Heilman Raymond L, Fleming James N, Park Sook H, Rebello Christabel, Kleiboeker Steve, Holman John, Friedewald John J
Department of Medicine, Mayo Clinic, Phoenix, AZ.
Medical Affairs, Transplant Genomics, Inc, Framingham, MA.
Kidney360. 2024 Aug 14. doi: 10.34067/KID.0000000000000549.
Persistent rejection is an increasingly recognized barrier to long-term kidney allograft survival. A noninvasive method to help identify patients with persistent rejection in need of biopsy would be valuable.
This was a post-hoc analysis of a multicenter observational study. Subjects that had a biopsy-proven acute rejection and had another biopsy within 9 months (270 days) and had a biopsy-paired biomarker sample were included.
A total of 64 "index" rejections in 58 subjects with repeat biopsies were identified with a median time to repeat biopsy of 100 days. Persistent rejection was present in 61%; 69% of follow-up biopsies were performed in clinically stable patients. Peripheral blood gene expression profile (GEP) demonstrated 59% sensitivity, 76% specificity, PPV of 79%, and NPV of 54%. Donor-derived cell-free DNA (dd-cfDNA) demonstrated sensitivity of 62%, specificity of 86%, PPV of 88%, and NPV of 56%. For repeat biopsies within 90 days of rejection in clinically stable patients (63% of repeat biopsies), both GEP and dd-cfDNA had specificities and PPVs of 100%. GEP was more likely to be positive in TCMR, while dd-cfDNA was more likely to be positive in AMR.
Both GEP and dd-cfDNA may have utility at identifying clinically stable patients with persistent rejection in need of biopsy, however they identify different types of rejection.
持续性排斥反应是长期肾移植存活中日益被认识到的障碍。一种有助于识别需要活检的持续性排斥反应患者的非侵入性方法将很有价值。
这是一项多中心观察性研究的事后分析。纳入经活检证实有急性排斥反应且在9个月（270天）内进行了另一次活检并有活检配对生物标志物样本的受试者。
在58例接受重复活检的受试者中，共识别出64次“指数”排斥反应，重复活检的中位时间为100天。61%存在持续性排斥反应；69%的随访活检是在临床稳定的患者中进行的。外周血基因表达谱（GEP）显示敏感性为59%，特异性为76%，阳性预测值为79%，阴性预测值为54%。供体来源的游离DNA（dd-cfDNA）显示敏感性为62%，特异性为86%，阳性预测值为88%，阴性预测值为56%。对于临床稳定患者在排斥反应90天内进行的重复活检（占重复活检的63%），GEP和dd-cfDNA的特异性和阳性预测值均为100%。GEP在TCMR中更可能为阳性，而dd-cfDNA在AMR中更可能为阳性。
GEP和dd-cfDNA在识别需要活检的持续性排斥反应的临床稳定患者方面可能都有用，但它们识别不同类型的排斥反应。
