Gomez-Alamillo C, Ramos-Barron M A, Benito-Hernandez A, Rodrigo E, Ruiz J C, Agüeros C, Sanchez M, Arias M
Nephrology Department, Marques de Valdecilla Hospital, University of Cantabria, Institute for Investigation "Marques de Valdecilla" (IFIMAV), Santander, Cantabria, Spain.
Transplant Proc. 2012 Nov;44(9):2573-6. doi: 10.1016/j.transproceed.2012.09.100.
Renal dysfunction due to acute rejection (AR), acute tubular necrosis, or calcineurin inhibitors toxicity is related to development of interstitial fibrosis/tubular atrophy (IF/TA) and graft survival. Determination of serum creatinine (sCr) displays poor sensitivity as a marker for early detection of graft dysfunction. Kidney biopsy is an accurate but invasive procedure for the diagnosis. The levels of urinary mRNA of genes that regulate epithelial-mesenchymal transition (EMT) can reflect early damage and detect the development of IF/TA. Repeated studies of these genes can provide noninvasive information about the evolution of the graft, facilitating early diagnosis and treatment.
To analyze the relationships between early and 1-year graft evolution in relation to gene expression of EMT biomarkers.
Seventy-one kidney transplant recipients were monitored during 1 year recording analytical, clinical, and histological (if available) data. We determined RNA gene expression of EMT, angiotensinogen, E-cadherin, N-cadherin, transforming growth factor (TGF) beta and bone morphogenetic patients 7 (BMP7).
At 3 months, angiotensinogen (mean [standard deviation]), (2.42 [.66] versus 8.58 [3.24]; P = .017) and N-cadherin (0.59 [0.26] versus 3.15 [1.35]; P = .016) discriminate a good evolution from AR episodes BMP-7 discriminated a good evolution versus AR (0.72 [0.29] versus 4.53 [2.23]; P = .006) and delayed graft function versus AR (1.14 [0.79] versus 4.53 [2.23]; P = .049). After 1 year, the ratio TGF-beta/BMP7 discriminated patients with an sCr > 1.5 mg/dL (6614.6 [1063.6] versus 3378.7 [1019]; P = .034). There was a positive correlation between urinary and tissue TGF-beta [r = 59; P = .003].
The expression of studied genes reverting EMT at 3 months postransplantation showed differences in initial graft evolution. At 1 year, the TGF-beta/BMP7 ratio suggested activation of EMT, possible early marker of renal dysfunction.
急性排斥反应（AR）、急性肾小管坏死或钙调神经磷酸酶抑制剂毒性所致的肾功能障碍与间质纤维化/肾小管萎缩（IF/TA）的发生及移植物存活相关。血清肌酐（sCr）测定作为移植物功能障碍早期检测的标志物，敏感性较差。肾活检是诊断的准确方法，但具有侵入性。调节上皮-间质转化（EMT）的基因的尿mRNA水平可反映早期损伤并检测IF/TA的发展。对这些基因的重复研究可为移植物的演变提供非侵入性信息，有助于早期诊断和治疗。
分析EMT生物标志物基因表达与移植物早期及1年演变之间的关系。
对71例肾移植受者进行为期1年的监测，记录分析、临床和组织学（如可用）数据。我们测定了EMT、血管紧张素原、E-钙黏蛋白、N-钙黏蛋白、转化生长因子（TGF）β和骨形态发生蛋白7（BMP7）的RNA基因表达。
在3个月时，血管紧张素原（均值[标准差]），（2.42[.66]对8.58[3.24]；P =.017）和N-钙黏蛋白（0.59[0.26]对3.15[1.35]；P =.016）可区分AR发作后的良好演变。BMP-7可区分与AR相比的良好演变（0.72[0.29]对4.53[2.23]；P =.006）以及与AR相比的移植肾功能延迟（1.14[0.79]对4.53[2.23]；P =.049）。1年后，TGF-β/BMP7比值可区分sCr>1.5mg/dL的患者（6614.6[1063.6]对3378.7[1019]；P =.034）。尿TGF-β与组织TGF-β之间存在正相关[r = 59；P =.003]。
移植后3个月时逆转EMT的研究基因的表达在移植物的初始演变中显示出差异。在1年时，TGF-β/BMP7比值提示EMT激活，可能是肾功能障碍的早期标志物。
