Molecular Phenotypes of Acute Kidney Injury in Kidney Transplants
Molecular Phenotypes of Acute Kidney Injury in Kidney Transplants
复制标题
DOI：
10.1681/asn.2011090887
复制
发表时间：
2012-05-01
影响因子：
13.6
通讯作者：
Halloran, Philip F.
中科院分区：
文献类型：
--
作者：
Famulski, Konrad S.;de Freitas, Declan G.;Halloran, Philip F.
由于很少进行活检，因此对阿基肾脏的分子表型知之甚少。然而，所有的肾移植都经历急性损伤，使得早期肾移植成为急性损伤的极好模型，只要没有排斥反应，因为供体肾不应该有CKD，移植后活检相对频繁地发生，并且随访通常是极好的。在这里，我们使用组织病理学和微阵列比较了26例急性损伤移植的适应症活检和11例稳定移植的原始协议活检。急性损伤的肾脏表现出与损伤修复反应相关的394种转录物的表达增加，包括许多上皮样损伤分子组织、重塑分子和炎症分子。许多其他基因也预测了表型，包括急性损伤生物标志物HAVCR 1和IL 18。损伤修复转录本的途径分析揭示了与癌症、发育和细胞运动的相似性。急性损伤肾的损伤修复转录分数与移植肾功能下降、未来肾功能恢复、脑死亡和透析需求相关，但与未来移植肾功能丧失无关。相反，急性肾小管损伤的组织学特征与功能或分子变化无关。因此，与损伤修复相关的转录本表明肾实质对急性损伤的大规模协调反应，提供了用于评估肾活检中损伤严重程度的客观测量和对阿基的许多生物标志物的验证。
Little is known regarding the molecular phenotype of kidneys with AKI because biopsies are performed infrequently. However, all kidney transplants experience acute injury, making early kidney transplants an excellent model of acute injury, provided the absence of rejection, because donor kidneys should not have CKD, post-transplant biopsies occur relatively frequently, and follow-up is excellent typically. Here, we used histopathology and microarrays to compare indication biopsies from 26 transplants with acute injury with 11 pristine protocol biopsies of stable transplants. Kidneys with acute injury showed increased expression of 394 transcripts associated with the repair response to injury, including many epithelium-like injury molecules tissue, remodeling molecules, and inflammation molecules. Many other genes also predicted the phenotype, including the acute injury biomarkers HAVCR1 and IL18. Pathway analysis of the injury-repair transcripts revealed similarities to cancer, development, and cell movement. The injury-repair transcript score in kidneys with acute injury correlated with reduced graft function, future renal recovery, brain death, and need for dialysis, but not with future graft loss. In contrast, histologic features of acute tubular injury did not correlate with function or with the molecular changes. Thus, the transcripts associated with repair of injury suggest a massive coordinated response of the kidney parenchyma to acute injury, providing both an objective measure for assessing the severity of injury in kidney biopsies and validation for many biomarkers of AKI.