Table of Contents
- Kidney Development: Development over Three Generations of Structures
- Ascension of the Kidney
- Development of the Ureters
- Blood Supply to the Kidneys
- Development of the Urinary Bladder
- Development of the Urethra
- Normal and Abnormal Amniotic Fluid Circulation
- Pathology of the Kidneys and the Efferent Urinary Tract
- Exam Questions relating to Kidney Development
Kidney Development: Development over Three Generations of Structures
During their development, the kidneys form with parts of three different structures, called:
What all three structures have in common is that they all form from the intermediate mesoderm of the embryo. In the cervical area, this mesoderm is segmented, thereafter caudally forming the uniform nephrogenic cord, whose epithelium protrudes as the kidney ridge next to the gonadal ridge. Together, these two ridges form the urogenital fold.
In the third week, the pronephros forms in the cervical nephrotomes. It is a functionless, segmented structure made out of a duct from which a series of tubules take off aiming toward the midline of the embryo, one on each side. Pronephros does not go further than a rudimentary state and regresses without ever having produced urine. The two pronephric ducts (ducti pronephrici) that form at the lateral edge of the intermediate mesoderm remain in part.
Immediately caudal to the pronephros, that is in the thoracic and lumbar area,a tubular structure called mesonephros begins to form from the end of the fourth week, while the pronephros is still regressing. This is an elongated organ, which is no longer segmented, and has renal corpuscles or nephrons, which, for a short period, are able to produce urine.
The mesonephros is connected to the pronephric duct via the mesonephric duct. Caudally, it continues as the mesonephric duct (ductus mesonephricus, or Wolffian duct). It connects to the cloaca. The Wolffian duct plays an essential role in the sexual development of men. The functionless remains of the mesonephric anlage are also found in women.
The mesonephros is functional for roughly four weeks, then regresses. A few tubules remain, later becoming the efferent ducts of the epididymis in men (see Cryptorchidism (Undescended Testicle) — Diagnosis and Treatment). This shows how closely this aspect of development is connected to sexual development, such that it is often referred to as urogenital development.
The development of the metanephros, which constitutes the final urine-producing organ, is more complex. It develops from the fifth week, caudal to the mesonephros, in the lumbar area, from projections originating from the mesonephric tubule near its attachment to the cloaca called the ureteric buds. At this time, the mesonephros is still regressing. Initially the metanephros primarily functions for fluid and pressure balance rather than metabolism, since in embryos this function is performed by the placenta.
The ureteric bud, also called the metanephrogenic diverticulum, grows posteriorly and towards the head of the embryo. The elongated stalk of the ureteric bud, called the metanephric duct, later forms the ureter. As the cranial end of the bud extends into the intermediate mesoderm, it undergoes a series of branchings to form the collecting duct system of the kidney. It also forms the major and minor calyces and the renal pelvis.
The portion of undifferentiated intermediate mesoderm in contact with the tips of the branching ureteric bud is known as the metanephrogenic blastema. Signals released from the ureteric bud induce the differentiation of the metanephrogenic blastema into the renal tubules. As the renal tubules grow, they come into contact and join with connecting tubules of the collecting duct system, forming a continuous passage for flow from the renal tubule to the collecting duct. Simultaneously, precursors of vascular endothelial cells begin to take their position at the tips of the renal tubules. These cells differentiate into the cells of the definitive glomerulus.
The following form out of the stem of the ureteric bud which has sprouted, by means of widening and branching:
- the ureter
- the renal pelvis
- the five major calyces
- the minor calyces
- the collecting ducts
The following structures form out of the metanephrogenic blastema:
- Bowman’s capsule
- the proximal and distal tubules
- the Loop of Henle
At the end of the collecting ducts, mesenchymal cells condense to the metanephric vesicle in the metanephrogenic blastema. This forms metanephric tubules, to which capillary loops attach. The epithelium at the capillaries alters to become podocytes, the visceral sheet of Bowman’s capsule, the overlying cohesive epithelium covering the parietal sheet of the podocytes.
The superior section of the metanephric vesicle further elongates to connect to the collecting ducts. Thus, the nephron, the smallest unit of the kidney, is completed. From the fourth month, the definitive kidney, a description for the completed metanephros, produces urine, which is directed into the amniotic cavity of the embryo, where it is in turn swallowed by the embryo.
Ascension of the Kidney
In contrast to the more superficially located mesonephros, the metanephros is, from the outset, located in the retroperitoneum. Growth of the embryo in the lumbar and sacral area is accompanied by the ascension of the kidney; the kidneys are moved into the abdomen, underneath the adrenal glands. The left kidney completes the ascension at the level of Th11-L2, the right one slightly lower at the level of Th12-L2/3.
The ureter must grow in length during the ascension since it is connected to both the kidneys and the urinary bladder. This movement is completed at about the ninth week. Sometimes the process is referred to as a relative ascension. This means that only an apparent movement into the abdomen occurs since the embryo just grows away from the kidneys, underneath them.
