{"id":1956,"date":"2022-06-28T16:30:37","date_gmt":"2022-06-28T08:30:37","guid":{"rendered":"https:\/\/transnovo.com\/news\/gcfdna%e5%8a%a8%e6%80%81%e7%9b%91%e6%b5%8b%e5%9c%a8%e8%82%be%e7%a7%bb%e6%a4%8d%e6%9c%af%e5%90%8e%e7%9a%84%e9%87%8d%e8%a6%81%e5%ba%94%e7%94%a8%e4%bb%b7%e5%80%bc\/"},"modified":"2022-06-28T16:30:37","modified_gmt":"2022-06-28T08:30:37","slug":"gcfdna%e5%8a%a8%e6%80%81%e7%9b%91%e6%b5%8b%e5%9c%a8%e8%82%be%e7%a7%bb%e6%a4%8d%e6%9c%af%e5%90%8e%e7%9a%84%e9%87%8d%e8%a6%81%e5%ba%94%e7%94%a8%e4%bb%b7%e5%80%bc","status":"publish","type":"post","link":"https:\/\/transnovo.com\/en\/news\/gcfdna%e5%8a%a8%e6%80%81%e7%9b%91%e6%b5%8b%e5%9c%a8%e8%82%be%e7%a7%bb%e6%a4%8d%e6%9c%af%e5%90%8e%e7%9a%84%e9%87%8d%e8%a6%81%e5%ba%94%e7%94%a8%e4%bb%b7%e5%80%bc\/","title":{"rendered":"The important value of GcfDNA dynamic monitoring after renal transplantation"},"content":{"rendered":"
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Preface<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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With the great progress in renal transplantation, post-transplantation complications and immunosuppressive drug adjustments can affect graft function and survival, and dynamic post-transplantation monitoring has received increasing attention. Graft monitoring has traditionally relied on serum creatinine and kidney biopsy.<\/p>\n


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However, serum creatinine testing is more delayed, lacks sensitivity, and cannot detect early kidney injury. Kidney biopsy is not suitable for frequent monitoring because of the risk of invasiveness and bleeding.<\/p>\n


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Donor-derived free DNA (GcfDNA, also known clinically as dd-cfDNA) is a non-invasive assay that<\/span><\/strong>It is a new and promising dynamic test method after kidney transplantation, which can assess the rejection and injury status of the graft more frequently, quantitatively and safely, and can detect kidney injury early.1<\/sup>.<\/p>\n<\/section>\n<\/section>\n<\/section>\n


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ADMIRAL is a large, multicenter, observational cohort study that included 1092 adult kidney transplant patients from 7 centers and analyzed dynamic data on dd-cfDNA from June 2016 to January 2020 to assess the correlation with allogeneic rejection2<\/sup>.<\/p>\n


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Of which for 203<\/span>Patients<\/span>Took 2<\/span>19 biopsy specimens and simultaneous blood<\/span>GcfDNA test.<\/span>The results of the study showed that the median dd-cfDNA level of 0.231 TP3T in patients with no rejection by biopsy was significantly lower than the median dd-cfDNA level of 1.61 TP3T in patients with cellular or humoral rejection by biopsy (P < 0.0001). However, there was no statistically significant difference in median creatinine between patients with biopsies showing no rejection and patients with Banff-defined rejection (1.38 mg\/dL vs 1.57 mg\/dL; P = 0.096). The AUC for dd-cfDNA in patients with differential rejection was 0.798, which was significantly higher than the AUC for creatinine of 0.492 (P < 0.001) (Figure 1).<\/p>\n


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Regarding the relationship between dd-cfDNA and renal function, the study found no significant trend of association due to the unstable eGFR in the first 4 months after transplantation. In contrast, analysis of dynamic renal function monitoring between months 12 and 36 showed a significant correlation between elevated dd-cfDNA and subsequent decline in renal function (Spearman correlation coefficient R: -0.84; P=0.01) (Figure 2).<\/p>\n


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Elevated dd-cfDNA (\u22650.5%) was significantly associated with decreased eGFR 3 years after transplantation, and persistent elevation of dd-cfDNA (\u22650.5%) doubled the risk of decreased eGFR by 25% (HR: 1.97; P=0.041).<\/p>\n


