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Abstract: SA-PO060

Identification of Very Early Response Genes and Sex-Dependent Response Genes for Ischemia-Reperfusion Injury in Human Transplant Patients

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Lee, Nathan, Brigham and Women''s Hospital, Boston, Massachusetts, United States
  • Olauson, Hannes, Brigham and Women''s Hospital, Boston, United States
  • Cheng, Shun-Yang, Brigham and Women''s Hospital, Boston, Massachusetts, United States
  • Choi, Kyung hwa, Brigham and Women''s Hospital, Boston, United States
  • Zeleznik ramuta, Taja, Brigham and Women''s Hospital, Boston, United States
  • Bonventre, Joseph V., Brigham and Women's Hospital, Boston, Massachusetts, United States
Background

Ischemia-reperfusion injury (IRI) is highly implicated in various kidney conditions leading to acute (AKI) and chronic kidney disease (CKD). IRI during renal transplantation often initiates responses that can result in poor outcome and the loss of kidney graft viability. It is important to identify very early response programs that can be utilized to better characterize the pathobiology and identify therapeutic targets to minimize the injury. Furthermore, it has been shown that sex influences susceptibility to kidney IRI. However, such early response programs for IRI and sex-dependent response programs are poorly understood with most of our knowledge derived from animal studies or tissue analyses after longer times post-ischemia in the transplant population.

Methods

Twenty paired biopsies from the cortical region of the human kidney were obtained before and after ischemia-reperfusion during living donor transplantation, with minimal cold ischemia time (1-2 hours) compared to other studies. Glomeruli were removed and the tubulointerstitial fraction was subjected to RNA sequencing (RNA-seq). Genes were identified that were differentially regulated early in response to IRI.

Results

There was a robust and novel early response program to IRI. When compared to published datasets of both human and rodents, there was a significant overlap of the post-ischemic transcriptional profiles. Interestingly, however, our results identified a unique set of highly upregulated early response genes that have not been identified previously for their roles in kidney IRI. Furthermore, we identified sex-dependent genes that were differentially upregulated in males and females.

Conclusion

Within 1-2 hr of cold ischemic time in transplanted human kidneys there is a unique set of genes which reflect a very early response. There was a different early response to IRI between males and females. Findings from this study can be utilized to further investigate mechanisms and potential therapeutic options for IRI and AKI.

Funding

  • NIDDK Support