Development of the Ureters
In the fifth week, the ureteric bud arises from the mesonephric duct, close to where the mesonephric duct attaches to the cloaca. This grows into the metanephrogenic blastema in a dorso-cranial direction. There it branches into additional structures. The stem of the ureteric bud is then called the ureter.
In the course of the development of the urinary bladder, there is a widening of the Wolffian duct as far as the separation of the ureter so that, eventually, the ureter is directly connected to the bladder. During the ascension of the kidneys, the ureters are stretched not only in length, but also laterally so that they discharge into the urinary bladder inferiorly and laterally.
Blood Supply to the Kidneys
The kidneys are initially supplied by the common iliac arteries, in keeping with their location in the pelvis. Upon their ascension, new vessels form on the respective level of the aorta. These vessels normally disappear completely since they become unnecessary upon further ascension. The final renal arteries form when the kidneys arrive at their destination underneath the adrenal glands.
Development of the Urinary Bladder
In embryonic development, the urinary bladder is formed out of the cloaca, which constitutes the caudal end of the hindgut. At first, both the urogenital tract and the intestine end in the cloaca. It originates from endoderm and is connected to the navel via the allantois in a ventro-cranial direction. The so-called cloacal membrane, which originates from both the ectoderm and the endoderm, seals the cloaca.
From the fourth week of development, an epithelial transversal fold, with the adjacent mesenchyme, grows from a cranial direction towards the cloacal membrane: the urorectal septum. This septum separates the cloaca into two parts, the dorsal anorectal canal and the ventral urogenital sinus. The part between the two sections of the cloacal membrane is referred to as the perineum.
The urogenital sinus can be divided into three sections or levels:
- the cranial vesicular part
- the medial pelvic part
- the caudal phallic part
The cranial vesicular part merges with the allantois, which later obliterates and takes no part in the formation of the bladder, along with the urachus. In adults, the urachus remains as the median umbilical ligament. The two mesonephric ducts lead to the cranial part of the urogenital sinus and then widen so that the ureteric buds and subsequently the ureters lead directly into the urinary bladder.
The bladder trigone is thereby formed. It constitutes the connective tissue element of the bladder, which develops out of the widened mesonephric ducts and is located between the openings of the two ureters and the mesonephric ducts, which almost fuse caudally. This section therefore originates from the mesoderm. However, during its further development it is also covered by endodermal epithelium.
Development of the Urethra
In a female fetus, the middle part, that is the pelvic part, forms the complete urethra. In a male fetus, it only accounts for the proximal parts of the urethra, i.e. the intramural part, the prostatic part, and the membranous part of the male urethra as far as the seminal colliculus.
In a female fetus the vaginal vestibule develops from the caudal phallic part. It later grows together with the utero-vaginal canal. In male fetuses, this section of the urogenital sinus forms the spongy part of the urethra. The external genitals develop from the folds attached to the urogenital sinus.
The whole female urethra therefore originates from the endoderm. The male urethra also mainly is of endodermal origin. However, it has a small part in the glans penis, which is ectodermal and which grows together with the spongy part out of the urogenital sinus.
Normal and Abnormal Amniotic Fluid Circulation
Amniotic fluid is produced by the cells (amnioblasts) lining the amniotic cavity. The embryo and fetus will swallow this fluid and a corresponding amount of fluid is excreted via the kidneys. This is NOT urine! True waste products are handled by the mother via the placenta.
If there is something wrong with the swallowing process (e.g. blockage of the gut at some level) then excess amniotic fluid builds up (polyhydramnios) (> 25 cm total depth on 4 ultrasound measurements). If there is something wrong with the fluid excretion (blocked urethra, kidneys not functioning), there will be a deficiency of amniotic fluid (oligohydramnios) (< 5 cm total depth on 4 ultrasound measurements). These measurements are the “Amniotic Fluid Index”, or AFI.
About 8 % of women have oligohydramnios, which may resolve spontaneously.
- Monitor baby — deliver early?
- Add saline?
About 2 % of women have polyhydramnios, which leads to maternal discomfort/ breathing. Amiocentesis may help.
Pathology of the Kidneys and the Efferent Urinary Tract
Malformations in development can, in principle, occur at each stage. 3-4 % of newborns show abnormalities in kidney or ureter development. Higher familial incidences are observable. Such incidences can often be found prior to birth via ultrasound.
Malformations of the kidney
Cystic Kidney Diseases
The cystic kidney diseases can be divided into two types:
- Polycystic kidney disease, Potter type I
- Multicystic dysplastic kidney, Potter type IIA
In both diseases the occurrence of cysts impairs the development of renal tissue. Polycystic kidney disease is inherited as an autosomal recessive trait, and is indicative of poor progress and poorer postnatal chances of survival. A multicystic dysplastic kidney is often limited to one side. It generally contains fewer cysts so that the chance of survival is better.
