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Abstract: SA-PO587

Severity and Frequency of Tubule Injury Induced by Ischemia-Reperfusion Determines Prognosis of AKI

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Dong, Yang, Shanghai 6th People's Hospital affiliated to Shanghai Jiaotong University, Shanghai, China
  • Fan, Ying, Shanghai 6th People's Hospital affiliated to Shanghai Jiaotong University, Shanghai, China
  • Zhang, Qunzi, Shanghai 6th People's Hospital affiliated to Shanghai Jiaotong University, Shanghai, China
  • Wen, Jiejun, Shanghai 6th People's Hospital affiliated to Shanghai Jiaotong University, Shanghai, China
  • Wang, Yiyun, Shanghai 6th People's Hospital affiliated to Shanghai Jiaotong University, Shanghai, China
  • Wang, Niansong, Shanghai 6th People's Hospital affiliated to Shanghai Jiaotong University, Shanghai, China
Background

Ischemia is a common etiology in human acute kidney injury (AKI), which is an underestimated, yet significant predisposing factor for development of chronic kidney disease (CKD). However, a systematic and explicit reference standard is lacking for researchers when IRI models with divergent outcomes are to establish. Also, the biomarkers reflecting AKI to CKD progression are particularly lacking. The purpose of the current study was to establish suitable mice models simulating different clinical situations of renal ischemia patients, investigating the time and frequency effect of ischemia on AKI and subsequent AKI to CKD progression and exploring the potential function of noninvasive biomarkers KIM-1 and NGAL in predicting the renal outcome and prognosis.

Methods

Male C57BL/6J mice were subjected to different durations and episodes of ischemia attack for the UIRI (Unilateral Ischemia-Reperfusion Injury). We collected and analyzed the kidney samples at different time point post-ischemia. The concomitant changes of tubular injury biomarkers KIM-1 and NGAL in blood and urine along with different disease progression pattern were also investigated.

Results

We found that short-term duration of ischemia induced mild and reversible AKI in mice, while long-term duration of ischemia led to severe and progressive AKI. Repeated attack of moderate ischemia reperfusion injury could be applied to establish a model of AKI on CKD in mice. Furthermore, levels of KIM-1 and NGAL restored completely in reversible AKI, while they remained increased in progressive AKI. To be specific, levels of NGAL presented an increasing tendency till the chronic phase of the disease , while levels of KIM-1 merely peaked at the acute phase then suffered a subsequent decrease although still significantly higher than basal values.

Conclusion

In conclusion, different severity and frequency of ischemia injury dictate the divergent outcomes of ischemia-induced AKI. Both KIM-1 and NGAL enable noninvasive and early detection of AKI, also NGAL may better reflecting and predicting the process of AKI to CKD progression.

Funding

  • Government Support - Non-U.S.