mortality.

How to cite this article: Kumar V. VeXUS: Do Not Drown in the ExCESS. Indian J Crit Care Med 2024;28(5):419-421.

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.

The present study aimed to examine the effect of magnesium (Mg) supplementation on cisplatin-induced nephrotoxicity (CIN) in pediatric cancer patients.

The present phase-2, open-label, multicenter, randomized controlled trial enrolled patients aged less than 20 years who were scheduled to receive cisplatin-containing chemotherapy and randomly allocated them at a ratio of 1:1 to a Mg supplementation arm with even-numbered chemotherapy courses (arm AB) or another arm with odd-numbered courses (arm BA). Analysis objects were reconstructed into two groups depending on whether the chemotherapy course had Mg supplementation (group B) or not (group A). The primary outcome was the proportion of chemotherapy courses resulting in elevated serum creatinine per chemotherapy course. The secondary outcomes included efficacies evaluated using other biomarkers and the safety of the Mg supplementation.

Twenty-eight patients were randomly allocated to either group (16 to arm AB and 12 to arm BA). The baseline characteristics of the groups were similar. There was no significant difference in the proportion of courses with increased serum creatinine between the groups (group A: 10% vs. group B: 6%; P = 0.465) nor was any significant difference observed in other biomarkers during any chemotherapy course. The Mg value during chemotherapy was significantly higher in group B than that in group A. No adverse events related to magnesium administration were observed.

The study design, which treated a single chemotherapy course as a study object, failed to detect a statistically significant benefit of Mg supplementation for preventing CIN in pediatric cancer patients.

JRCT ( https://jrct.niph.go.jp/ ) Identifier UMIN000029215 jRCTs031180251. UMIN-CTR ( http://www.umin.ac.jp/icdr/index.html ) Identifier UMIN000029215.

Acute kidney injury requiring dialysis (AKI-D) commonly occurs in the setting of multiple organ dysfunction syndrome (MODS). Continuous renal replacement therapy (CRRT) is the modality of choice for AKI-D. Mid-term outcomes of pediatric AKI-D supported with CRRT are unknown. We aimed to describe the pattern and impact of organ dysfunction on renal outcomes in critically ill children and young adults with AKI-D.

Retrospective cohort.

Two large quarternary care pediatric hospitals.

Patients 26 y old or younger who received CRRT from 2014 to 2020, excluding patients with chronic kidney disease.

None.

Organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. MODS was defined as greater than or equal to two organ dysfunctions. The primary outcome was major adverse kidney events at 30 days (MAKE30) (decrease in estimated glomerular filtration rate greater than or equal to 25% from baseline, need for renal replacement therapy, and death). Three hundred seventy-three patients, 50% female, with a median age of 84 mo (interquartile range [IQR] 16-172) were analyzed. PELOD-2 increased from 6 (IQR 3-9) to 9 (IQR 7-12) between ICU admission and CRRT initiation. Ninety-seven percent of patients developed MODS at CRRT start and 266 patients (71%) had MAKE30. Acute kidney injury (adjusted odds ratio [aOR] 3.55 [IQR 2.13-5.90]), neurologic (aOR 2.07 [IQR 1.15-3.74]), hematologic/oncologic dysfunction (aOR 2.27 [IQR 1.32-3.91]) at CRRT start, and progressive MODS (aOR 1.11 [IQR 1.03-1.19]) were independently associated with MAKE30.

Ninety percent of critically ill children and young adults with AKI-D develop MODS by the start of CRRT. Lack of renal recovery is associated with specific extrarenal organ dysfunction and progressive multiple organ dysfunction. Currently available extrarenal organ support strategies, such as therapeutic plasma exchange lung-protective ventilation, and other modifiable risk factors, should be incorporated into clinical trial design when investigating renal recovery.

Cytomegalovirus (CMV) infection following allogeneic hematopoietic cell transplantation has considerable morbidity and mortality, and foscarnet is a treatment option that requires renal dose adjustment. Serum creatinine (SCr)-based estimated glomerular filtration rate (eGFR) equations are used to estimate renal function for patients receiving foscarnet, but cystatin C (cysC) has been shown as a possible alternative. Data examining cysC-based eGFR in this population is sparse. Our primary objective was to evaluate outcomes of patients treated with foscarnet dosed utilizing cysC-based eGFR versus SCr-based eGFR.

