Metanephros

The metanephros is the third and definitive embryonic renal system. It gives rise to the permanent kidneys and begins developing after the pronephric and mesonephric systems have appeared. Metanephric development depends on coordinated interactions between two embryonic components: the ureteric bud and the metanephric mesenchyme.

The ureteric bud produces the collecting portion of the kidney, including the ureter, renal pelvis, calyces, and collecting ducts. The metanephric mesenchyme produces the nephrons. Reciprocal signaling between these tissues is essential for normal kidney formation.

Three Embryonic Renal Systems

Human renal development occurs through three sequential systems derived primarily from intermediate mesoderm.

1. Pronephros, the earliest and nonfunctional system
2. Mesonephros, the temporary functional renal system
3. Metanephros, the definitive renal system

Beginning of Metanephric Development

The metanephros begins to develop during approximately the fifth week of embryonic development.

At this stage, the permanent kidneys are located in the caudal part of the embryo, within the pelvic region.

Embryological Components

Formation of the metanephric kidney requires two major developmental components.

• Ureteric bud, an epithelial outgrowth from the mesonephric duct
• Metanephric mesenchyme, also called the metanephric blastema

Neither component can form a normal kidney independently. Each induces developmental changes in the other.

Intermediate Mesoderm

The metanephric mesenchyme ultimately derives from intermediate mesoderm.

Intermediate mesoderm forms the nephrogenic tissue from which successive urinary structures develop along the posterior body wall.

Metanephric Mesenchyme

The metanephric mesenchyme is a specialized mass of nephrogenic tissue located in the caudal region of the embryo.

It surrounds the distal end of the invading ureteric bud and gives rise to the excretory units of the permanent kidney.

Ureteric Bud

The ureteric bud arises from the caudal portion of the mesonephric duct near its connection with the developing cloaca.

It grows dorsocranially into the metanephric mesenchyme and begins a complex program of repeated branching.

Induction of Kidney Development

Normal kidney formation depends on reciprocal induction between the ureteric bud and metanephric mesenchyme.

The mesenchyme promotes growth and branching of the ureteric bud, while signals from the ureteric epithelium induce adjacent mesenchymal cells to differentiate into nephron-forming epithelial structures.

Branching Morphogenesis

After entering the metanephric mesenchyme, the ureteric bud undergoes repeated branching.

This branching process establishes the collecting system and provides the structural framework around which nephrons develop.

Ureteric Bud Derivatives

The ureteric bud forms the collecting portion of the permanent urinary system.

• Ureter
• Renal pelvis
• Major calyces
• Minor calyces
• Collecting ducts
• Collecting tubules

Formation of the Ureter

The proximal stalk of the ureteric bud elongates and becomes the ureter.

As the kidneys change position during development, the ureters elongate while maintaining their connections with the urinary bladder.

Formation of the Renal Pelvis

The expanded cranial portion of the ureteric bud contributes to formation of the renal pelvis.

Further branching from this region establishes progressively smaller components of the collecting system.

Major Calyces

Early branches of the ureteric bud enlarge and contribute to formation of the major calyces.

These structures ultimately receive urine from groups of minor calyces.

Minor Calyces

Continued branching produces additional generations of collecting structures that contribute to the minor calyces.

Each minor calyx eventually receives urine from renal papillae.

Collecting Ducts

Repeated branching of the ureteric bud produces the extensive system of collecting ducts.

These ducts receive urine from developing nephrons and convey it toward the calyces and renal pelvis.

Metanephric Mesenchyme Derivatives

The metanephric mesenchyme forms the nephron components of the permanent kidney.

• Bowman's capsule
• Proximal convoluted tubule
• Loop of Henle
• Distal convoluted tubule

Nephron Formation

Signals from terminal branches of the collecting system induce nearby metanephric mesenchymal cells to condense.

These condensed cells undergo a mesenchymal-to-epithelial transition and form epithelial structures that develop into nephrons.

Renal Vesicle

The induced mesenchymal cells initially organize into a small epithelial structure called the renal vesicle.

The renal vesicle represents an early stage in nephron formation.

Comma-Shaped Body

The renal vesicle elongates and changes shape to form a comma-shaped body.

This structure undergoes further growth and differentiation as the developing nephron becomes increasingly complex.

