Rizvi Asim, Faiz Sara, Thakkar Parin H, Hussain Syed, Gamilla-Crudo Ann N, Kueht Michael, Mujtaba Muhammad A
Department of Nephrology, Hypertension and Transplant Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
J Pers Med. 2023 Jul 29;13(8):1205. doi: 10.3390/jpm13081205.
Donor-derived cell-free DNA (dd-cfDNA) may safely assess kidney allograft rejection. Molecular Microscope (MMDx) gene expression may offer increased precision to histology. This single-center retrospective study monitored kidney transplant recipients for rejection at specified time intervals by utilizing creatinine (SCr), proteinuria, donor-specific antibodies (DSAs), and dd-cfDNA. A clinically indicated biopsy sample was sent for histopathology and MMDx. Patients were categorized into rejection (Rej) and non-rejection (NRej) groups, and further grouped according to antibody-mediated rejection (ABMR) subtypes. Rej and NRej groups included 52 and 37 biopsies, respectively. Median follow-up duration was 506 days. DSAs were positive in 53% and 22% of patients in both groups, respectively ( = 0.01). Among these groups, pre- and post-intervention median SCr, proteinuria, and dd-cfDNA at 1 month, 2 months, and at the last follow-up revealed significant difference for dd-cfDNA (all = 0.01), however, no difference was found for SCr and proteinuria ( > 0.05). The AUC was 0.80 (95% CI: 0.69-0.91), with an optimal dd-cfDNA criterion of 2.2%. Compared to histology, MMDx was more likely to diagnose ABMR (79% vs. 100%) with either C4d positivity or negativity and/or DSA positivity or negativity. Hence, a pre- and post-intervention allograft monitoring protocol in combination with dd-cfDNA, MMDx, and histology has aided in early diagnosis and timely individualized intervention.
供体来源的游离DNA（dd-cfDNA）可安全地评估肾移植排斥反应。分子显微镜（MMDx）基因表达可能会提高组织学诊断的准确性。这项单中心回顾性研究通过检测血清肌酐（SCr）、蛋白尿、供体特异性抗体（DSA）和dd-cfDNA，在特定时间间隔对肾移植受者进行排斥反应监测。将临床指示的活检样本送去进行组织病理学检查和MMDx检测。患者被分为排斥反应（Rej）组和非排斥反应（NRej）组，并根据抗体介导的排斥反应（ABMR）亚型进一步分组。Rej组和NRej组分别有52例和37例活检病例。中位随访时间为506天。两组中DSA阳性的患者分别占53%和22%（P = 0.01）。在这些组中，干预前后1个月、2个月及最后一次随访时的中位SCr、蛋白尿和dd-cfDNA显示，dd-cfDNA有显著差异（均P = 0.01），然而，SCr和蛋白尿无差异（P>0.05）。曲线下面积（AUC）为0.80（95%可信区间：0.69 - 0.91），最佳dd-cfDNA标准为2.2%。与组织学相比，无论C4d阳性或阴性和/或DSA阳性或阴性，MMDx更有可能诊断ABMR（79%对100%）。因此，结合dd-cfDNA、MMDx和组织学的移植前后监测方案有助于早期诊断和及时的个体化干预。
