Korean J Transplant.  2022 Nov;36(Supple 1):S219. 10.4285/ATW2022.F-3567.

Prospective study to evaluate the effectiveness of donor-derived cell-free DNA for early diagnosis of biopsy-proven rejection in renal transplant recipients

• Kim HD
• Bae H
• Eum SH
• Lee H
• Ko EJ
• Yang CW
• Chung BH
• Oh EJ

• KMID: 2535284
• DOI: http://doi.org/10.4285/ATW2022.F-3567

Abstract

Background
In this study, we investigated to verify whether the titer of donor-derived cell-free DNA (dd-cfDNA) has diagnostic value in predicting biopsy-proven rejection in kidney transplant recipients (KTR).
Methods
This study was prospectively designed to verify the effectiveness of dd-cfDNA for the diagnosis of biopsy-proven rejection in KTR. Analysis was performed on 42 KTR in Seoul St. Mary's Hospital. All these patients underwent an indication bi-opsy for reasons such as elevated serum creatinine, proteinuria, and DSA detection. Blood samples were collected immediately before the biopsy and dd-cfDNA test was performed using the AlloSeq cfDNA kit. The biopsy specimen was diagnosed by a renal pathologist according to Banff classification.
Results
Of the total 42 patients, 12 patients were diagnosed with rejection, and the other 30 patients were diagnosed with glomerulonephritis, diabetic nephropathy, acute tubular necrosis, and BK virus nephropathy. The mean titer of dd-cfDNA in patients diagnosed with rejection was 1.38%, which was higher than 0.61% of patients without rejection (P=0.013). The median dd-cfDNA in all patients was 0.425%. Patients with dd-cfDNA values higher than the median value were assigned to the high dd-cfDNA group, and other patients were assigned to the low dd-cfDNA group. As a result of comparing the pathologic findings between two groups, the glomerulitis and peritubular capillaritis scores were higher in the high dd-cfDNA group. Chronic glomerulitis score was also higher in the high dd-cfDNA group but was not statistically significant (P=0.079). To evaluate the predictive value of cfDNA for rejection, receiver operating characteristic area under the curve revealed 0.74; 95% confidence in-terval, 0.58 to 0.91. Sensitivity and specificity for biopsy proven rejection at a cut-off of 0.39% dd-cfDNA were 91.7% and 63.3%, respectively.
Conclusions
In KTR, the dd-cfDNA is useful marker for allograft rejection. In particular, the predictive power of renal injury related to glomerulitis and peritubular capillaritis was high.