Non-invasive diagnosis for acute rejection using blood mRNA signature reflecting allograft status in kidney transplantation
- Affiliations
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- 1Department of Internal Medicine-Nephrology, Kyung Hee University Hospital at Gangdong, Seoul, Korea
- 2Department of Core Research Laboratory, Medical Science Institute, Kyung Hee University Hospital at Gangdong, Seoul, Korea
Abstract
- Background
Despite improvements in immunosuppressive therapy over the years, acute rejection (AR) episodes that required treatment are still a significant risk factor for poor graft outcomes. Monitoring renal graft status through peripheral blood (PB) rather than invasive biopsy could reduce bleeding risk and costs.
Methods
Blood gene biomarker panels were discovered by microarrays and subsequently validated and cross-validated by qPCR. A total of 112 human PB samples, each paired with a graft biopsy, were analyzed (58 AR, 42 stable, and 12 other causes of graft injury). The differentially expressed genes by microarray, Q-PCR analysis of a four gene-set (GRB10, LGALS3BP, OLR1, and RNASE2) classified AR.
Results
We developed AR prediction model with the blood mRNAs by a binary logistic regression, and the AUC of the model was 0.76 in the training set. In addition, the decision curve analysis indicated a range of reasonable threshold probabilities for biopsy.
Conclusions
Therefore, we suggest blood mRNA signature may serve as a non-invasive monitoring tool of AR for a clinical application and can assist with deciding whether to perform a biopsy in a recipient with a rise in creatinine and probably justifies a biopsy.