We analyzed patients on the transplantation and cellular therapies service at Memorial Sloan Kettering Kids from January 2011 to September 2021 who received allogeneic hematopoietic cell transplantation and ≥14 days of foscarnet for CMV infection. Patients with cysC-based eGFR were compared to a historical cohort of patients who only had SCr-based eGFR. Outcomes included time to CMV clearance, death or change in anti-CMV therapy. Cumulative incidence curves and cause-specific hazards model were used for analysis.

In 61 analyzed patients, no differences were found between the cohorts in cumulative incidence of change in anti-CMV therapy ( P = 0.17) or death ( P = 0.69). After adjustment for multiple confounders, patients in the SCr cohort seemed to have a higher chance of CMV clearance compared with the cysC cohort, but the difference was not statistically significant (hazard ratio = 2.42, P = 0.089). Patients who received corticosteroids appeared to have lower incidence of CMV clearance ( P = 0.056).

We did not find differences in outcomes when dosing foscarnet using cysC versus SCr for treatment of CMV infection.

The renal angina index (RAI) provides a clinically feasible and applicable tool to identify critically ill children at risk of severe acute kidney injury (AKI) in high-income countries. Our objective was to evaluate the performance of the RAI as a predictor of the development of AKI in children with sepsis in a middle-income country and its association with unfavorable outcomes.

This is a retrospective cohort study in children with sepsis hospitalized in the pediatric intensive care unit (PICU) between January 2016 and January 2020. The RAI was calculated 12 hours after admission to predict the development of AKI and at 72 hours to explore its association with mortality, the need for renal support therapy, and PICU stay.

We included 209 PICU patients with sepsis with a median age of 23 months (interquartile range, 7-60). We found that 41.1% of the cases (86/209) developed de novo AKI on the third day of admission (KDIGO 1, 24.9%; KDIGO 2, 12.9%; and KDIGO 3, 3.3%).Overall mortality was 8.1% (17/209), higher in patients with AKI (7.7% vs 0.5%, P < 0.01). The RAI on admission was able to predict the presence of AKI on day 3 (area under the curve (AUC), 0.87; sensitivity, 94.2%; specificity, 100%; P < 0.01), with a negative predictive value greater than 95%. An RAI greater than 8 at 72 hours was associated with a greater risk of mortality (adjusted odds ratio [aOR], 2.6; 95% confidence interval [CI], 2.0-3.2; P < 0.01), a need for renal support therapy (aOR, 2.9; 95% CI, 2.3-3.6; P < 0.01), and a PICU stay of more than 10 days (aOR, 1.54; 95% CI, 1.1-2.1; P < 0.01).

The RAI on the day of admission is a reliable and accurate tool for predicting the risk of developing AKI on day 3, in critically ill children with sepsis in a limited resource context. A score greater than eight 72 hours after admission is associated with a higher risk of death, the need for renal support therapy, and PICU stay.

Acute kidney injury (AKI) in children is associated with increased morbidity, reduced health-related quality of life, greater resource utilization, and higher mortality. Improvements in the timeliness and precision of AKI diagnosis in children are needed. In this report, we highlight existing, novel, and on-the-horizon diagnostic and risk-stratification tools for pediatric AKI, and outline opportunities for integration into clinical practice. We also summarize pediatric-specific high-risk diagnoses and exposures for AKI, as well as the potential role of real-time risk stratification and clinical decision support to improve outcomes. Lastly, the key characteristics of important pediatric AKI phenotypes will be outlined. Throughout, we identify key knowledge gaps, which represent prioritized areas of focus for future research that will facilitate a comprehensive, timely and personalized approach to pediatric AKI diagnosis and management.

The kidneys play a pivotal role in elimination of most drugs; therefore, a comprehensive understanding of renal physiology and pathology is important for those involved in drug development. High filtration capacity and metabolic activity make the kidneys vulnerable to drug-induced nephrotoxicity (DIN). Acute DIN may manifest on a background of renal impairment that has resulted from underlying disease, previously administered nephrotoxic medications, congenital renal abnormalities, or the natural aging process. The ability of the kidneys to compensate for DIN depends on the degree of pre-insult renal function. Therefore, it can be difficult to identify. The discovery and development of novel biomarkers that can diagnose kidney damage earlier and more accurately than current clinical measures and may be effective in detecting DIN. The goal of this manuscript is to provide a pragmatic and evidence-based supportive guidance for the early identification and management of DIN during the drug development process for clinical trial participants of all ages. The overall objective is to minimize the impact of DIN on kidney function and to collect renal safety data enabling risk analysis and mitigation.

