Heilman Raymond L, Fleming James N, Park Sook H, Rebello Christabel, Kleiboeker Steve, Holman John, Friedewald John J
Department of Medicine, Mayo Clinic, Phoenix, Arizona.
Medical Affairs, Transplant Genomics, Inc., Framingham, Massachusetts.
Kidney360. 2024 Oct 1;5(10):1534-1542. doi: 10.34067/KID.0000000000000549. Epub 2024 Aug 14.
Peripheral blood biomarkers may have value in monitoring kidney transplant recipients after treatment of acute rejection. The donor-derived cellfree DNA may be more sensitive to identifying antibody-mediated rejection and gene expression profile may be more sensitive to identifying acute cellular rejection.
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 analysis of a multicenter observational study. Patients who had a biopsy-proven acute rejection, 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 patients 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 a sensitivity of 59%, specificity of 76%, positive predictive value (PPV) of 79%, and negative predictive value of 54%. Donor-derived cellfree DNA (dd-cfDNA) demonstrated a sensitivity of 62%, specificity of 86%, PPV of 88%, and negative predictive value 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 T-cell–mediated rejection while dd-cfDNA was more likely to be positive in antibody-mediated rejection.
Both GEP and dd-cfDNA may have utility in identifying clinically stable patients with persistent rejection in need of biopsy; however, they identify different types of rejections.
: NCT01531257.
外周血生物标志物在监测肾移植受者急性排斥反应治疗后可能具有价值。供体来源的游离DNA可能对识别抗体介导的排斥反应更敏感，而基因表达谱可能对识别急性细胞性排斥反应更敏感。
持续性排斥反应是肾移植长期存活日益公认的障碍。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。
这是一项对多中心观察性研究的分析。纳入经活检证实为急性排斥反应、在9个月（270天）内进行了另一次活检且有与活检配对的生物标志物样本的患者。
58例接受重复活检的患者共识别出64次初次排斥反应，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（PPV）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%，PPV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PPV均为100%。GEP在T细胞介导的排斥反应中更可能为阳性，而dd-cfDNA在抗体介导的排斥反应中更可能为阳性。
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中可能都有用；然而，它们识别不同类型的排斥反应。
NCT01531257。
