Mechanisms of renal injury and progression of renal disease in congenital obstructive nephropathy
Mechanisms of renal injury and progression of renal disease in congenital obstructive nephropathy
复制标题
DOI：
10.1007/s00467-009-1316-5
复制
发表时间：
2010-04-01
影响因子：
3
通讯作者：
Kiley, Susan C.
中科院分区：
文献类型：
--
作者：
Chevalier, Robert L.;Thornhill, Barbara A.;Kiley, Susan C.
先天性阻塞性肾病占儿童慢性肾病的最大比例。导致病变的遗传和非遗传因素在很大程度上是未知的，人们的注意力集中在最小化阻塞性肾损伤和优化长期预后上。动物模型已经阐明了导致发育中的肾脏梗阻性损伤的细胞和分子事件。这些研究揭示了通过细胞表型转变和细胞死亡导致肾单位损失，导致非小管肾小球的形成和小管萎缩。生长因子和细胞因子的表达改变，包括血管紧张素、转化生长因子- β和粘附分子，通过肾小球、小管和血管细胞的凋亡或表型转变调节细胞死亡。细胞损伤的介质包括缺氧、缺血和活性氧，而成纤维细胞则随着细胞外基质沉积的增加而发生肌成纤维细胞转化。病变的进展包括间质性炎症和间质性纤维化，两者都损害梗阻肾脏的生长并导致对侧肾脏的代偿性生长。长期结果取决于梗阻的时间和严重程度及其缓解，减少持续损伤和增强重塑。进展将取决于新的生物标志物来评估梗阻的严重程度，确定治疗方法，并跟踪病变的演变。
Congenital obstructive nephropathy accounts for the greatest fraction of chronic kidney disease in children. Genetic and nongenetic factors responsible for the lesions are largely unidentified, and attention has been focused on minimizing obstructive renal injury and optimizing long-term outcomes. The cellular and molecular events responsible for obstructive injury to the developing kidney have been elucidated from animal models. These have revealed nephron loss through cellular phenotypic transition and cell death, leading to the formation of atubular glomeruli and tubular atrophy. Altered renal expression of growth factors and cytokines, including angiotensin, transforming growth factor-beta, and adhesion molecules, modulate cell death by apoptosis or phenotypic transition of glomerular, tubular, and vascular cells. Mediators of cellular injury include hypoxia, ischemia, and reactive oxygen species, while fibroblasts undergo myofibroblast transformation with increased deposition of extracellular matrix. Progression of the lesions involves interstitial inflammation and interstitial fibrosis, both of which impair growth of the obstructed kidney and result in compensatory growth of the contralateral kidney. The long-term outcome depends on timing and severity of the obstruction and its relief, minimizing ongoing injury, and enhancing remodeling. Advances will depend on new biomarkers to evaluate the severity of obstruction, to determine therapy, and to follow the evolution of lesions.