Kidney embryology is the study of how the kidneys form and develop before birth. Kidneys are paired organs responsible for filtering blood, removing waste products, and maintaining the body’s fluid and electrolyte balance. Understanding this intricate developmental process helps explain how these organs function and how various health conditions, including congenital kidney anomalies, can arise when development goes awry.
Initial Stages of Kidney Development
Early in human embryonic development, the kidneys appear in a sequence of three transient structures: the pronephros, mesonephros, and metanephros. These structures derive from the intermediate mesoderm. The pronephros is the first and most immature form, appearing around day 22 of gestation in the cervical region of the embryo. It consists of tubules called nephrotomes that connect to a pronephric duct, but this structure is considered non-functional in humans and largely degenerates by week 4 or 5.
As the pronephros regresses, the mesonephros develops caudally in the thoracolumbar region, starting around the end of the fourth week. The pronephric duct extends to become the mesonephric duct, also known as the Wolffian duct, which induces the formation of mesonephric tubules in the adjacent intermediate mesoderm. These mesonephric tubules form a capsule around capillary tufts, allowing some blood filtration. The mesonephros functions as an interim kidney during the first trimester. Although most of these tubules eventually degenerate, components of the mesonephros contribute to the male reproductive system.
Formation of the Permanent Kidney
The permanent kidney, known as the metanephros, begins to develop during the fifth week of the embryonic period in the sacral region. Its formation relies on a reciprocal interaction between two main components: the ureteric bud and the metanephric mesenchyme. The ureteric bud is an outgrowth of the mesonephric duct, which grows into the metanephric mesenchyme. This interaction involves signaling where the mesenchyme induces the ureteric bud to grow and branch extensively, forming the collecting duct system of the kidney, including the ureter, renal pelvis, major and minor calyces, and collecting tubules.
In turn, the tips of the branching ureteric bud induce the metanephric mesenchyme cells to condense around them and undergo a process called mesenchymal-to-epithelial transition. These mesenchymal cells then form epithelial structures that differentiate into the functional filtering units of the kidney, called nephrons. Each nephron begins as a renal vesicle and develops further. This process, called nephrogenesis, continues until late gestation, when the full complement of nephrons, typically around one million per kidney, is formed.
Within each developing nephron, the glomerulus forms as a capillary tuft that receives blood supply from an afferent arteriole. Podocyte precursors induce the migration of endothelial cells to form these glomerular capillaries. The glomerulus is enveloped by Bowman’s capsule, a double-walled cup that marks the beginning of the renal tubule. The renal tubule then differentiates into distinct segments, including the proximal convoluted tubule, the loop of Henle, and the distal convoluted tubule.
Developmental Variations and Congenital Conditions
Disruptions during kidney development can lead to various congenital anomalies of the kidney and urinary tract (CAKUT). These conditions can range from mild to severe, sometimes leading to renal failure in children. Renal agenesis is the complete absence of one or both kidneys. This occurs when the ureteric bud fails to form or degenerates early, preventing kidney development. Bilateral renal agenesis results in Potter sequence, characterized by severe lung underdevelopment and distinctive facial and limb deformities, and is typically incompatible with life.
Renal hypoplasia is when kidneys are abnormally small and have a reduced number of nephrons, even though their overall structure remains normal. This condition arises from reduced branching morphogenesis of the ureteric bud. Duplicated collecting systems occur when there are two ureters draining a single kidney, often resulting from an early division of the ureteric bud. The extent of the duplication depends on when this division occurs during development.
A horseshoe kidney is a fusion anomaly where the lower poles of the kidneys join across the midline, forming a U-shape. This fusion can prevent the kidneys from ascending to their normal position in the abdomen, often trapping them under the inferior mesenteric artery. While often asymptomatic, a horseshoe kidney can increase the risk of urinary tract infections, kidney stones, and hydronephrosis. Polycystic kidney disease (PKD) involves the formation of multiple fluid-filled cysts within the kidneys. PKD is a genetically inherited condition, with autosomal dominant PKD typically manifesting in adulthood and autosomal recessive PKD often presenting in infancy with enlarged, cyst-filled kidneys and severe renal dysfunction.