Continuous renal replacement therapy (CRRT) is the preferred method for renal support in critically ill and hemodynamically unstable children in the pediatric intensive care unit (PICU) as it allows for gentle removal of fluids and solutes. The most frequent indications for CRRT include acute kidney injury (AKI) and fluid overload (FO) as well as non-renal indications such as removal of toxic metabolites in acute liver failure, inborn errors of metabolism, and intoxications and removal of inflammatory mediators in sepsis. AKI and/or FO are common in critically ill children and their presence is associated with worse outcomes. Therefore, early recognition of AKI and FO is important and timely transfer of patients who might require CRRT to a center with institutional expertise should be considered. Although CRRT has been increasingly used in the critical care setting, due to the lack of standardized recommendations, wide practice variations exist regarding the main aspects of CRRT application in critically ill children.     Conclusion: In this review, from the Critical Care Nephrology section of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC), we summarize the key aspects of CRRT delivery and highlight the importance of adequate follow up among AKI survivors which might be of relevance for the general pediatric community. What is Known: • CRRT is the preferred method of renal support in critically ill and hemodynamically unstable children in the PICU as it allows for gentle removal of fluids and solutes. • Although CRRT has become an important and integral part of modern pediatric critical care, wide practice variations exist in all aspects of CRRT. What is New: • Given the lack of literature on guidance for a general pediatrician on when to refer a child for CRRT, we recommend timely transfer to a center with institutional expertise in CRRT, as both worsening AKI and FO have been associated with increased mortality. • Adequate follow-up of PICU patients with AKI and CRRT is highlighted as recent findings demonstrate that these children are at increased risk for adverse long-term outcomes.

The standard of care for detecting acute kidney injury (AKI) is change in serum creatinine (SCr) and urine output, which are limited. This study aimed to compare urinary biomarkers neutrophil gelatinase-associated lipocalin (uNGAL) with kidney injury molecule-1 (uKIM-1) in critically ill children exposed to vancomycin who did and did not develop AKI as defined by changes in SCr.

Single-center, prospective, clinical, observational cohort study.

Tertiary care children's hospital in an urban setting.

Children aged 0 (corrected gestational age 42 weeks) to 18 years admitted to the intensive care unit who received vancomycin were included.

None.

The primary outcome was mean change in uNGAL and uKIM-1 between AKI and no-AKI groups. AKI was defined as a minimum 50% increase in SCr from baseline over a 48 h period, within 7 days of first vancomycin exposure. Three urine samples were collected: baseline (between 0 and 6 h of first vancomycin dose), second (18-24 h after the "baseline"), and third (18-24 h after the second sample). Concentrations of uKIM-1 and uNGAL were measured in each sample.

Forty-eight children (52% male; median age 6 years) were included. Eight (16.7%) children developed AKI. Mean changes in uNGAL (713.196 ± 1,216,474 vs. 16.101 ± 37.812 pg/mL; p = 0.0004) and uKIM-1 (6060 ± 11.165 vs. 340 ± 542 pg/mL; p = 0.0015) were greater in children with AKI versus no-AKI, respectively.

uNGAL and uKIM-1 concentrations increased significantly more in critically ill children with AKI compared with those with no-AKI during the first 48-72 h of vancomycin exposure and may be useful as prospective biomarkers of AKI.

Acute kidney injury (AKI) is a frequent complication of children admitted to the paediatric intensive care unit. One key management modality of AKI is the use of diuretics to reduce fluid overload. Aminophylline, a drug that is well known for its use in the treatment of bronchial asthma, is also purported to have diuretic effects on the kidneys. This retrospective cohort study assesses the effect of aminophylline in critically ill children with AKI.

A retrospective chart review of children admitted to the paediatric intensive care unit of the Red Cross War Memorial Children's Hospital (RCWMCH) with AKI who received aminophylline (from 2012 to June 2018) was carried out. Data captured and analyzed included demographics, underlying disease conditions, medications, urine output, fluid balance, and kidney function.

Data from thirty-four children were analyzed. Urine output increased from a median of 0.4 mls/kg/hr [IQR: 0.1, 1.1] at six hours prior to aminophylline administration to 0.6 mls/kg/hr [IQR: 0.2, 1.9] at six hours and 1.6 mls/kg/hr [IQR:0.2, 4.2] at twenty-four hours post aminophylline therapy. The median urine output significantly varied across the age groups over the 24-h time period post-aminophylline, with the most response in the neonates. There was no significant change in serum creatinine levels six hours post-aminophylline administration [109(IQR: 77, 227)-125.5(IQR: 82, 200) micromole/l] P-value = 0.135. However, there were significant age-related changes in creatinine levels at six hours post-aminophylline therapy.

