The Study Of Indicators And Affecting Factors In The Prognosis Of AKI Induced By Ischemia Reperfusion

BackgroundAcute kidney injury(AKI)is a common clinical syndrome.Previously considered to be a benign and reversible syndrome,AKI is now associated with the progression of chronic kidney disease(CKD)and end-stage renal disease(ESRD).Ischemia reperfusion injury(IRI)is one of the most common causes of AKI,however,the pathogenesis and biomarkers predicting the progression of IRI-induced AKI to CKD still remain unclear.ObjectivesWe propose to systematically summarize the characteristics of different IRI models with different ischemic duration and episodes,and to follow up on the dynamic changes of the two classic and recognized renal injury markers KIM-1 and NGAL.We hope to provide a better understanding of these I/R models and their relevance to human AKI,and to help researchers and clinicians better monitor AKI progression.MethodsA side-by-side comparison between different IRI animal models with variable ischemic duration and episodes was performed.The inflammatory reaction,the status of cellular apoptosis and proliferation,as well as the presence of fibrogenesis in IRI mice with different renal prognosis were detected.And the dynamic changes of KIM-1 and NGAL continuously from AKI to CKD phases were studied as well.Results 1.Short-term duration of ischemia induced mild renal tubule-interstitial injury which was completely reversed at acute phase of kidney injury,while long-term duration of ischemia caused severe tubular damage,cell apoptosis and inflammatory infiltration at early disease stage,leading to permanent chronic kidney fibrosis at the late stage.2.Apoptosis and inflammatory response were mild in reversible AKI model,and the proliferation response of renal tubular epithelial cells was prominent.In AKI-to-CKD progression model,however,apoptosis and inflammatory response were severe and persistent,with interstitial fibrogenesis seen clearly.3.We established the Repeated Kidney IRI-attack Model successfully,through which we found that repeated attacks of IRI accelerated the progression of AKI to CKD.4.The apoptosis and inflammatory status,as well as the proliferation of tubular interstitial fibroblasts were aggravated in repeat IRI attack models,which may all contribute to the acceleration of the disease progression.5.Both serum and urine levels of KIM-1 and NGAL enable the noninvasive and early detection of AKI,as well as the evaluation of AKI severity.However,NGAL may better reflect the progression of AKI to CKD.Conclusion In conclusion,in the current study,we established UIRI mouse models to mimic diverse clinical outcomes of ischemia-induced kidney injury in AKI patients: reversible AKI,AKI-to-CKD progression and recurrent AKI.We carefully assessed how the severity and frequency of ischemia injury determined the progression and outcome of ischemia-induced AKI.Inflammation,cell apoptosis and fibrogenesis are likely the underlying mechanisms contributing to the AKI-to-CKD transition.Both serum and urine levels of KIM-1 and NGAL enable the noninvasive and early detection of AKI.However,NGAL better reflect AKI-to-CKD transition.We believe that our study is the first to perform a detailed side-by-side comparison of different IRI animal models with variable ischemia durations and frequencies.Our findings will be helpful for scientists to select an adequate IRI model for studying different pathological processes related to AKI.We also believe that our study is the first to provide a temporal profile of KIM-1 and NGAL from the acute phase to the chronic phase in an IRI mouse model,which may help researchers and clinicians better monitor AKI progression.