Transcriptional Profiles in Urine During Acute Rejection, Bacteriuria, CMV Infection and Stable Graft Function After Renal Transplantation
Transcriptional Profiles in Urine During Acute Rejection, Bacteriuria, CMV Infection and Stable Graft Function After Renal Transplantation
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DOI：
10.1111/j.1365-3083.2009.02226.x
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发表时间：
2009-04-01
影响因子：
3.7
通讯作者：
Carstens, J.
中科院分区：
文献类型：
--
作者：
Ozbay, A.;Torring, C.;Carstens, J.
急性排斥反应仍然是移植肾功能不全的重要原因，准确的诊断是成功治疗移植受者的关键。尿液中的分子标记物可作为急性排斥反应的诊断工具，但关于这些生物标记物的独特性仍存在争议。我们检测了24例急性排斥反应、12例菌尿、11例巨细胞病毒（CMV）感染和17例移植肾功能稳定的对照组肾移植受者尿标本中穿孔素（PRF）、颗粒酶B（GZMB）和颗粒溶素（GNLY）的mRNA，并将其标准化为亲环素B。使用实时聚合酶链反应测定进行测量。mRNA水平与对照组相比，急性排斥反应受者中所有三种标志物的平均值[95% CI]显著更高：PRF（0.23 [0.12-0.42] vs 0.04 [0.02-0.07] P < 0.001），GZMB（0.14 [0.09-0.23] vs 0.05 [0.03-0.08] P = 0.003），GNLY（0.24 [0.14-0.41] vs 0.06 [0.03-0.11] P = 0.001）。急性排斥反应时GZMB和GNLY水平显著高于菌尿（P = 0.011和P = 0.005），急性排斥反应时PRF水平显著高于CMV感染（P = 0.015）。在菌尿和CMV感染期间与对照组比较标记物水平时，未发现显著差异。与移植物功能稳定的受者相比，在急性排斥反应期间，尿PRF、GZMB和GNLY的mRNA水平显著升高，但在菌尿或CMV感染期间不显著升高。只有某些标记物具有区分急性排斥反应与菌尿和CMV感染的能力，这就是为什么在将该技术应用于临床实践之前应仔细考虑的原因。
Acute rejection remains an important cause of renal allograft dysfunction and the need for accurate diagnosis is essential to treat transplant recipients successfully. Molecular markers in urine may serve as a diagnostic tool in acute rejection, but controversy still exists regarding the uniqueness of these biomarkers. We measured mRNA of perforin (PRF), granzyme B (GZMB) and granulysin (GNLY) normalized to cyclophilin B in urine specimens from 24 renal allograft recipients with acute rejection, 12 with bacteriuria, 11 with cytomegalovirus (CMV) infections and 17 controls with stable graft function. Measurements were performed using a real-time polymerase chain reaction assay. mRNA levels (means [95% CI]) for all three markers were significantly higher in recipients with acute rejection compared with controls: PRF (0.23 [0.12-0.42] versus 0.04 [0.02-0.07] P < 0.001), GZMB (0.14 [0.09-0.23] versus 0.05 [0.03-0.08] P = 0.003), GNLY (0.24 [0.14-0.41] versus 0.06 [0.03-0.11] P = 0.001). GZMB and GNLY levels during acute rejection were significantly higher when compared with bacteriuria (P = 0.011 and P = 0.005 respectively), and PRF level during acute rejection was significantly elevated compared with CMV infection (P = 0.015). No significant difference was found when comparing marker levels during bacteriuria and CMV infection to controls. Urinary mRNA levels of PRF, GZMB and GNLY are significantly elevated during acute rejection but not during bacteriuria or CMV infections when compared with recipients with stable graft function. The ability to differentiate acute rejection from bacteriuria and CMV infections was only present for some of the markers, that is why careful consideration should be given before applying this technique to clinical practice.