Date: Saturday, June 1, 2019
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: In kidney transplantation (KTx), despite recent advances of medical technology, chronic rejection accounts for 25% of the graft loss. Chronic active antibody-mediated rejection (CAAMR) is particularly a problem, but the progression remains unclear, and there is no effective treatment. Furthermore, current diagnosis relies on renal biopsy, which is invasive for patients. Therefore, it is urgently required to identify a biomarker.We previously found an excessive NFkB-activating mechanism in non-immune cells (inflammation amplifier: IA) is induced by the co-activation of NFkB and STATs, which is essential for several human diseases. Thus, this study aims to obtain new biomarkers for CAAMR, based on IA.
*Methods: RNA sequence was performed using human renal proximal tubule epithelial cells to find genes involved in IA of kidney. To examine the relationship with CAAMR, we used renal biopsy and urine samples from KTx patients. Based on the results of biopsy, KTx patients were divided into 4 groups (NED: normal, IF/TA: interstitial fibrosis and tubular atrophy, CNI: calcineurin inhibitors toxicity, and CAAMR), and examined together with healthy volunteers.
*Results: RNA sequence revealed that co-stimulation of IL6 and TNFα, which are inducers of IA, caused elevations of NFkB, STATs, and a gene called KIAM (Kidney IA Mediator). First, immunostaining showed that KIAM protein was expressed in renal tubule cells, and strongly observed in CAAMR group compared to NED. Second, to investigate the usefulness as a biomarker for CAAMR, KIAM protein was evaluated by western blotting analysis. It could not be detected with urine itself. Accordingly, we focused on exosomes which are known to be useful in the field of liquid biopsy. Interestingly, KIAM protein levels in a urinary exosomal fraction was higher in CAAMR significantly (Fig1). On the other hand, clinical laboratory data routinely used (eGFR, Proteinuria, N-acetyl-β-D-glucosaminidase: NAG) could not show significant differences.
*Conclusions: KIAM protein in urine exosomes, which are collected noninvasively, clearly expressed in CAAMR group, but not other groups. Moreover, there were no significant difference by the clinical data currently used for the diagnosis of CAAMR. Therefore, KIAM has the potential to become a novel non- invasive biomarker for early-stage CAAMR.
To cite this abstract in AMA style:Takada Y, Kamimura D, Higuchi H, Iwami D, Hotta K, Iwahara N, Shinohara N, Murakami M. Liquid Biopsy for Chronic Rejection after Kidney Transplantation. A Novel Non-Invasive Biomarker Involved in Inflammatory Amplifier [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/liquid-biopsy-for-chronic-rejection-after-kidney-transplantation-a-novel-non-invasive-biomarker-involved-in-inflammatory-amplifier/. Accessed January 16, 2021.
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