Chapter 19 - Vesicoureteral Obstruction and Vesicoureteral Reflux: Different Congenital Defects With a Common Cause

Abstract

Removal of toxic substances from the blood depends on patent connections among the kidneys, ureters, and bladder that are established when the ureter moves from the original insertion site in the nephric duct to the bladder trigone, the final insertion site. A number of studies provide new insights into the normal process of ureter maturation that, when abnormal, results in vesicoureteral obstruction, vesicoureteral reflux, and hydronephrosis, pathologies that affect 1–2% of the human population and are a major cause of renal disease in children. According to the Ureteric Bud Theory of Mackie and Stephens, proper positioning of the distal ureter depends on differentiation of the common nephric duct, the caudal-most nephric duct segment, into the trigone, a muscular structure at the bladder neck that marks the junction between the ureteral and sex duct insertion sites. The availability of mouse models has enabled us to reexamine this hypothesis in the context of normal and abnormal development. We find that nephric duct insertion, an event that occurs before ureteric bud formation, is critical for proper positioning of the distal ureter in the bladder. Our studies indicate that, unlike what has been thought, the common nephric duct does not differentiate into the bladder trigone but instead undergoes a continuous process of apoptosis as it is adsorbed into the urogenital sinus. These cellular rearrangements bring the distal ureter close to the urogenital sinus, separate the ureter from the common nephric duct, and promote insertion of the distal ureter into the urogenital sinus. Once inserted, growth of the urogenital sinus, in particular the bladder neck, moves the distal ureter farther from the nephric duct. Failure at any of these steps can result in ectopically positioned distal ureters, leading to vesicoureteral reflux or obstruction, depending on the final position of the ureter orifice relative to the trigone.