cfDNA Analysis: Comparison
Please note this is a comparison between Version 2 by Camila Xu and Version 1 by Isabel Legaz.

Degraded DNA fragments released into the blood or other fluids are known as cfDNA. Its first detection dates back to 1948 in patients with systemic lupus erythematosus.

  • donor-derived cell-free DNA (cfDNA)
  • graft injury
  • acute rejection
  • organ transplant

1. Introduction

In kidney transplantation, a biopsy is currently the gold standard for monitoring the transplanted organ. A biopsy involves taking a small tissue sample from the transplanted kidney, which is then examined under a microscope to assess organ health. This is done to assess for any signs of rejection or other problems that may be occurring in the transplanted kidney. However, this is far from an ideal screening method given its invasive nature and the discomfort it can cause the patient. Large-scale studies in renal transplantation show that approximately 1% of biopsies generate major complications, with a risk of macroscopic hematuria greater than 3.5% [1]. Most biopsy-related complications, such as pain and bleeding, are minor and localized, and can be managed conservatively [2]. The most severe complication, however, is the risk of perforation of the collecting system or the kidney itself, which can result in severe hemorrhage, sepsis, and even death. To minimize the risk of complications, careful patient selection, proper imaging guidance, and specialized instruments and techniques are essential [3,4][3][4]. Imaging techniques, such as ultrasound and computed tomography (CT), are essential for accurate needle placement. Ultrasound imaging is the most commonly used modality for needle guidance due to its versatility, cost-effectiveness, and relative safety. It allows for real-time visualization of the renal transplant and the surrounding anatomy, making it ideal for guiding percutaneous needle placement. CT imaging can also be used but is typically reserved for more complex cases with insufficient ultrasound imaging.
In addition, with current immunosuppressive therapies, the detection of subclinical rejection is too infrequent to justify this risk, which has meant that many units no longer perform these routine biopsies [5], thus raising the urgent need to find a new non-invasive biomarker that allows the detection of said rejection in order to intervene in time or modify immunosuppression. In response to this need, recent studies have shown that non-invasive biomarkers could be a viable option for detecting subclinical rejection [6,7,8,9][6][7][8][9]. These non-invasive biomarkers include urinary and serum markers such as urinary albumin-to-creatinine ratio (UACR) and donor-specific antibodies (DSA). Additionally, imaging techniques, such as magnetic resonance imaging (MRI) and ultrasound (US), have been used to detect graft changes that may signal rejection [10,11,12][10][11][12]. Finally, genetic and epigenetic biomarkers, such as microRNAs, have also been used to detect subclinical rejection [13,14,15][13][14][15]. Ultimately, using these non-invasive biomarkers could help identify and intervene in cases of subclinical rejection earlier, thus avoiding more serious complications.

2. Types de Cell-Free DNA

Degraded DNA fragments released into the blood or other fluids are known as cfDNA. Its first detection dates back to 1948 in patients with systemic lupus erythematosus [20][16]. It would not be until 1970 that this new biomarker would begin to be considered helpful for the clinic, as researchers observed differences in its concentration depending on the health status of the individual studied and began to see its application in cancer patients by allowing the detection of fragments of tumor DNA in the blood [21][17]. Its interest increased when it was discovered that tumor cells not only released cfDNA into the bloodstream but that these fragments also had the genetic and epigenetic changes of the tumor cells from which they had originated [22][18]. Shortly after, analysis of fetal cfDNA in maternal plasma began to be used to detect Rh mismatches and chromosomal aneuploidies [23][19]. Recent literature shows that different cfDNA types can be used as biomarkers of various disease states [16,24][20][21]. The following stand out for their relevance: ccf mtDNA (circulating cell-free mitochondrial DNA), ctDNA (circulating tumor DNA), cffDNA (cell-free fetal DNA), and dd-cfDNA (donor-derived cell-free DNA). These types and their applications are listed in Table 1.
Table 1.
Different types of cfDNA and their main clinical applications.


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