Search

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 [...]

Background Reports on long-term complications of childhood-onset nephrotic syndrome (NS), such as obesity, osteoporosis, growth failure, and hypertension, are mostly from developed countries not representing South Asian ethnicities. Furthermore, data on cardiovascular health among patients with childhood-onset NS are limited. Methods This was an observational study involving patients attending a tertiary care center. Patients aged 15 years and older were examined for long-term complications and remission of NS at their visit in December 2021. Childhood-onset NS meant onset of NS before 10 years of age. Long-term complications included obesity, growth failure, low bone mineral density (BMD) Z score, hypertension, and increased carotid intima-media thickness (cIMT). Long-term remission was defined as no relapse for the last [Formula omitted] 3 consecutive years without immunosuppressive medication to maintain remission. Results Of 101 patients studied (~ 80% with frequent relapsing (FR)/steroid-dependent (SD) NS), the mean age was 17.6 (± 2.4) years at the time of study. Long-term complications were noted in 89.1% of patients which included one or more of the following: obesity (22.7%), growth failure (31.7%), low BMD Z score (53.5%), hypertension (31.7%), and high cIMT (50.5%). Thirty-nine patients (38.6%) were in long-term remission at the time of the study. Growth failure and low BMD Z scores were less frequent in patients with long-term remission compared to those without long-term remission. Conclusions In patients with childhood-onset NS (predominantly FR/SDNS) who were studied at [Formula omitted] 15 years of age, ~ 90% had long-term complications which included high cIMT in 50%. Only ~ 40% were in long-term remission. Graphical abstract, Author(s): Joyita Bharati [sup.1] , Karalanglin Tiewsoh [sup.2] , Lesa Dawman [sup.2] , Tarvinder Singh [sup.3] , Ujjwal Gorsi [sup.3] , Arun Prabhahar Rajarajen [sup.1] , Aakanksha Sharma [sup.1] , [...]

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 [...]

Background: Enhanced availability of high-throughput sequencing (at progressively reducing costs) has revolutionized the identification of monogenic SRNS. However, in resource-poor settings, it may not be possible to perform next-generation sequencing (NGS) in all children wherein monogenic SRNS is suspected. Besides, the optimal strategy of genetic evaluation (in patients with SRNS) in routine clinical practice in resource-limited settings is unknown. Methods: Patients with newly diagnosed SRNS were recruited from our center and followed up prospectively. We analyzed the factor(s) independently predicting the occurrence of disease-causing variants in these patients. Results: In our study, 36 children/adolescents with SRNS were included (initial steroid resistance in 53%). On targeted NGS, pathogenic/likely pathogenic variants were identified in 31% (n = 11). These included homozygous or compound heterozygous variants in the following genes: ALOX12B, COL4A3, CRB2, NPHS1, NPHS2, PLCE1, and heterozygous variant in WT1 gene. Overall, 14 variants were identified of which 5 (36%) were novel. Age of < 1 or < 2 years and presence of family history of nephrotic syndrome independently predicted the occurrence of monogenic SRNS on multivariate analysis. Conclusions: While NGS-based genetic testing in SRNS is increasingly being incorporated in routine clinical practice the world over, the scenario is far from optimal in resource-limited settings. Our study highlights that resources for genetic testing in SRNS should be prioritized for patients with early age at disease onset and presence of family history. Larger studies composed of diverse multi-ethnic cohorts of patients with SRNS are required to further delineate the optimal strategy of genetic evaluation in resource-poor settings. [ABSTRACT FROM AUTHOR]