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In addition, dd-cfDNA > 0.5% was associated with a nearly 3-fold increase in the risk of de novo donor-specific antibodies (dnDSA) (HR: 2.71; P=0.001) (Figure 3). In multivariate analysis, every 1% increase in dd-cfDNA levels was associated with a 20% increase in dnDSA risk (HR: 1.19; P=0.004).Studies have shown that dd-cfDNA can be used for long-term dynamic monitoring of graft function, early detection of graft injury and rejection.<\/span><\/strong><\/p>\n


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Figure 1. dd-cfDNA and creatinine levels in patients with\/without rejection<\/p>\n<\/section>\n


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Figure 2. eGFR in relation to dd-cfDNA in patients up to 36 months after transplantation<\/p>\n<\/section>\n


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Figure 3. relationship between dd-cfDNA and dnDSA<\/p>\n<\/section>\n


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dd-cfDNA allows long-term dynamic monitoring of post-operative graft rejection, renal function and renal injury, as well as other factors that are detrimental to graft survival, including post-operative complications, drug toxicity, opportunistic infections, and recurrence of primary disease.<\/p>\n


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The first month after renal transplantation is dominated by postoperative healing, early immune rejection of the graft, and postoperative complications. dd-cfDNA helps to establish the baseline level of patients after surgery, detect early postoperative complications, and acute rejection.<\/p>\n


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The dose of immunosuppressive drugs is usually adjusted in the 2nd month and dd-cfDNA helps to assess changes after the adjustment of immunosuppressive drugs and can identify early rejection reactions.<\/p>\n


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Month 3 immunosuppressive drug tapering was associated with an increased risk of subsequent acute rejection, and dd-cfDNA helped to detect renal injury and stratify risk in adventitial patients.<\/p>\n


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The risk of rejection increases in month 4 as patients switch from induction therapy to oral therapy alone, which is an important time point for dd-cfDNA assessment of renal injury.<\/p>\n


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Antibody-mediated rejection (AMR) at months 6 and 9 is considered a major cause of late graft failure, and dnDSA correlates with both acute and chronic AMR. dd-cfDNA helps to identify the association of dd-cfDNA with dnDSA and patients at risk of developing dnDSA or graft injury.<\/p>\n


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Month 12 is accompanied by a new round of laboratory testing and clinical evaluation, and dd-cfDNA helps detect subclinical molecular impairment in serum creatinine insensitivity and provides further risk stratification that can help predict the long-term prognosis of patients.<\/p>\n


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Quarterly ambulatory blood monitoring is recommended from year 2 onwards to monitor changes in graft function, levels of immunosuppression and to determine if drug toxicity and rejection are occurring, providing clinicians with an accurate, sensitive, non-invasive biomarker of allograft injury when dd-cfDNA is increased, helping to identify rejection early3<\/sup>.<\/p>\n


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Summary<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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<\/svg><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n
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GcfDNA dynamic monitoring has important application value after renal transplantation, which can dynamically, quantitatively and non-invasively assess the rejection, renal function and renal injury of the graft after transplantation and dynamic adjustment of drugs. Considering the economic factors, we suggest that for stable postoperative patients, it can be tested at 1 month and 3 months postoperatively to establish the baseline level, and for high-risk patients, we suggest 1 month, 3 months, 6 months, 9 months, and subsequent dynamic monitoring according to quarters to achieve early detection, early diagnosis, and early treatment to avoid premature loss of function of the transplanted kidney.<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Reference:
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1. Sam Kant et al. Donor-Derived Cell-Free DNA in Kidney Transplantation: Origins, Present and a Look to the Future . Medicina (Kaunas) . 2021;57(5):482.<\/span><\/p>\n

2. Lihong Bu,et al. Kidney Int .Clinical outcomes from the Assessing Donor-derived cell-free DNA Monitoring Insights of kidney Allografts with Longitudinal surveillance (ADMIRAL) study . 2022 ;101(4):793-803.<\/span><\/p>\n

3. Akshta Pai et al. Clinical Rationale for a Routine Testing Schedule Using Donor-Derived Cell-Free DNA After Kidney Transplantation . Ann Transplant . 2021;26:e932249.<\/span><\/p>\n<\/section>\n


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