Prognostic Study Of AKI In Children And Proteomics Study On Contrast-induced AKI

Part I: Prognostic study of AKI in children(1)Epidemiology and prognosis of acute kidney injury and acute kidney disease in hospitalized childrenObjective: Acute Kidney Injury(AKI)is a common acute and critical condition among hospitalized children.Acute Kidney Disease(AKD)refers to acute or subacute renal impairment and/or declined renal function lasting 7 to 90 days following AKI.The prognosis of AKD includes recovery,recurrence of AKI,deterioration,or death.Few studies have investigated the prognosis of AKI and the epidemiology and prognosis of AKD in hospitalized children.This study aimed to explore the incidence and risk factors of AKI and AKD in children,and the impact of AKD on30-and 90-day adverse outcomes in hospitalized children with AKI.Methods: We conducted a retrospective study of AKI patients aged 1month to 18 years who were hospitalized to The Second Xiangya Hospital of Central South University between 2015 and 2020.The study utilized MAKE30(Major Adverse Kidney Events within 30 days)and 90-day adverse outcomes as primary outcome indicators.Multivariate logistic regression analysis was employed to assess the association between AKD staging and 30-and 90-day adverse outcomes.Risk factors for AKD were also explored.Results: Among 1394 pediatric AKI patients,the incidence of MAKE30 and 90-day adverse outcomes was 24.1% and 8.1%,respectively.AKD occurred in 42.3% of 1394 pediatric AKI patients,including: 186 patients with AKD stage 1,107 patients with AKD stage 2,and 126 patients with AKD stage 3.Pediatric patients with AKD stage 2-3 had a significantly higher rate of adverse outcomes at 30 and 90 days than pediatric patients with AKD stage 0 or AKD stage 1.AKD stage 2-3 was the strongest predictor of 30-adverse outcomes,with an adjusted odds ratio of 12.18,and it also increased the risk of adverse outcomes at 90 days by2.49 times compared to AKD stage 0.Glomerulonephritis and AKD stage2-3 were significant predictors of AKD stage 2-3.Conclusion: We determined the incidence and prognosis of AKI in hospitalized children.We also found a high incidence of AKD in hospitalized children with AKI.AKD stage 2-3 identified a high-risk subgroup among survivors of pediatric AKI and was independently associated with 30-and 90-day adverse outcomes.Adequate understanding of the potential risks and risk factors related to AKD stage 2-3 may help clinicians closely monitor these patients and promptly intervene to improve the adverse prognosis.(2)A study of a machine learning-based prognostic model for predicting acute kidney injury outcomes in hospitalized childrenObjective: The prognosis of AKI in children is adverse,and prognosis-related studies are limited.This study aimed to develop a machine learning-based prediction model for AKI outcomes in hospitalized children.Methods: We conducted a retrospective study of 1,394 AKI patients as described above.The study utilized MAKE30(Major Adverse Kidney Events within 30 days)and 90-day adverse outcomes as primary outcome indicators.Prediction models for MAKE30 and 90-day adverse outcomes were developed using the state-of-the-art machine learning algorithm XGBoost and traditional logistic regression.The performance of the models was evaluated by cross-validation.Results: The AUCs for MAKE30 and 90-day adverse outcomes in the XGBoost model for the 1394 pediatric AKI patients included were 0.810(95% CI: 0.763-0.857)and 0.851(95% CI: 0.785-0.916),respectively,and the AUCs for MAKE30 and 90-day adverse outcomes in the logistic regression model were 0.786(95% CI: 0.731-0.841)and 0.759(95% CI:0.654-0.864),respectively.Conclusion: This study is the first to develop a machine learningbased prediction model for 30-and 90-day adverse outcomes of AKI in hospitalized children using the XGBoost algorithm.The model performed well in predicting adverse outcomes of MAKE30 and 90 days.We developed a risk calculator webpage for this model,which is intended to assist clinical practitioners in determining the prognosis of children with AKI.Part II: Establishment of a new model of AKI in adolescent rats induced by iodinated contrast agents and its renal tissue proteomics studyObjective: Contrast-induced acute kidney injury(CI-AKI)is currently the third leading cause of hospital-acquired AKI,and its pathogenesis is still unclear and lacks specific treatment.The existing rat models of CIAKI have some drawbacks.The aim of this study was to develop a novel rat model of CI-AKI and to identify potential therapeutic targets for CIAKI using proteomic techniques.Methods and results: By comparing the effects of different interventions administered at various time points and durations of water abstinence on contrast-induced acute kidney injury(CI-AKI)in unilaterally nephrectomized rats,we found the following: Twenty-four hours of water abstinence two weeks after unilateral nephrectomy,followed by furosemide-induced dehydration and contrast injection,significantly induced renal tissue damage and renal dysfunction.Compared to other CI-AKI models involving nephrectomy,this new model required less time to prepare.Using this new model,we found that iohexol caused significantly greater declines in renal function,more severe renal tissue damage,and more marked changes in mitochondrial ultrastructure than iodixanol.Proteomic analysis of kidney tissues from control rats and rats in the new CI-AKI model identified 604 differentially expressed proteins.These proteins were enriched for the complement and coagulation cascades,COVID-19 pathways,PPAR signaling pathways,mineral uptake,cholesterol metabolism,ferroptosis,Staphylococcus aureus infection,systemic lupus erythematosus,folate biosynthesis,and proximal renal tubule bicarbonate recycling.Further parallel reaction monitoring validated 16 candidate proteins,of which 5 proteins-SERPINA1,APOA1,F2,PLG,and HRG-have not been reported to be associated with AKI but are related to acute phase responses and fibrinolysis.Conclusion: In this study,we established a new rat model of CI-AKI.Using this novel model,we found that iodixanol had lower nephrotoxicity than iohexol.Proteomic analysis identified metabolic pathways and 16 differentially expressed proteins associated with the development of CIAKI.The findings from this study help elucidate novel mechanisms underlying CI-AKI pathogenesis and provide theoretical and experimental foundations for preventing,diagnosing,and treating CI-AKI.