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Background 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. Objective To synthesize the currently available evidence on different novel biomarkers for the early diagnosis of AKI in pediatric patients. Data sources We searched four electronic databases (PubMed, Web of Science, Embase, and Cochrane Library) for studies published between 2004 and May 2022. Study eligibility criteria Cohort and cross-sectional studies evaluating the diagnostic performance of biomarkers in predicting AKI in children were included. Participants and interventions Participants in the study included children (aged less than 18 years) at risk of AKI. Study appraisal and synthesis methods 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. Results 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 Limitations were significant heterogeneity and lack of well-defined cutoff value for various biomarkers. Conclusions and implications of key findings 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. Systematic review registration PROSPERO (CRD42021222698). Graphical Abstract, Author(s): Jitendra Meena [sup.1] , Christy Catherine Thomas [sup.2] , Jogender Kumar [sup.3] , Georgie Mathew [sup.4] , Arvind Bagga [sup.1] Author Affiliations: (1) grid.413618.9, 0000 0004 1767 6103, Division [...]

Background One-third of children with type 1 diabetes mellitus manifest with diabetic ketoacidosis (DKA). Most children presenting with DKA are in a volume-depleted state, leading to acute kidney injury (AKI). Besides volume depletion, hyperglycemia can induce tubular injury and kidney inflammation. Therefore, a thorough knowledge of incidence of AKI, risk factors, and outcomes in pediatric DKA is desirable to improve its management and outcomes. Objective To synthesize currently available evidence on the incidence, risk factors, and outcomes of AKI in children with DKA. Data sources We searched three electronic databases (EMBASE, PubMed, and Web of Science) from inception to September 2022 for original studies reporting AKI in children with DKA. Search strategies for the individual databases were drafted using free text words and MeSH incorporating 'acute kidney injury' and 'diabetic ketoacidosis.' Study eligibility criteria Cohort and cross-sectional studies reporting AKI in children with type 1 DM and DKA were included. Participants and interventions Children (aged less than 18 years) with type 1 DM and DKA. Study appraisal and synthesis methods The critical appraisal tool of NHLBI for cohort studies was used to assess the quality of the studies. We estimated the pooled incidence of AKI with 95% CI in children with DKA using a random effects model. The primary outcome was the pooled incidence of AKI during the DKA episodes. Results Twenty-one studies assessing 4087 children (4500 DKA episodes) reported AKI during DKA episodes. The pooled incidence of any stage of AKI during the DKA episode was 47% (95% CI: 40 to 55). Severe AKI was observed in 28% (21 to 35) of DKA episodes; however, only 4% (1 to 11%) of children with AKI received dialysis. Low serum bicarbonate, low corrected sodium, higher blood sugar, and high blood urea nitrogen at presentation have been reported to be associated with the development of AKI. Conclusion AKI developed in almost half of the DKA episodes, and every fourth DKA episode was associated with severe AKI. The recovery rate from DKA-associated AKI appears to be high; however, further studies are needed to assess the exact impact of AKI on long-term outcomes. Registration PROSPERO (CRD42022303200). Graphical abstract, Author(s): Jitendra Meena [sup.1] , Jaivinder Yadav [sup.2] , Jogender Kumar [sup.2] , Lesa Dawman [sup.2] , Karalanglin Tiewosh [sup.2] , Aliza Mittal [sup.1] , Rakesh Kumar [sup.2] , Devi [...]

Early recognition of patients at risk for severe acute kidney injury (AKI) by renal angina index (RAI) may help in the early institution of preventive measures. Objective was to evaluate performance of RAI alone or in combination with biomarkers in predicting severe AKI (KDIGO stage 2 and 3 or equivalent) and receipt of kidney replacement therapy (KRT) in critically ill children. We searched PubMed, EMBASE, Web of Sciences, and CENTRAL for studies published till May 2021. Search terms included acute kidney injury, pediatrics, adolescent, renal angina index, and biomarker. Proceedings of relevant conferences and references of included studies were also scrutinized. Two reviewers independently assessed the study eligibility. Cohort and cross-sectional studies evaluating the diagnostic performance of RAI in predicting AKI or receipt of KRT in children were included. Eligible participants were the children less than 18 years with RAI assessment on day 0 ofadmission. We followed PRISMA-DTA guidelines and used the QUADAS-2 tool for quality assessment. A bivariate model for meta-analysis was used to calculate the summary estimates of diagnostic parameters. Major outcomes were the diagnostic accuracy of RAI ([greater than or equal to] 8) alone or with biomarkers in predicting severe AKI and KRT receipt. Diagnostic accuracy was reported using summary sensitivity, specificity, and area under the curve (AUC). Overall, 22 studies (24 reports, 14,001 participants) were included. RAI [greater than or equal to] 8 on day 0 has summary sensitivity, specificity, and AUC of 0.86 (95% CI, 0.77-0.92), 0.77 (0.68-0.83), and 0.88 (0.85-0.91) respectively for prediction of severe AKI on day 3. In comparison, a combination of RAI and urinary neutrophil gelatinase-associated lipocalin (NGAL) showed summary sensitivity, specificity, and AUC of 0.76 (0.62-0.85), 0.89 (0.74-0.96), and 0.87 (0.84-0.90) respectively for predicting severe AKI. The sensitivity, specificity, and AUC of RAI for predicting receipt of KRT were 0.82 (0.71-0.90), 0.74 (0.66-0.81), and 0.85 (0.81-0.88) respectively. In meta-regression, only the study setting (sepsis vs. heterogenous) was associated with heterogeneity. We observed substantial heterogeneity among eligible studies. Five studies had concerns in patient selection, and seven studies also had applicability concerns in patient selection for this review. Moderate certainty evidence showed that RAI [greater than or equal to] 8 has good predicting ability in recognizing children at risk of severe AKI and receipt of KRT. The combination of urinary NGAL and RAI further improves the predicting ability (low-certainty evidence). Further studies are required on the context-driven assessment of novel biomarkers in the early prediction of AKI in RAI-positive children. Systematic review registration number: CRD4202122268. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information, Author(s): Jitendra Meena [sup.1] , Jogender Kumar [sup.2] , Christy Cathreen Thomas [sup.3] , Lesa Dawman [sup.1] , Karalanglin Tiewsoh [sup.1] , Menka Yadav [sup.4] , Georgie Mathew [sup.5] Author [...]

