Development of the renal system

Definitions & Key takeaways

The renal system starts to form at about week 4 of gestation from a portion of the urogenital ridge called the nephrogenic cord. The nephrogenic cord gives rise to three overlapping developmental stages: the pronephros, the mesonephros, and the metanephros. Pronephros consists of an early and nonfunctional system, which regresses by week 4. Next is the mesonephros, which functions as a primitive excretory system in the embryo. Most tubules regress by week eight and are replaced by the metanephros. Metanephros give rise to actual kidneys, which appear at around week five, and become mature enough to secrete urine around week ten.

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The renal system starts developing during week 4 of intrauterine life. At that point, the embryo is made up of three primitive germ layers: the ectoderm, the mesoderm and the endoderm.
The mesoderm also has three parts: the paraxial mesoderm, flanking the embryo’s future vertebral column, the intermediate mesoderm which is just lateral to it, and the lateral plate mesoderm which is the most lateral of all.
The intermediate mesoderm on either side of the embryo condenses to form a cylindrical structure called the urogenital ridge.
This ridge runs parallel to the embryo’s future vertebral column, and it gives rise to both the urinary and the genital systems.
The portion of the urogenital ridge called the nephrogenic cord is what develops into the urinary structures«. Now, during the development of the urinary system, there are three sets of structures that emerge from the nephrogenic cord, and they form in a cranio-caudal fashion - or from the head towards the tail of the embryo.
The first of them is the pronephros, and it appears at the beginning of week 4, in the neck region of the embryo. The pronephros consists of the pronephric duct and the nephrotomes in front of it.
The pronephric duct is basically a pipe that runs down the length of the nephrogenic cord, and the nephrotomes are small chunks of tissue that break off of the nephrogenic cord.
However, the pronephros don’t produce urine, and regress by the end of week 4. Before the pronephros completely disappears, a second set of structures called the mesonephros appears in the thoracic and upper lumbar region of the nephrogenic cord.
The mesonephros has a mesonephric duct and mesonephric tubules in front of it. The mesonephric duct develops off of the pronephric duct, making it longer so that it reaches all the way to the cloaca, which is the last part of the primitive digestive tract.
So for a short while, the urinary and digestive system share a common exit. Just like the nephrotomes, the mesonephric tubules break off as chunks of tissue from the nephrogenic cord.
The mesonephric tubules are hollow, S-shaped tubes. On one end, they connect to the mesonephric duct, and at the other end, the tubule forms a cup shape called a Bowman’s capsule around a clump of capillaries called a glomerulus.
This primitive structure extracts fluid from the capillaries and the fluid flows down the duct forming urine. The urine is drained through the mesonephric duct into the cloaca.
This system is in place until week 10, when the permanent kidneys take over and the mesonephros regresses. Around week 5, the metanephros develops, and it forms the permanent kidneys - so for a couple of weeks, the metanephros and mesonephros coexist.
The metanephros form in the pelvic region. First, intermediate mesoderm near the mesonephric duct differentiates into metanephric mesoderm, sometimes called the metanephric blastema.
The metanephric mesoderm produces growth factors that travel to the mesonephric duct, and in response it sprouts a small bud called the ureteric bud, which is connected to the mesonephric duct through the ureteric stalk.
Over time, the ureteric bud lengthens and it secretes growth factors that causes the metanephric mesoderm to grow. This is called reciprocal induction, because the metanephric mesoderm and the ureteric bud promote each other’s growth.
Eventually, the ureteric bud reaches the metanephric mesoderm and grows into it, like two lovers running (albeit very slowly) towards one another.
The metanephric mesoderm surrounds the end of the ureteric bud, leaving just the ureteric stalk uncovered. The ureteric stalk lengthens and forms the ureter during about week 6.
The ureteric bud that’s within the metanephric mesoderm divides in half to form the renal pelvis during weeks 7 and 8, then each half divides again to form two future major calyces.
This division continues until the the major calyces, the minor calyces, and finally millions of collecting tubules have formed.
The cells in the collecting tubules signal the surrounding metanephric mesoderm that the collecting system is in place, and it’s time for the nephrons to form.
The nephrons are the basic functional unit of the kidney, and start forming during week 8 - so let’s zoom in and see how that happens.
Each newly formed collecting tubule is surrounded by a cap of metanephric mesoderm. Cells in the collecting tubules which come from the ureteric bud, signal the nearby metanephric mesoderm to form round cell clusters called metanephric vesicles.
The vesicles elongate and bend into an S shaped tube and are similar to the mesonephric tubules. One end of the tube connects with the collecting tubules and that part becomes the distal convoluted tubule.
The other end of the tube forms the proximal convoluted tubule. The proximal convoluted tubule forms a little cup called Bowman’s capsule for a clump of capillaries that come in as branches from the aorta and form the glomerulus.
Now, the portion in between the distal and proximal convoluted tubules lengthens and gives rise to the loop of Henle. Around week 10, these nephrons start producing urine, and at that point, the metanephros takes over as permanent kidney.
Now, as the permanent kidneys develop, they move up from the pelvis to reach their adult position. Initially, the kidneys are nourished by internal iliac arteries that branch off from the aorta, but as the kidneys ascend, the aorta forms branches at higher and higher levels to send them blood.
When the kidneys get to their final home in the upper abdomen, the renal arteries forms, and the lower branches degenerate.
Rewinding a bit, while the kidneys are forming, the bladder and urethra are developing as well. The process begins in week 4, when a wall of tissue forms in the cloaca and it’s called the urorectal septum.
The urorectal septum splits the cloaca into a posterior anal canal for the digestive tract, and an anterior urogenital sinus for genital and urinary structures.
The top portion of the urogenital sinus stretches out to form the primitive bladder. Now, remember that the ureters develop from the ureteric stalk, and they open into the mesonephric ducts, which drain urine into the bladder.
During weeks 5 and 6, the mesonephric ducts get slowly absorbed into the bladder, and form the smooth part of the bladder wall called the vesical trigone.
The vesical trigone is a triangular region that contains the openings of the ureters, as well as the opening of the urethra.
The middle portion of the urogenital sinus forms the urethra in females and the prostatic and membranous parts of the urethra in males.
Finally, the bottom portion of the urogenital sinus grows towards the genital tubercle, which forms the clitoris in females and the penis in males.
All right, as a quick recap: the nephrogenic cord, which is part of the urogenital ridge, gives rise to three sets of structures form in intrauterine life - the pronephros, the mesonephros, and the metanephros.
The metanephros are the permanent kidneys, and they form from the metanephric mesoderm, which forms the nephrons, as well as from the ureteric bud, which forms the collecting system.
The metanephric mesoderm forms a small part of the bladder, but the urogenital sinus is responsible for most of the bladder and the entire urethra starting with the fourth week.
The permanent urinary system is mature enough to secrete urine starting around week 10 of intrauterine life.