Donor-Derived Cell-Free DNA as a Non-Invasive Biomarker for Graft Rejection in Kidney Transplant Recipients: A Prospective Study among the Indian Population

供体来源的游离 DNA 作为肾移植受体移植排斥反应的非侵入性生物标志物:针对印度人群的前瞻性研究

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作者:Naveen Kumar, Archita Tandon, Rashmi Rana, Devinder Singh Rana, Anil Kumar Bhalla, Anurag Gupta, Mohinder Pal Sachdeva, Rohit Singh Huirem, Kirti Chauhan, M H Yashavarddhan, Atul Basnal, Ritu Gupta, Prashant Kumar Mallick, Nirmal Kumar Ganguly

Abstract

Monitoring graft health and detecting graft rejection is crucial for the success of post-transplantation outcomes. In Western countries, the use of donor-derived cell-free DNA (dd-cfDNA) has gained widespread recognition as a diagnostic tool for kidney transplant recipients. However, the role of dd-cfDNA among the Indian population remains unexplored. The recipients were categorized into two groups: the post-transplant recipient (PTR) group (n = 16) and the random recipient (RR) group (n = 87). Blood samples were collected daily from the PTR group over a 7-day period, whereas the RR group's samples were obtained at varying intervals. In this study, we used a targeted approach to identify dd-cfDNA, which eliminated the need for genotyping, and is based on the minor allele frequency of SNP assays. In the PTR group, elevated dd-cfDNA% levels were observed immediately after transplantation, but returned to normal levels within five days. Within the RR group, heightened serum creatinine levels were directly proportional to increased dd-cfDNA%. Sixteen recipients were advised to undergo biopsy due to elevated serum creatinine and other pathological markers. Among these sixteen recipients, six experienced antibody-mediated rejection (ABMR), two exhibited graft dysfunctions, two had active graft injury, and six (37.5%) recipients showed no rejection (NR). In cases of biopsy-proven ABMR and NR, recipients displayed a mean ± SD dd-cfDNA% of 2.80 ± 1.77 and 0.30 ± 0.35, respectively. This study found that the selected SNP assays exhibit a high proficiency in identifying donor DNA. This study also supports the use of dd-cfDNA as a routine diagnostic test for kidney transplant recipients, along with biopsies and serum creatinine, to attain better graft monitoring.

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