Oellerich Michael, Budde Klemens, Osmanodja Bilgin, Bornemann-Kolatzki Kirsten, Beck Julia, Schütz Ekkehard, Walson Philip D
Department of Clinical Pharmacology, University Medical Center Göttingen, Göttingen, Germany.
Department of Nephrology and Intensive Care, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Front Genet. 2022 Oct 21;13:1031894. doi: 10.3389/fgene.2022.1031894. eCollection 2022.
There is a need to improve personalized immunosuppression in organ transplantation to reduce premature graft loss. Biomarkers are needed to better detect rejection, asymptomatic graft injury, and under-immunosuppression. Assessment of minimal necessary exposure to guide tapering and prevent immune activation is also important. There is robust clinical evidence from a large number of published studies supporting the role of dd-cfDNA for monitoring graft integrity and detection or exclusion of rejection. Dd-cfDNA indicates graft cell death without being rejection specific. It can be determined in plasma through droplet digital PCR using preselected SNPs or next generation sequencing. Changes in recipient cfDNA (e.g., by infection) can affect the results of dd-cfDNA fractional determination. This limitation can be overcome using absolute dd-cfDNA quantification. The combination of fractional and absolute determination including total cfDNA is recommended for meaningful interpretation of the results. The value proposition for the patient includes earlier transplant injury detection and intervention, less full blown rejection risk, an alternative to invasive biopsies, and personalized immunosuppression with potential for improved long-term outcome. Transplant physicians benefit from better immunosuppressive guidance and having an alternative when biopsies are refused or contraindicated. Further advantages are improved biopsy interpretation, less trial and error changes in immunosuppression, and less time dealing with complications. The laboratory medicine specialist can provide more effective services. Hospital management and insurance companies could benefit from more cost-effective surveillance of transplant recipients. Potential cost savings would result from fewer biopsies as a result of the tests' high negative predictive value, fewer re-transplantations, and less organ failure with return to dialysis. A pathway to implementation and metrics is suggested to measure the effectiveness of dd-cfDNA testing.
有必要改进器官移植中的个性化免疫抑制，以减少移植物过早丢失。需要生物标志物来更好地检测排斥反应、无症状移植物损伤和免疫抑制不足。评估最小必要暴露以指导减药并防止免疫激活也很重要。大量已发表研究的有力临床证据支持dd-cfDNA在监测移植物完整性以及检测或排除排斥反应中的作用。Dd-cfDNA指示移植物细胞死亡，但并非特异性针对排斥反应。它可以通过使用预选单核苷酸多态性的数字液滴PCR或下一代测序在血浆中测定。受者cfDNA的变化（例如由于感染）会影响dd-cfDNA分数测定的结果。使用绝对dd-cfDNA定量可以克服这一局限性。为了对结果进行有意义的解释，建议将分数测定和绝对测定（包括总cfDNA）相结合。对患者的价值主张包括更早检测和干预移植损伤、降低完全性排斥反应风险、替代侵入性活检以及个性化免疫抑制，有可能改善长期预后。移植医生受益于更好的免疫抑制指导，并且在活检被拒绝或有禁忌时拥有替代方法。进一步的优势包括改善活检解释、减少免疫抑制的反复试验性调整以及减少处理并发症的时间。检验医学专家可以提供更有效的服务。医院管理层和保险公司可以从对移植受者更具成本效益的监测中受益。由于该检测具有较高的阴性预测价值，减少了活检次数、再次移植次数以及器官衰竭并恢复透析的情况，可能会节省成本。建议采用一条实施途径和指标来衡量dd-cfDNA检测的有效性。