Aminophylline increases urine output in critically ill children with AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Acute kidney injury (AKI) is a commonly reported adverse effect of administration of antimicrobials. While AKI can be associated with poorer outcomes, there is little information available to understand rates of AKI in children exposed to various antimicrobials. We performed a structured review using the PubMed and Embase databases. Articles were included if they provided an AKI definition in patients who were < 19 years of age receiving an antimicrobial and reported the frequency of AKI. Author-defined AKI rates were calculated for each study and mean pooled estimates for each antimicrobial were derived from among all study participants. Pooled estimates were also derived for those studies that reported AKI according to pRIFLE (pediatric risk, injury, failure, loss, end stage criteria), AKIN (acute kidney injury network), or KDIGO (kidney disease improving global outcomes) creatinine criteria. A total of 122 studies evaluating 28 antimicrobials met the inclusion criteria. Vancomycin was the most commonly studied drug: 11,514 courses across 44 included studies. Among the 27,285 antimicrobial exposures, the overall AKI rate was 13.2% (range 0-42.1% by drug), but the rate of AKI varied widely across studies (range 0-68.8%). Cidofovir (42.1%) and conventional amphotericin B (37.0%) had the highest pooled rates of author-defined AKI. Eighty-one studies used pRIFLE, AKIN, or KDIGO AKI criteria and the pooled rates of AKI were similar to author-defined AKI rates. In conclusion, antimicrobial-associated AKI is reported to occur frequently in children, but the rates of AKI varies widely across studies and drugs. Most published studies examined hospitalized patients and heterogeneity in study populations and in author definitions of AKI are barriers to a comparison of nephrotoxicity risk among antimicrobials in children.

Acute Kidney Injury (AKI) in the Intensive Care Unit (ICU) have concepts of diagnosis and management have water balance as their main point of evaluation. In our ICU, from 2004 to 2012, the nephrologist's participation was on demand only; and as of 2013 their participation became continuous in meetings to case discussion. The aim of this study was to establish how an intense nephrologist/intensivist interaction influenced the frequency of dialysis indication, fluid balance and pRIFLE classification during these two observation periods.

Retrospective study, longitudinal evaluation of all children with AKI undergoing dialysis (2004 to 2016).

frequency of indication, duration and volume of infusion in the 24 hours preceding dialysis; diuresis and water balance every 8 hours. Non-parametric statistics, p ≤ 0.05.

53 patients (47 before and 6 after 2013). There were no significant differences in the number of hospitalizations or cardiac surgeries between the periods. After 2013, there was a significant decrease in the number of indications for dialysis/year (5.85 vs. 1.5; p = 0.000); infusion volume (p = 0.02), increase in the duration of dialysis (p = 0.002) and improvement in the discrimination of the pRIFLE diuresis component in the AKI development.

Integration between the ICU and pediatric nephrology teams in the routine discussion of cases, critically approaching water balance, was decisive to improve the management of AKI in the ICU.

Acute kidney injury (AKI) is caused by a sudden loss of renal function, resulting in the build-up of waste products and a significant increase in mortality and morbidity. It is commonly diagnosed in critically ill patients, with its occurrence estimated at up to 50% in patients hospitalized in the intensive critical unit. Despite ongoing efforts, the death rate associated with AKI has remained high over the past half-century. Thus, it is critical to investigate novel therapy options for preventing the epidemic. Many studies have found that inflammation and Toll-like receptor-4 (TLR-4) activation have a significant role in the pathogenesis of AKI. Noteworthy, challenges in the search for efficient pharmacological therapy for AKI have arisen due to the multifaceted origin and complexity of the clinical history of people with the disease. This article focuses on kidney injury's epidemiology, risk factors, and pathophysiological processes. Specifically, it focuses on the role of TLRs especially type 4 in disease development.

This retrospective study aimed to determine the incidence, risk factors, and outcomes of acute kidney injury (AKI) in neonates following the arterial switch operation (ASO) for transposition of great arteries (TGA).

Retrospective review of medical data of children who underwent ASO in 2019-2020 in the Ukrainian Children's Cardiac Center.

