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Abstract: PO2044

A Peripheral Blood Transcriptomic Signature Predicts the Progression of Chronic Kidney Damage Post Transplant

Session Information

Category: Transplantation

  • 1901 Transplantation: Basic

Authors

  • Zhang, Weijia, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Yi, Zhengzi, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Wei, Chengguo, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Xi, Caixia, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Huang, Weiqing, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Sun, Zeguo, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Farouk, Samira S., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Cravedi, Paolo, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Menon, Madhav C., Yale University, New Haven, Connecticut, United States
  • Colvin, Robert B., Massachusetts General Hospital, Boston, Massachusetts, United States
  • O'Connell, Philip John, Westmead Institute for Medical Research, Westmead, New South Wales, Australia
  • Murphy, Barbara T., Icahn School of Medicine at Mount Sinai, New York, New York, United States
Background

Chronic kidney damage post-transplant is a major risk of allograft loss. The aim of this study was to identify a transcriptomic signature from peripheral blood collected at 3 months post-transplant to predict the progression of chronic kidney damage after transplant.

Methods

We inspected kidney functional and histologic changes from the baseline (pre-implantation) to 1 year post-transplant in 112 kidney transplant recipients from the prospective Genomics of Chronic Allograft Rejection (GoCAR) study and identified the patients who developed chronic kidney damage within 1 year (progressors). We then carried out RNA sequencing on the whole blood collected from these patients at 3 months post-transplant to identify a transcriptomic signature predictive of the progression of chronic kidney damage in the training set and validated by the testing set.

Results

Among 112 patients, we identified 30 progressors who developed kidney damage within 1 year post-transplant with a Chronic Allograft Damage Index (CADI) score increase by ≥ 2, and 55 non-progressors with a normal histology at both the baseline (CADI<2) and 12 months (CADI<=2) post transplant. The remaining 27 patients had a histological lesion at the baseline with a high CADI >=2 but no progression at 12 months. From the progressors and non-progressors (total n=85), we randomly selected 55 patients as a training set and the remaining 30 patients as a testing set. From the training set, we identified a 9-gene set that predicts kidney damage at 12 months with AUC=0.88 and validated the prediction model in the testing set with AUC=0.79, superior to the Kidney Donor Risk Index (KDRI) in the deceased-donor population. The 9-gene set performed moderately in the patients who received a kidney with an intermediate or severe pathological lesion (n=27, AUC=0.68).

Conclusion

We presented a useful blood transcriptomic signature to accurately risk-stratify the progression of chronic kidney damage post-transplant, especially for those patients who received a healthy kidney.

Funding

  • Other NIH Support