A rapid noninvasive assay for the detection of renal transplant injury.
A rapid noninvasive assay for the detection of renal transplant injury.
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DOI：
10.1097/tp.0b013e318295ee5a
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发表时间：
2013-07-15
期刊：
影响因子：
6.2
通讯作者：
Sarwal MM
中科院分区：
文献类型：
--
作者：
Sigdel TK;Vitalone MJ;Tran TQ;Dai H;Hsieh SC;Salvatierra O;Sarwal MM
血液中供体来源的无细胞 DNA (dd-cfDNA) 的拷贝数与心脏移植中的急性排斥反应 (AR) 相关。我们分析了尿 dd-cfDNA 作为肾移植损伤的替代标志物。对来自男性捐献者的女性受者的 63 份活检匹配的尿液样本（41 份稳定尿样和 22 份同种异体移植损伤样本）进行了 Y 染色体（供体）特异性 dd-cfDNA 分析。所有活检均由一位病理学家进行半定量评分。使用相关性和显着性的标准统计测量。即使在移植物 (STA) 功能稳定时（未检测到 12.26 拷贝），不同患者的尿 dd-cfDNA/μg 尿肌酐也存在基线分散。 AR患者尿dd-cfDNA平均值（20.5±13.9）显着高于STA（2.4±3.3；P<0.0001）或慢性同种异体移植物损伤患者（CAI；2.4±2.4；P=0.001），但与BK病毒肾病（BKVN；20.3±15.7；P=0.98）无差异。在AR和BKVN中，与STA或CAI患者相比，患者内漂移非常显着（AR中为10.3±7.4；BKVN中为12.3±8.4，而STA中为-0.5±3.5；CAI中为2.3±2.6；P<0.05）。尿液 dd-cfDNA 与蛋白质/肌酐比（r=0.48；P<0.014）和计算肾小球滤过率（r=−0.52；P<0.007）相关，但对急性同种异体移植物损伤最敏感（曲线下面积=0.80；P<0.0006；95% 置信区间，0.67-0.93）。肾移植后尿dd-cfDNA具有患者特异性阈值，反映供体器官的凋亡损伤负荷。尿液 dd-cfDNA 的连续监测可以作为供体器官急性损伤的替代敏感生物标志物，但缺乏区分 AR 和 BKVN 损伤的特异性。
The copy number of donor-derived cell-free DNA (dd-cfDNA) in blood correlates with acute rejection (AR) in heart transplantation. We analyzed urinary dd-cfDNA as a surrogate marker of kidney transplant injury. Sixty-three biopsy-matched urine samples (41 stable and 22 allograft injury) were analyzed from female recipients of male donors for chromosome Y (donor)–specific dd-cfDNA. All biopsies were semiquantitatively scored by a single pathologist. Standard statistical measures of correlation and significance were used. There was baseline scatter for urinary dd-cfDNA/µg urine creatinine across different patients, even at the time of stable graft (STA) function (undetected to 12.26 copies). The mean urinary dd-cfDNA in AR (20.5±13.9) was significantly greater compared with STA (2.4±3.3; P<0.0001) or those with chronic allograft injury (CAI; 2.4±2.4; P=0.001) but no different from BK virus nephropathy (BKVN; 20.3±15.7; P=0.98). In AR and BKVN, the intrapatient drift was highly significant versus STA or CAI patients (10.3±7.4 in AR; 12.3±8.4 in BKVN vs. −0.5±3.5 in STA and 2.3±2.6 in CAI; P<0.05). Urinary dd-cfDNA correlated with protein/creatinine ratio (r=0.48; P<0.014) and calculated glomerular filtration rate (r=−0.52; P<0.007) but was most sensitive for acute allograft injury (area under the curve=0.80; P<0.0006; 95% confidence interval, 0.67–0.93). Urinary dd-cfDNA after renal transplantation has patient specific thresholds, reflecting the apoptotic injury load of the donor organ. Serial monitoring of urinary dd-cfDNA can be a surrogate sensitive biomarker of acute injury in the donor organ but lacks the specificity to distinguish between AR and BKVN injury.