How does kidney develop during gestation ?

The students of renal pathology, medicine, nephrology and urology would always like to imbibe knowledge about the origin and development of kidney to understand the pathogenesis of developmental kidney diseases. The urogenital system is derived and developed from the intermediate mesoderm and the primitive urogenital sinus of the cloaca. The ureteral bud (UB) develops from the Wolffian duct (WD) at approximately 28 days of gestation. The ureteral bud (UB) initiates the epithelialization/tubulogenesis of the metanephric mesenchyme (MM) while itself undergoes branching to form and adult kidney. Much knowledge about the development of kidney could be gathered from the experimental studies using mouse embryo. In the mouse the ureteral bud (UB) invaginates from the caudal end of the Wolffian duct (WD) and grows out into the adjacent metanephric mesenchyme cells.

The metanephric mesenchyme cells comprise of tubule precursors, endothelial precursors and stromal cells. These loose metanephric mesenchyme cells aggregate to form "pre tubular aggregate" which undergoes structural change to form a 'tear-drop' like structure called renal vesicle (RV). The renal vesicle rapidly undergoes mesenchymal-epithelial transformation (MET) to form a comma-shaped structure. The comma-shaped structure formed by the mesenchymal-epithelial transformation of RV undergoes series of tightly controlled transformations and form a very complex S-shaped body. The lower part of the "S" (of S-shaped body) gives rise to podocytes and Bowman's capsule. The upper part of the "S" (of S-shaped body) forms the distal convoluted tubule of the nephron. The middle segment of the "S" (of S-shaped body) gives rise to the proximal convoluted tubule and the loop of Henle of the nephron. Each tip of the ureteral bud gives rise to a nephron. After 20-22 weeks of gestation in humans, the ureteral bud stops branching but the nephron induction continues for other 8 to10 weeks, leading to arcade formation wherein each tip of the ureteral bud has 9-11 nephrons attached to it. The arcade formation is considered as the last step of the nephron induction in humans. However, in mice the process of nephron induction continues for about two weeks after birth. The mouse kidney has single papilla and carries around 35,000 nephrons/kidney. Human kidneys roughly contain 6x10⁵ to 1.1x10⁶ nephrons/kidney.

The knowledge of developmental stages of kidney is important to understand the pathogenesis of developmental cystic kidney diseases like renal agenesis (no kidney developed), renal hypoplasia (under developed kidneys) and renal dysplasia (abnormally developed kidneys). Renal hypoplasia (reduction in total number of nephrons), renal dysplasia (abnormally developed kidney due to failure of UB to induce formation of nephrons) and segmental hypoplasia are the major developmental cystic kidney diseases. Simple hypoplasia leads to very small sized kidney called miniature kidney. Miniature kidney would represent reduction in renal calyces with glomerular disarray and reduction of tubules, medulla & cortex. Segmental hypoplasia presents during the late childhood with renal insufficiency associated with hypertension and recurrent urinary tract infection (UTI). Patients with segmental hypoplasia have small sized kidney (s) with a transverse groove on the capsular surface at the upper pole, overlying an area of marked parenchymal thinning. Areas of segmental hypoplasia represented by scarred zones with no glomeruli, atrophic tubules and thick walled blood vessels could be revealed under light microscopy of histological sections.