Section of Pediatric Nephrology, Department of Pediatrics, Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Pediatr Nephrol. 2011 Mar;26(3):353-64. doi: 10.1007/s00467-010-1629-4. Epub 2010 Aug 27.
Congenital anomalies of the kidney and urinary tract (CAKUT) occur in 1 in 500 births and are a major cause of morbidity in children. Notably, CAKUT account for the most cases of pediatric end-stage renal disease and predispose the individual to hypertension and cardiovascular disease throughout life. Although some forms of CAKUT are a part of a syndrome or are associated with a positive family history, most cases of renal system anomalies are sporadic and isolated to the urinary tract. Broad phenotypic spectrum of CAKUT and variability in genotype-phenotype correlation indicate that pathogenesis of CAKUT is a complex process that depends on interplay of many factors. This review focuses on the genetic mechanisms (single-gene mutations, modifier genes) leading to renal system anomalies in humans and discusses emerging insights into the role of epigenetics, in utero environmental factors, and micro-RNAs (miRNAs) in the pathogenesis of CAKUT. Common gene networks that function in defined temporospatial fashion to orchestrate renal system morphogenesis are highlighted. Derangements in cellular, molecular, and morphogenetic mechanisms that direct normal renal system development are emphasized as a major cause of CAKUT. Integrated understanding of how morphogenetic process disruptions are linked to CAKUT will enable improved diagnosis, treatment, and prevention of congenital renal system anomalies and their consequences.
先天性肾和尿路畸形（CAKUT）在每 500 例出生中就有 1 例发生，是儿童发病的主要原因。值得注意的是，CAKUT 占儿童终末期肾病的大多数病例，并使个体终生易患高血压和心血管疾病。尽管某些形式的 CAKUT 是综合征的一部分或与阳性家族史相关，但大多数泌尿系统畸形病例都是散发性和孤立性的。CAKUT 的广泛表型谱和基因型-表型相关性的可变性表明，CAKUT 的发病机制是一个复杂的过程，取决于许多因素的相互作用。本综述重点介绍导致人类肾脏系统异常的遗传机制（单基因突变、修饰基因），并讨论了表观遗传学、子宫内环境因素和 microRNAs（miRNAs）在 CAKUT 发病机制中的作用的新见解。突出强调了在特定时空方式下发挥作用以协调肾脏系统形态发生的常见基因网络。强调了指导正常肾脏系统发育的细胞、分子和形态发生机制的紊乱是 CAKUT 的主要原因。综合了解形态发生过程的中断如何与 CAKUT 相关联将能够改善先天性肾脏系统异常及其后果的诊断、治疗和预防。