Aim: To synthesize the evidence on the effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) in adolescents with overweight or obesity. Materials and Methods: For this systematic review and network meta‐analysis, we searched five databases and registries until 2 March 2024 for eligible randomized controlled trials (RCTs). The primary outcome was weight change. We did a pairwise meta‐analysis to compare GLP‐1RAs and placebo, followed by a drug‐wise network meta‐analysis (NMA) to compare GLP‐1RAs against each other. Results: We screened 770 records to include 12 RCTs with 883 participants. The evidence suggests that GLP‐1RAs reduced weight (mean difference −4.21 kg, 95% confidence interval [CI] −7.08 to −1.35) and body mass index (BMI; mean difference −2.11 kg/m2, 95% CI −3.60 to −0.62). The evidence on waist circumference, body fat percentage and adverse events (AEs) was very uncertain. The results remained consistent with subgroup analyses for coexisting type 2 diabetes. Longer therapy duration led to a greater reduction in weight and BMI. In the NMA, semaglutide led to the greatest weight reduction, followed by exenatide, liraglutide and lixisenatide. Conclusions: The evidence suggests that GLP‐1RAs reduce most weight‐related outcomes in adolescents, with semaglutide being the most efficacious. There is uncertain evidence on body fat and serious AEs, probably due to fewer studies and low incidence, respectively. Larger RCTs with head‐to‐head comparisons, pragmatic design, adiposity‐related outcomes, and economic evaluation can further guide the use and choice of GLP‐1RAs. [ABSTRACT FROM AUTHOR]

To generate normative data and validate the recently developed, gender-neutral, External Genitalia Score (EGS) in Indian preterm and term neonates and children up to 2 years of age with normal and atypical genitalia. This observational study included 1,040 neonates born between 28 and 42 weeks of gestation and 152 children between 1 and 24 months of age. In addition, 50 children with disorders of sex development (DSD) were also enrolled in the study. The Prader stage/external masculinization score (EMS) (as applicable), anogenital ratio (AGR) and EGS were assessed for all neonates and children with typical and atypical genitalia. Median EGS values in newborn males with typical genitalia were 9.5 at 28–31 weeks, 10.5 at 32–33 weeks, 11 at 34 weeks and 11.5 in males at 35–42 weeks of gestation. For all females with typical genitalia, the EGS was 0. EMS and EGS showed a positive correlation in males with typical genitalia (r=0.421, p=0.000**) and all children with DSD (r=0.857, p=0.000**). Mean AGR in males and females with typical genitalia and those with DSD were 0.52±0.07, 0.31±0.05 and 0.47±0.13, respectively. EGS correlated with AGR in all males with typical genitalia (r=0.107, p=0.008**), and in all children with DSD (r=0.473, p=0.001**). The EGS enables accurate, gender-neutral and comprehensive assessment of external genitalia in Indian neonates and children with typical and atypical genitalia/DSD. Evaluation for DSD is recommended in any child with EGS greater than 0 and ≤10th percentile for gestation or age (10.5 in a term neonate). [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE: There is a paucity of pooled synthesized data on the epidemiology of neonatal acute kidney injury (AKI). Our objective with this study is to systematically assess the worldwide incidence of AKI in neonates. METHODS: We searched 3 electronic databases (Embase, PubMed, Web of Sciences) from January 2004 to December 2022 without language restrictions. We included cohort and cross-sectional studies that reported the incidence of AKI or associated mortality in neonates. Eligible studies had at least 10 participants and used standard criteria (Acute Kidney Injury Network/Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease (pRIFLE)/ Kidney Disease Improving Global Outcomes) to define AKI. Two authors independently retrieved data on demographic characteristics, clinical setting, and outcomes (incidence and AKI-associated mortality) using a semi-structured proforma and assessed the risk of bias. We used a random-effects metaanalysis to calculate pooled estimates with 95% confidence intervals. RESULTS: We included 201 studies (98 228 participants) from 45 countries. The incidence of any stage AKI was 30% (95% confidence interval 28-32), and that of severe AKI was 15% (14-16). Overall, AKI-associated mortality was 30% (27-33). The odds of mortality were higher (odds ratio 3.4; 2.9-4.0) in neonates with AKI compared with those without AKI. We found that perinatal asphyxia, sepsis, patent ductus arteriosus, necrotizing enterocolitis, and nephrotoxic medications were significant risk factors for AKI. Significant heterogeneity in the pooled estimates was a limitation of this study. CONCLUSIONS: AKI was observed in one-third of the neonates and was associated with increased risk of mortality. The incidence of AKI was almost similar in neonates with perinatal asphyxia and sepsis, but mortality was higher in the former group. [ABSTRACT FROM AUTHOR]