Urinary and plasma donor-derived cell-free DNA for noninvasive monitoring of BK polyomavirus-associated nephropathy in kidney transplant recipients: a prospective cohort study.
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引用次数: 0
Abstract
Background: BK polyomavirus-associated nephropathy (BKPyVAN) is a major cause of allograft injury and dysfunction in kidney transplant recipients. Current monitoring tools, including viremia and biopsy, have limitations in sensitivity, invasiveness, and timing.
Objective: To evaluate donor-derived cell-free DNA (dd-cfDNA) in urine and plasma as a dynamic, noninvasive biomarker for monitoring treatment response and predicting rejection risk in patients with biopsy-proven BKPyVAN.
Methods: In this prospective cohort study, 25 kidney transplant recipients with biopsy-proved BKPyVAN were enrolled and stratified into two cohorts: conventional immunosuppression reduction (CISR, n = 20) and early immunosuppression reduction (EISR, n = 5). A total of 224 urine and plasma samples were collected before biopsy and at 1, 2, 3, and 6 months post-biopsy. dd-cfDNA levels were quantified and correlated with histological features and clinical outcomes.
Results: Urinary dd-cfDNA levels significantly declined in the CISR cohort by month 2 (p < 0.01), preceding changes in creatinine and BKPyV reads. In the EISR cohort, urinary dd-cfDNA levels remained stable, suggesting early therapeutic response. Plasma dd-cfDNA effectively identified acute rejection, with elevations in two CISR patients. Histologic injury patterns, including edema and cast formation, correlated with urinary dd-cfDNA concentrations (r = 0.44-0.51, p < 0.05).
Conclusion: Combined urinary and plasma dd-cfDNA measurements are promising for noninvasive, dynamic surveillance of BKPyVAN and rejection risk in kidney transplant recipients. Larger, multicenter studies are warranted to define clinical thresholds and standardize integration into immunosuppression management.
背景：BK多瘤病毒相关性肾病（BKPyVAN）是肾移植受者同种异体移植损伤和功能障碍的主要原因。目前的监测工具，包括病毒血症和活检，在敏感性、侵入性和时间上都有局限性。目的：评估尿液和血浆供体来源的无细胞DNA （dd-cfDNA）作为一种动态、无创的生物标志物，用于监测活检证实的BKPyVAN患者的治疗反应和预测排斥风险。方法：在这项前瞻性队列研究中，入选了25例活检证实的BKPyVAN肾移植受者，并将其分为两组：常规免疫抑制减少组（CISR, n = 20）和早期免疫抑制减少组（EISR, n = 5）。在活检前和活检后1、2、3和6个月共收集尿液和血浆样本224份。定量dd-cfDNA水平，并与组织学特征和临床结果相关。结果：在CISR队列中，尿液dd-cfDNA水平在第2个月显著下降（p r = 0.44-0.51）。结论：联合尿液和血浆dd-cfDNA检测有望无创、动态监测肾移植受者的BKPyVAN和排斥风险。更大的、多中心的研究是必要的，以确定临床阈值，并标准化整合到免疫抑制管理中。
期刊介绍：
Renal Failure primarily concentrates on acute renal injury and its consequence, but also addresses advances in the fields of chronic renal failure, hypertension, and renal transplantation. Bringing together both clinical and experimental aspects of renal failure, this publication presents timely, practical information on pathology and pathophysiology of acute renal failure; nephrotoxicity of drugs and other substances; prevention, treatment, and therapy of renal failure; renal failure in association with transplantation, hypertension, and diabetes mellitus.
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