Yosypiv Ihor V
Section of Pediatric Nephrology, Department of Pediatrics, Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Int J Nephrol. 2012;2012:909083. doi: 10.1155/2012/909083. Epub 2012 May 20.
Congenital anomalies of the kidney and urinary tract (CAKUTs) occur in 3-6 per 1000 live births, account for the most cases of pediatric end-stage kidney disease (ESKD), and predispose an individual to hypertension and cardiovascular disease throughout life. Although CAKUTs are a part of many known syndromes, only few single-candidate causative genes have been implicated so far in nonsyndromic cases of human CAKUT. Evidence from mouse models supports the hypothesis that non-syndromic human CAKUT may be caused by single-gene defects. Because increasing numbers of children with CAKUT are surviving to adulthood, better understanding of the molecular pathogenesis of CAKUT, development of new strategies aiming at prevention of CAKUT, preservation of renal function, and avoidance of associated cardiovascular morbidity are needed. In this paper, we will focus on the knowledge derived from the study of syndromic and non-syndromic forms of CAKUT in humans and mouse mutants to discuss the role of genetic, epigenetic, and in utero environmental factors in the pathogenesis of non-syndromic forms of CAKUT in children with particular emphasis on the genetic contributions to CAKUT.
先天性肾脏和尿路畸形（CAKUT）在每1000例活产中出现3至6例，是儿童终末期肾病（ESKD）的主要病因，并且会使人一生中易患高血压和心血管疾病。尽管CAKUT是许多已知综合征的一部分，但迄今为止，在人类非综合征性CAKUT病例中，只有少数单候选致病基因被牵连。来自小鼠模型的证据支持这样的假说，即非综合征性人类CAKUT可能由单基因缺陷引起。由于越来越多患有CAKUT的儿童存活至成年，因此需要更好地了解CAKUT的分子发病机制，制定旨在预防CAKUT、保护肾功能以及避免相关心血管疾病的新策略。在本文中，我们将重点关注从人类和小鼠突变体的综合征性和非综合征性CAKUT研究中获得的知识，以讨论遗传、表观遗传和子宫内环境因素在儿童非综合征性CAKUT发病机制中的作用，特别强调基因对CAKUT的影响。
