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Abstract: TH-PO1105

Predicting Transplant Rejection by a Composite Urinary Injury Score

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Yang, Joshua Young Cynming, University of California San Francisco, San Francisco, California, United States
  • Sarwal, Reuben Dev, University of California, San Francisco, Portola Valley, California, United States
  • Sigdel, Tara, University of California San Francisco, San Francisco, California, United States
  • Sarwal, Minnie, University of California San Francisco, San Francisco, California, United States
Background

While sequencing or PCR have been used for quantifying donor-derived cell-free DNA in plasma to detect allograft rejection, they remain expensive and inconvenient for patients and physicians. We assessed the performance of a novel urinary assay measuring nucleic acid, protein, and metabolic markers to provide a quantitative composite risk score without sequencing or PCR to detect kidney transplant (KT) rejection.

Methods

206 urine samples from 95 KT patients were collected and categorized as stable (n = 157) or acute rejection (AR, n = 49). Samples were processed for quantification of urinary cfDNA and 5 additional protein markers using a custom microwell-based assay, to develop a translant rejection score. The score from longitudinally collected samples (n = 47) from 8 KT patients who were stable and had no evidence of subclinical rejection was correlated with days post-transplant to generate a 95% prediction curve which was used to generate a normalized rejection score for all samples.

Results

The urinary rejection score is significantly increased immediately post-transplant and decreases to a steady baseline by 3 months post-transplant (Figure 1A). The median level of 95% prediction interval-normalized rejection score was significantly higher in AR as compared with stable samples (0.64 vs. -0.71, P < 0.0001) (Figure 1B). The urinary rejection score showed high performance in discriminating the stable and AR samples, with an AUC of 0.9649 (P < 0.0001). At a threshold set at a normalized value of 0, the sensitivity and specificity of the assay was 93.88% and 94.90% respectively (Figure 1C), suggesting that the assay could be used to screen patients at risk of rejection to avoid unnecessary biopsies in the clinical setting.

Conclusion

This novel urinary rejection score enables rapid and accurate discrimination of AR from stable patients without the costs associated with sequencing. As collection of urine requires no training and can be performed as often as needed, this assay can provide inexpensive, accurate, and longitudinal assessment of AR in KT patients.

Figure 1. Determination of rejection score kinetics post-transplantation and discrimination of AR.

Funding

  • NIDDK Support