Impact of Ultrasound-guided Percutaneous Core Needle Biopsy on Biomarkers of Human Kidney Allograft Status

BACKGROUND: Deciphering the impact of invasive percutaneous core needle biopsy of the kidney allograft on diagnostic biomarkers may help guide their clinical usage. METHODS: We prospectively enrolled 39 adult kidney allograft recipients (patients) who underwent 41 clinically indicated, ultrasound-guided, percutaneous core needle biopsies. Pre- and post-biopsy urines were analyzed for urinary cell 3-gene signature score (UroMap), and the bloods for peripheral blood gene expression score (AlloMap Kidney) and plasma donor-derived cell-free DNA percentage (dd-cfDNA). We performed statistical analyses to compare pre- and post-biopsy values. RESULTS: Median A260/A280 ratios of RNA from pre- and post-biopsy urines were 1.99 and 2.01, respectively; RNA yield, 0.78 versus 0.76 micrograms; and transcript copies of 18S rRNA, TGFβ1, CD3ε, CXCL10, and UroMap score were similar (all P > 0.05, Wilcoxon matched-pairs signed-rank test). The pre- and post-scores were very strongly correlated (Spearman's correlation coefficient [r s ]: 0.83, P < 0.0001). AlloMap Kidney scores in pre- and post-biopsy peripheral blood were similar ( P > 0.05) and strongly correlated (r s = 0.70, P < 0.0001). dd-cfDNA in post-biopsy plasma was higher than in pre-biopsy plasma (0.61% versus 0.26%, P = 0.004). The higher post-biopsy percentage was replicated in an independent cohort of 119 post-biopsy plasma collected from 105 patients with no rejection biopsies. To normalize the biopsy-associated increase, a correction factor of -0.36% was derived by subtracting the pre-biopsy dd-cfDNA percent from the post-biopsy percent. CONCLUSIONS: UroMap and AlloMap Kidney scores are not affected by the biopsy procedure. However, dd-cfDNA increases following the biopsy procedure and could be normalized using the correction factor identified in this study.