76 consecutive neonatal patients were included, 48 developed AKI after ASO (51.7%), and 24 - had severe AKI (25.8%). Severe AKI development was associated with longer cross-clamp time: 82 (61-127) versus 73.5 (53-136) in the non-severe AKI group (p = 0.02). 76 min of cross-clamp time were defined as a threshold value for increased severe AKI risk, OR 4.4 (95% CI: 1.5 - 13, p = 0.01). Higher lactate levels during cardiopulmonary bypass (CPB) increased severe AKI development risk, OR 1.5 (95% CI: 1.0 - 2.0, p = 0.03). Children with severe AKI had prolonged mechanical ventilation, longer time to negative fluid balance, and higher postoperative day 3 (POD3) Inotropic Score (IS). Only one patient required peritoneal dialysis.

In our study, 51.7% of patients developed AKI after ASO, 25.8%-severe AKI. Prolonged cross-clamp time and higher lactate levels during cardiopulmonary bypass increased the risk for severe AKI development. The development of AKI was associated with prolonged mechanical ventilation, longer time to negative fluid balance, higher POD 3 Inotropic Score.

Acute kidney injury (AKI) has been associated with higher mortality and morbidity in trauma victims. There is a paucity of information regarding the outcomes of severe AKI (sAKI) in pediatric trauma patients. Therefore, the trauma quality improvement program database (TQIP) was used to assess that hypothesis sAKI will be associated with higher mortality among pediatric trauma patients.

The TQIP database was accessed for the study. Patients aged <18 years old admitted to the hospital after sustaining injury were included in the study. Demographics, injury severity score (ISS) and Glasgow coma scale (GCS) score, other body regions injuries, and available comorbidities were included in the study. Propensity score matching analysis was performed to compare the two groups, sAKI vs. no sAKI on patients' characteristics and outcomes. All p values are two-sided. A p-value <0.05 is considered statistically significant.

Out of 139,832 patients who qualified for the study, 106 (0.1%) patients suffered from sAKI. Pair-matched analysis showed no significant difference between the groups, sAKI, and no sAKI, regarding the in-hospital mortality (14.3% vs. 12.4%, P = 0.838). There was a prolonged hospital length of stay in the sAKI group when compared to the no sAKI group, (27 days [21-33] vs. 10 [9-14], P < 0.001). There was a higher incidence of deep vein thrombosis (DVT) (12.4% vs. 2.9%, P = 0.024) in the sAKI group as well.

The sAKI patients stayed in the hospital approximately three times longer and had a 4-fold increase in the occurrence of DVT. No significant difference was found between the groups in in-hospital mortality.

Retrospective cohort study.

This study aims to clarify the risk of nephrotoxicity with intravenous use of acyclovir (ACV) for the treatment of neonates (ages <3 months) and children (ages ≥3 months to <12 years) with herpes simplex virus (HSV) infections and to identify gaps in knowledge that could be further investigated.

Multiple databases were searched to identify studies on risk of nephrotoxicity with ACV use for treatment of invasive HSV infections, defined as any neonatal infection or HSV encephalitis (HSE) in children.

There were 5 and 14 studies that evaluated the risk of ACV-associated nephrotoxicity in neonates and children, respectively. The US Food and Drug Administration (FDA) delayed the approval of high (HD; 60 mg/kg/day) ACV in neonates secondary to risk of toxicity. Based on our review, the risk of ACV-associated nephrotoxicity was lower in the neonatal compared with the pediatric population. Acyclovir dose >1500 mg/m2, older age, and concomitant use of nephrotoxic drugs were identified as variables that increased the risk of ACV nephrotoxicity in children. Although the FDA has approved the use of HD ACV for the treatment of HSE in children, the American Academy of Pediatrics recommends a lower dose to minimize the risk of toxicity. The efficacy and safety of high vs lower doses of ACV for the management of HSE in children has yet to be evaluated.

The risk of ACV-associated nephrotoxicity was lower among neonates compared with older children. Future studies are needed to identify the optimal dosage that minimizes toxicities and maximizes the efficacy of ACV in children with HSE.

Vancomycin 24-hour area under the curve over minimum inhibitory concentration (AUC/MIC) monitoring has been recommended over trough-based monitoring in pediatric patients. This study compared the proportion of target attainment between vancomycin AUC/MIC and trough-based methods, and identified risk factors for subtherapeutic initial extrapolated targets.

