The use of plasma donor-derived, cell-free DNA to monitor acute rejection after kidney transplantation

Abstract

Background After transplantation, cell-free deoxyribonucleic acid (DNA) derived from the donor organ (ddcfDNA) can be detected in the recipient’s circulation. We aimed to investigate the role of plasma ddcfDNA as biomarker for acute kidney rejection. Methods From 107 kidney transplant recipients, plasma samples were collected longitudinally after transplantation (Day 1 to 3 months) within a multicentre set-up. Cell-free DNA from the donor was quantified in plasma as a fraction of the total cell-free DNA by next generation sequencing using a targeted, multiplex polymerase chain reaction-based method for the analysis of single nucleotide polymorphisms. Results Increases of the ddcfDNA% above a threshold value of 0.88% were significantly associated with the occurrence of episodes of acute rejection (P = 0.017), acute tubular necrosis (P = 0.011) and acute pyelonephritis (P = 0.032). A receiver operating characteristic curve analysis revealed an equal area under the curve of the ddcfDNA% and serum creatinine of 0.64 for the diagnosis of acute rejection. Conclusions Although increases in plasma ddcfDNA% are associated with graft injury, plasma ddcfDNA does not outperform the diagnostic capacity of the serum creatinine in the diagnosis of acute rejection.

Diagnostic Performance of Donor-Derived Plasma Cell-Free DNA Fraction for Antibody-Mediated Rejection in Post Renal Transplant Recipients: A Prospective Observational Study

“…At a threshold 52 cp/mL, it had a sensitivity of 73%, a specificity of 73%, a PPV of 13%, and an NPV of 98%. They believed that cfDNA fraction was subject to influences by recipient cfDNA levels which tended to increase during (27) presented the contradictory results and they found that plasma ddcfDNA did not outperform the diagnostic capacity of the serum creatinine in the diagnosis of acute rejection. Our study and three other studies all showed that cfDNA fraction has a high NPV for ABMR diagnosis, which means most of patients with negative cfDNA fraction (below the threshold) do not have ABMR, suggesting that donor-derived cfDNA fraction measurement may avoid unnecessary kidney transplant needle biopsy when the other types of allograft injury can be excluded, especially in patients on anticoagulation medication or patients for whom it is inconvenient to perform kidney needle biopsy.…”

Urine Donor–Derived Cell-Free DNA Helps Discriminate BK Polyomavirus-Associated Nephropathy in Kidney Transplant Recipients With BK Polyomavirus Infection

“…Studies have shown that measuring plasma dd-cfDNA is useful for the detection of allograft rejection/injury episodes in organ transplant recipients (3,20). However, elevated dd-cfDNA isn't specific for rejection; elevated levels are also observed in BKPyVAN in sporadic reports (4,9,10). This large-scale clinical study systematically assessed the performance of urine dd-cfDNA and dd-cfDNA% for discriminating BKPyVAN in adult kidney transplant recipients with BKPyV viruria.…”

“…Whitlam et al reports the plasma dd-cfDNA% was 1.5% in one patient with BKPyVAN (9). However, another study finds that plasma dd-cfDNA% remained below the threshold value (0.88%) in three cases of BKPyVAN (10). The majority of research on the use of dd-cfDNA for diagnosing acute rejection/injury has been focused on the proportion of dd-cfDNA in plasma.…”

The urinary microbiome shows different bacterial genera in renal transplant recipients and non-transplant patients at time of acute kidney injury – a pilot study

“…Kidney transplant recipients have an elevated AKI risk, which may result in graft loss [36,37]. Urinary tract infections are the most prevalent infectious complication in RTX patients and play a major cause in the development of AKI [1].…”