Geniturinario

Pediatr Nephrol (2009) 24:1621–1632 DOI 10.1007/s00467-008-1072-y

REVIEW

Genetic and developmental basis for urinary tract obstruction
Feng Chen

Received: 23 October 2008 / Revised: 15 November 2008 / Accepted: 18 November 2008 / Published online: 16 December 2008 # IPNA 2008

Abstract Urinary tract obstruction results in obstructive nephropathy and uropathy. It is the most frequentcause of renal failure in infants and children. In the past two decades studies of transgenic models and humans have greatly enhanced our understanding of the genetic factors and developmental processes important in urinary tract obstruction. The emerging picture is that development of the urinary tract requires precise integration of a variety of progenitor cell populations of different embryonicorigins. Such integration is controlled by an intricate signaling network that undergoes dynamic changes as the embryo develops. Most congenital forms of urinary tract obstruction result from the disruption of diverse factors and genetic pathways involved in these processes, especially in the morphogenesis of the urinary conduit or the functional aspects of the pyeloureteral peristaltic machinery.Keywords Urinary tract obstruction . Genetic mutation . Development . Obstructive nephropathy . Obstructive uropathy

also used to describe the failure of urine transport from the kidney to the ureter in the absence of physical blockage. In this review, we use the word “obstruction” to describe both physical obstruction of the urinary tract and functional obstruction [4, 5]. There have beenmany comprehensive reviews on the pathological outcomes and treatment options for obstructive nephropathy and uropathy [2, 6–10]. This review focuses on the recent advances in the understanding of the genetic and developmental causes of UTO, especially the congenital and hereditary forms.

Diverse causes of urinary tract obstruction UTO is categorized by its location and/or cause [11] (Fig. 1).Obstruction at the junction between the ureter and the renal pelvis is called ureteropelvic junction (UPJ) obstruction, presenting as hydronephrosis without obvious dilatation of the ureter. Urine blockage at the ureterovesical junction (UVJ) and the backflow of urine from the bladder to the ureter are described as UVJ obstruction and vesicoureteral reflux (VUR), respectively. Although VUR can occuralong with other urinary tract anomalies, including anatomical obstruction of the urinary tract, VUR does not necessarily lead to upper urinary tract damage by itself. Interruption of urine flow from the bladder to the outside environment through the urethra is called bladder outlet obstruction. The presence of posterior urethral valves is the most common type of bladder outlet obstruction inboys. Although not all of the terms described above directly describe the cause of the problem, the location of the urine flow interruption is taken into consideration in determining etiology. Obstruction can be caused by factors both within and outside the urinary system. Within the urinary system, developmental anomalies can result in anatomical blockage

Introduction Urinary tract obstruction(UTO) can lead to hydroureter, hydronephrosis, and even renal failure [1–3]. It is a condition that concerns both nephrologists and urologists. In a strict sense, UTO describes the presence of a physical blockage to urine flow. However, the word “obstruction” is
F. Chen (*) Renal Division, Department of Internal Medicine, Department of Cell Biology and Physiology, Washington University School ofMedicine, Campus Box 8126, St. Louis, MO 63110, USA e-mail: fchen@DOM.wustl.edu

1622 Fig. 1 Causative factors of UTO. UPJ, UVJ, and bladder outlet obstructions are in italics as these terms describe the location but not the causes of the obstruction

Pediatr Nephrol (2009) 24:1621–1632

Tubular dysfunction (leading to calculus formation)

Pacemaker dysfunction

UPJ obstruction

Smooth...