Renal agenesis signifies the absence of one or both kidneys. This can either be traced back to an absent metanephrogenic blastema or to a non-developed ureteric bud. While the absence of one kidney is not problematic as the other kidney hypertrophies to compensate, the absence of both kidneys is not compatible with postnatal life.
Before birth, renal agenesis on both sides presents itself via oligohydramnios, a lack of amniotic fluid. The reason for this is that too little or no urine is excreted into the amniotic cavity. If the electrolyte balance of the fetus has not been disrupted – as the exchange occurs via the placenta – children with double-sided agenesis die shortly after birth.
Renal aplasia means the incorrect development of one or both kidneys. As with renal agenesis, a double-sided occurrence is not compatible with life. Incorrect anlage of metanephrogenic blastema or mesonephric ducts can be the cause of this malformation. Inoperable cysts or tubules often develop.
Double kidneys develop from either complete division of the ureteric bud or a double anlage. The development of double kidneys is rare compared to the double ureter. In this case, the ureter of the superior kidney ends caudal-medially, and the ureter of the inferior kidney anlage ends cranially in the urinary bladder.
Abnormalities in kidney location often develop when there has been incorrect ascension. This can either affect one or both kidneys. Usually, patients with dystopic kidneys are asymptomatic and are usually not treated. Examples of dystopic kidneys are
- pelvic kidneys: ascension halts
- clump kidneys: disc-shaped fusion of both kidneys
- horseshoe kidneys: fusion of both kidneys at their poles
- crossed kidney ectopia: a kidney reaches to the other side (with or without fusion)
Malformations of the Ureter
Ureter Duplex and Ureter Fissus
A double ureter forms by division of the ureteric bud or a double anlage. In this case the ureter fissus is only partially split. This can result in a divided or double kidney with only one junction to the urinary bladder. The ureter duplex is completely separated. This usually leads to a double kidney with two separated junctions to the urinary bladder.
An atypical junction to the efferent urinary system is referred to as an ectopic ureter. This often results in incontinence since the urinary bladder is only sealed by sphincters. In boys the ureters often open into the prostatic urethra or the neck of the urinary bladder. In girls they open in the vagina or the vaginal vestibule. The cause is an incorrect alignment of the ureter in relation to the Wolffian duct.
Malformations of the Bladder
If the urogenital septum fails to separate the cloaca, or separates it only partially, a so-called persistent cloaca results. In this case the intestinal and urinary tracts both end in a common canal. The genital tract is often also included.
Bladder exstrophy can be traced back to failed migration of mesenchymal cells into the space between the abdominal wall and the bladder wall, resulting in absence of the muscular layer. The posterior wall of the bladder and the openings of the ureters are exposed. Incontinence occurs due to protrusion of the wall of the bladder into the anterior abdominal wall.
Malformations of the Urethra
Hypospadias and Epispadias
Hypospadias describes the formation of a ventral fissure of the urethra, whereas epispadias means a dorsal fissure. Incorrect fusion of the urethral folds is the cause for this. Both variations result in an incorrect junction of the external urethral meatus and are treated via surgery. In both cases boys are affected more frequently than girls.
Incorrect Regression of the Urachus
If the urachus does not completely regress during embryonic development, small hollow cavities, which are referred to as urachal cysts, remain in the previously extant duct. Clinically, they normally are rather discrete. However, they can become inflamed and in this case they must be treated by surgery.
If the urachus does not close completely, urine can further pass through the duct. Distinctions are drawn between an inner urachal fistula containing an opening in the section close to the bladder, an outer urachal fistula containing an opening at the navel, and a complete urachal fistula containing a passage from bladder to the navel. The final variation permits urine to exit the navel.
Exam Questions relating to Kidney Development
The answers can be found below the references.
1. Which statement is true with respect to the development of the kidneys?
- The pronephros performs the same task as the meso- and metanephros.
- The mesonephros is the only segmented structure.
- The metanephros is the final urine-producing organ.
- The collecting ducts consist of minor calyces.
- The pronephros is non-functional and completely regresses.
2. Which statement is true concerning the development of the urinary bladder?
- The urinary bladder originates solely from endoderm.
- In the fetus, the urinary bladder is connected to the navel via the allantois.
- The urorectal septum separates the urogenital sinus.
- The bladder trigone is bordered by the urachus.
- The urinary bladder consists of the phallic part of the urogenital sinus.
3. The relative ascension of the kidneys indicates
- An incomplete ascension of the kidneys.
- A relatively marginal ascension of the kidneys compared to the ureter.
- An actual descending of the kidneys compared to the other organs of the abdomen.
- An ascension of the kidneys due to the embryonic growth caudal of the kidneys.
- The ascension of one and the descending of the other kidney.