This was a retrospective, observational study conducted at KK Women's and Children's Hospital (KKH), Singapore. Patients aged 1 month to 18 years with stable renal function who received intravenous vancomycin between January 2014 and October 2017, with at least 2 vancomycin serum concentrations obtained after the first dose of vancomycin, were included. Using a pharmacokinetic software, namely Adult and Pediatric Kinetics (APK), initial extrapolated steady-state troughs and 24-hour AUC were determined by using a one-compartmental model. Statistical tests included Wilcoxon rank sum test, McNemar test, logistic regression, and classification and regression tree (CART) analysis.

Of the 82 pediatric patients included, a significantly larger proportion of patients achieved therapeutic targets when the AUC/MIC-based method (24, 29.3%) was used than with the trough-based method (9, 11.0%; p < 0.01). Patients with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 or with age <13 years had an increased risk of obtaining subtherapeutic targets. However, empiric vancomycin doses of 60 mg/kg/day would be sufficient to achieve serum therapeutic targets, using the AUC/MIC-based method.

The AUC/MIC-based vancomycin monitoring may be preferred because a larger proportion of patients could achieve initial therapeutic targets. Future prospective studies with larger sample size will be required to determine the optimal vancomycin strategy for pediatric patients.

Severity of acute kidney injury (AKI) confers higher odds of mortality. Timely recognition and early initiation of preventive measures may help mitigate the injury further. Novel biomarkers may aid in the early detection of AKI. The utility of these biomarkers across various clinical settings in children has not been evaluated systematically.

To synthesize the currently available evidence on different novel biomarkers for the early diagnosis of AKI in pediatric patients.

We searched four electronic databases (PubMed, Web of Science, Embase, and Cochrane Library) for studies published between 2004 and May 2022.

Cohort and cross-sectional studies evaluating the diagnostic performance of biomarkers in predicting AKI in children were included.

Participants in the study included children (aged less than 18 years) at risk of AKI.

We used the QUADAS-2 tool for the quality assessment of the included studies. The area under the receiver operating characteristics (AUROC) was meta-analyzed using the random-effect inverse-variance method. Pooled sensitivity and specificity were generated using the hierarchical summary receiver operating characteristic (HSROC) model.

We included 92 studies evaluating 13,097 participants. Urinary NGAL and serum cystatin C were the two most studied biomarkers, with summary AUROC of 0.82 (0.77-0.86) and 0.80 (0.76-0.85), respectively. Among others, urine TIMP-2*IGFBP7, L-FABP, and IL-18 showed fair to good predicting ability for AKI. We observed good diagnostic performance for predicting severe AKI by urine L-FABP, NGAL, and serum cystatin C.

Limitations were significant heterogeneity and lack of well-defined cutoff value for various biomarkers.

Urine NGAL, L-FABP, TIMP-2*IGFBP7, and cystatin C showed satisfactory diagnostic accuracy in the early prediction of AKI. To further improve the performance of biomarkers, they need to be integrated with other risk stratification models.

PROSPERO (CRD42021222698). A higher resolution version of the Graphical abstract is available as "Supplementary information".

Hospitalized children with acute kidney injury (AKI) have not been extensively studied for clinical outcomes including hospital stay, the need for mechanical ventilation, mortality rates, and healthcare utilization. We hypothesize significant financial costs and increased morbidity and mortality associated with pediatric AKI.

This is a retrospective study of pediatric patients (age ≤18 years) included in the Kids' Inpatient Database (KID) between January 1, 2016, and December 31, 2021. The results of the data analysis were utilized for comparative testing between the AKI and non-AKI cohorts.

The study included 4842 children [with AKI (n = 2424) and without AKI (n = 2418)]. The odds of mortality (p = 0.004) and mechanical ventilation (p < 0.001) were observed to be significantly higher among those with AKI as compared to those without AKI. Additionally, the median (IQR) duration of stay in the hospital (p < 0.001) and total cost (p < 0.001) were significantly higher among those with AKI vs. those without AKI.

AKI in children was associated with higher odds of mortality, longer duration of hospital stay, increased requirement of mechanical ventilation, and increased hospital expenditure. The scientific community can utilize this information to better understand the outcomes associated with this disease process in this patient population.

This article has thoroughly evaluated epidemiologic data associated with pediatric acute kidney injury (AKI) in hospitalized patients This study assesses mortality, hospital expenditure, and other factors to strengthen single-center and few multi-center studies and provides novel data regarding insurance and cost associated with pediatric AKI With increased knowledge of current epidemiology and risk factors, the scientific community can better understand prevention and outcomes in hospitalized children with AKI.