Manucha Walter
Laboratorio de Fisiología y Fisiopatología Renal, Area de Fisiopatologia, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina.
Biocell. 2007;31(1):1-12.
Congenital obstructive nephropathy is the primary cause of end-stage renal disease in children. Rapid diagnosis and initiation of the treatment are vital to preserve function and/or to slow down renal injury. Obstructive uropathy effects -decline in the plasmatic renal flow and glomerular filtration rate, interstitial infiltrate of leukocytes, significant decrease of the urine concentration, loss of the capacity to concentrate urine as well as fibrosis and apoptosis- are a consequence of a variety of factors that work in complex ways and are still not fully understood. Mediators as angiotensin II, transforming growth factor-beta (TGF-beta) and nitric oxide (NO) have been implicated in congenital obstructive nephropathy. The renin-angiotensin system is regulated in different ways, affecting both renal structure and function, and that it in turn depends upon the duration of the obstruction. On the other hand, the role of nitric oxide in renal injury remains somewhat controversial due to the fact that it can exert opposite effects such as cytoprotective and prooxidant / proapoptotic efects as well as proinflammatory and anti-inflammatory effects. In addition, reactive oxidative species (ROS) might contribute to the progression of renal disease. During unilateral ureteral obstruction induced uncoordinated and aberrant growth may lead to the loss of cellular phenotype and apoptosis. Promoting inflammatory responses, the oxidizers can regulate the adherence of certain molecules and proinflammatory mediators, transcription factors and fibrogenic cytokines, that are clearly involved in the progression of renal disease. The congenital obstructive nephropathy is characterized by tubular atrophy, cellular proliferation, apoptosis and fibrosis; immature kidney is more susceptible than adult kidney to showing the above mentioned alterations. Apoptosis seems to be the principal mechanism that leads to tubular atrophy during the neonatal unilateral ureteral obstruction (UUO). Considering the significant role of the apoptosis in UUO, we believe of big interest the study of the regulatory factors of apoptosis in the renal obstruction neonatal. The complex biochemical and molecular events during the development, maintenance and progression of the renal injury in unilateral ureteral obstruction require further major studies to better understand the alterations mentioned above.
先天性梗阻性肾病是儿童终末期肾病的主要病因。快速诊断并开始治疗对于保留肾功能和/或减缓肾损伤至关重要。梗阻性尿路病的影响——肾血浆流量和肾小球滤过率下降、白细胞间质浸润、尿浓缩显著降低、尿浓缩能力丧失以及纤维化和细胞凋亡——是多种因素以复杂方式起作用的结果,目前仍未完全了解。血管紧张素II、转化生长因子-β(TGF-β)和一氧化氮(NO)等介质与先天性梗阻性肾病有关。肾素-血管紧张素系统以不同方式受到调节,影响肾脏结构和功能,而这又反过来取决于梗阻的持续时间。另一方面,一氧化氮在肾损伤中的作用仍存在一定争议,因为它可产生相反的作用,如细胞保护和促氧化/促凋亡作用以及促炎和抗炎作用。此外,活性氧(ROS)可能促进肾病进展。在单侧输尿管梗阻期间,不协调和异常的生长可能导致细胞表型丧失和细胞凋亡。氧化剂通过促进炎症反应,可调节某些分子、促炎介质、转录因子和促纤维化细胞因子的黏附,这些显然都参与了肾病的进展。先天性梗阻性肾病的特征是肾小管萎缩、细胞增殖、细胞凋亡和纤维化;未成熟肾脏比成年肾脏更容易出现上述改变。细胞凋亡似乎是新生儿单侧输尿管梗阻(UUO)期间导致肾小管萎缩的主要机制。考虑到细胞凋亡在UUO中的重要作用,我们认为研究新生儿肾梗阻中细胞凋亡的调节因子具有重大意义。单侧输尿管梗阻时肾损伤发生、发展和进展过程中复杂的生化和分子事件需要进一步深入研究,以更好地理解上述改变。