Donor-Derived Cell-Free DNA in Kidney Transplantation as a Potential Rejection Biomarker: A Systematic Literature Review

Abstract

Kidney transplantation (KTx) is the best treatment method for end-stage kidney disease. KTx improves the patient’s quality of life and prolongs their survival time; however, not all patients benefit fully from the transplantation procedure. For some patients, a problem is the premature loss of graft function due to immunological or non-immunological factors. Circulating cell-free DNA (cfDNA) is degraded deoxyribonucleic acid fragments that are released into the blood and other body fluids. Donor-derived cell-free DNA (dd-cfDNA) is cfDNA that is exogenous to the patient and comes from a transplanted organ. As opposed to an invasive biopsy, dd-cfDNA can be detected by a non-invasive analysis of a sample. The increase in dd-cfDNA concentration occurs even before the creatinine level starts rising, which may enable early diagnosis of transplant injury and adequate treatment to avoid premature graft loss. In this paper, we summarise the latest promising results related to cfDNA in transplant patients.

Current Trends in Cell-Free DNA Applications. Scoping Review of Clinical Trials

“…Similarly, in oncology, minimally invasive diagnostics might potentially replace traditional tissue biopsies. Furthermore, similarly to cancer, it requires highly sensitive detection methods which will be able to detect less than 1% of DNA from the total cfDNA fraction [29].…”

Clinical outcomes from the Assessing Donor-derived cell-free DNA Monitoring Insights of kidney Allografts with Longitudinal surveillance (ADMIRAL) study

“…In the absence of clinical signs, clinicians seeking to identify subclinical allograft injury and intervene prior to development of irreversible damage, were forced to rely on invasive allograft biopsies, which have inherent limitations from sampling error and variation in interpretation. 1 Routine monitoring with donor-derived cell-free DNA (dd-cfDNA) after solid organ transplantation has been shown to accurately identify and characterize allograft injury, [1][2][3] correlate with pathologic findings, [4][5][6] and assess response to therapy including treatment of rejection. 7,8 Importantly, evaluation in dd-cfDNA have been demonstrated to occur ahead of clinically apparent organ injury.…”

The Application of Nanoparticles in Diagnosis and Treatment of Kidney Diseases

“…After organ transplantation, the main clinical problem is rejection, which requires lifelong immunosuppression, accompanied by susceptibility to infections and cancer. One of our works describes the potential use of cell-free DNA in monitoring patients after transplantation [ 134 ]. There is also a necessity for proper qualification of donors and prediction of graft function after kidney transplantation (KTx).…”

“…A limitation of DUS is the lack of possibility to monitor perfusion in the critical early post-transplantation period, and NIRS measures only tissue oxygenation [ 151 , 152 , 153 ]. Non-invasive methods of monitoring early graft function include measuring of serum donor-derived, cell-free DNA, whose potential applications have been described [ 134 ]. Non-invasive methods of monitoring are still investigated by many researchers [ 154 ].…”