Pre-natal Development of the Kidneys and Urinary Tract

Abstract

The mammalian kidney and lower urinary tract maintains and regulates water balance, acid-base homeostasis, electrolyte equilibrium, and waste excretion. The performance of these activities depends on the development of specific cell types in a precise temporal and spatial pattern. Defects in the process can lead to insufficient numbers of nephrons and/or dysfunctional ureters and/or bladders that fail to propel urine forward leading to secondary renal defects. Over the past several decades, considerable advances have been made in understanding the molecular basis for this developmental program. Defects in this program result in congenital anomalies of the kidney and urinary tract (CAKUT), which are leading causes of chronic kidney disease and renal failure in children. These developmental disorders range from renal malformations, such as renal aplasia (absence of the kidney), dysplasia (failure of normal renal differentiation), and hypoplasia (smaller kidneys), to urinary tract abnormalities such as hydronephrosis, vesicoureteral reflux, and duplicated collecting systems. Moreover, many of the molecules identified in animal models as critical for renal development have been validated as important in human CAKUT. This chapter describes renal embryology and molecular control of kidney and urinary tract development, as a means to understand the developmental origins of human CAKUT.