Abstract
Patient monitoring after kidney transplantation (KT) for early detection of allograft rejection remains key in preventing allograft loss. Serum creatinine has poor predictive value to detect ongoing active rejection as its increase is not sensitive, nor specific for acute renal allograft rejection. Diagnosis of acute rejection requires allograft biopsy and histological assessment, which can be logistically challenging in some cases and carries inherent risk for complications related to procedure. Donor-derived cell-free DNA (dd-cfDNA), DNA of donor origin in the blood of KT recipient arising from cells undergoing injury and death, has been examined as a potential surrogate marker for allograft rejection. A rise in dd-cfDNA levels precedes changes in serum creatinine allows early detections and use as a screening tool for allograft rejection. In addition, when used in conjunction with donor-specific antibodies (DSA), it increases the pre-biopsy probability of antibody-mediated rejection (ABMR) aiding the decision-making process. Advancements in noninvasive biomarker assays such as dd-cfDNA may offer the opportunity to improve and expand the spectrum of available diagnostic tools to monitor and detect risk for rejection and positively impact outcomes for KT recipients. In this this article, we discussed the evolution of dd-cfDNA assays and recent evidence of assessment of allograft rejection and injury status of KT by the use of dd-cfDNA.
Highlights
Kidney Transplantation (KT) is the best treatment option for patients with end-stage kidney disease (ESKD) [1]
An emerging area of research has been the advent of assays that detect donor-derived cell-free DNA [14,23,43]. dd-cfDNA, DNA of donor origin in the blood of the KT recipient, has developed as a noninvasive marker suggestive of allograft rejection, since it originates from cells undergoing injury and death, and can be found in serum, plasma, urine, saliva, feces, synovial fluid, CSF, and peritoneal fluid. cfDNA technology has been utilized in prenatal testing and oncology, and research for the past decade has led to the application and development of this technology for evaluation of allograft rejection [44,45]
The findings of this study suggested that dd-cfDNA can be utilized to evaluate renal allograft status in repeat transplant recipients
Summary
Kidney Transplantation (KT) is the best treatment option for patients with end-stage kidney disease (ESKD) [1]. The development of novel technologies (Table 1) applied to the monitoring of acute allograft rejection include genomics, transcriptomics, proteomics, and metabolomics, which quantify the abundance of circulating cell free DNA, gene transcripts (mRNA), proteins, and metabolites, respectively, in cell/tissue extracts or biofluids [14,15,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42] These technologies have advanced the non-invasive diagnosis of acute rejection among KT patients and allow early identification of allograft injury and timely intervention.
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