The etiology of congenital obstructive uropathy: developmental and genetic perspectives.

Abstract

Congenital obstructive uropathy (COU) encompasses a heterogeneous group of anomalies arising during critical stages of fetal development, which are characterized by functional or structural obstruction of the urinary tract. This obstruction hampers normal urine flow, and the resulting urinary pressure build-up can damage the developing kidneys and bladder. COU pathogenesis is complex and its clinical outcomes are highly variable, ranging from asymptomatic ultrasonographic abnormalities to end-stage kidney disease. This review examines the developmental and genetic mechanisms underlying COU and the associated organ damage, with a focus on intrinsic, isolated forms. Although genetic studies have improved our understanding of the molecular pathways involved in urinary tract maldevelopment, most patients lack a genetic diagnosis. Hence, multiple etiologic factors appear at play, including (epi)genetic and environmental. Closing gaps in our knowledge of kidney and urinary tract development and their interdependency for normal function is essential for developing personalized care to ultimately improve patient outcomes.