S-Shaped Body

The comma-shaped body develops into an S-shaped body.

Different portions of this structure subsequently differentiate into the renal corpuscle and tubular components of the nephron.

Formation of the Renal Corpuscle

Capillaries grow into one end of the S-shaped nephron precursor.

The epithelial cells surrounding these capillaries differentiate to form the visceral and parietal components of Bowman's capsule, establishing the renal corpuscle.

Glomerulus

The capillary tuft within the developing renal corpuscle becomes the glomerulus.

It provides the vascular component of the filtration apparatus of the mature nephron.

Bowman's Capsule

Bowman's capsule develops from the nephron-forming metanephric tissue rather than from the ureteric bud.

Its visceral layer becomes closely associated with glomerular capillaries, while its parietal layer forms the outer wall of the renal corpuscle.

Proximal Convoluted Tubule

Part of the developing nephron elongates and differentiates into the proximal convoluted tubule.

This segment later becomes specialized for extensive reabsorption from the glomerular filtrate.

Loop of Henle

Further elongation of the developing nephron produces the loop of Henle.

The degree of elongation contributes to the organization of nephrons within the developing renal cortex and medulla.

Distal Convoluted Tubule

The distal portion of the nephron differentiates into the distal convoluted tubule.

It establishes continuity with a collecting tubule derived from the ureteric bud.

Connection Between Nephron and Collecting System

For the kidney to function, each developing nephron must establish a patent connection with the collecting system.

The distal end of the nephron joins a collecting tubule, creating a continuous pathway from the renal corpuscle to the renal pelvis.

Dual Embryological Origin of the Kidney

Embryonic Source	Major Derivatives
Ureteric bud	Ureter, renal pelvis, major calyces, minor calyces, collecting ducts
Metanephric mesenchyme	Bowman's capsule, proximal tubule, loop of Henle, distal tubule

Beginning of Renal Function

The developing metanephric kidneys begin producing urine during fetal life, after nephron and collecting-system connections become sufficiently developed.

Urine passes through the ureters into the developing urinary bladder and subsequently contributes to the amniotic fluid.

Fetal Renal Function

The fetal kidneys produce urine, but the placenta remains the principal organ responsible for removal of fetal metabolic waste products.

Fetal urine is particularly important for maintaining the volume of amniotic fluid during later pregnancy.

Renal Ascent

The metanephric kidneys initially develop within the pelvic region.

As the embryo grows, they appear to ascend into the posterior abdominal region.

Mechanism of Renal Ascent

Renal ascent is primarily an apparent movement produced by differential growth of the embryonic body rather than active migration of the kidneys over a long distance.

The kidneys gradually occupy increasingly superior positions as the caudal body develops.

Final Renal Position

The kidneys eventually reach their definitive retroperitoneal positions on the posterior abdominal wall.

The right kidney normally lies slightly lower than the left in the mature body.

Renal Rotation

During ascent, the metanephric kidneys also undergo rotation.

The hila initially face predominantly anteriorly and gradually rotate toward the midline.

Final Hilum Orientation

Following normal rotation, the renal hila face predominantly medially.

Failure or alteration of this rotational process can produce renal malrotation.

Changing Arterial Supply

The blood supply of the developing kidneys changes repeatedly during renal ascent.

At lower levels, the kidneys receive vessels from nearby arteries. As they ascend, new arterial branches arise from progressively higher levels while many lower vessels regress.

Definitive Renal Arteries

The mature renal arteries normally arise from the abdominal aorta.

Persistence of earlier embryonic vessels can produce accessory or aberrant renal arteries.

Accessory Renal Arteries

Accessory renal arteries are common anatomical variations and reflect persistence of embryonic vessels that normally regress during renal ascent.

They may enter the renal hilum or supply a renal pole directly.

Renal Lobulation

The developing fetal kidney has a distinctly lobulated external appearance.

This fetal lobulation reflects the organization of developing renal tissue into multiple lobes.

Fetal Lobulation

Renal lobulation normally becomes less conspicuous as the kidney grows.

In some adults, shallow grooves persist on the renal surface as persistent fetal lobulation, which is generally an anatomical variant rather than disease.

Nephrogenesis

Nephrogenesis is the process by which new nephrons are formed from metanephric mesenchyme.

Successive generations of nephrons develop as branching collecting ducts continue to induce surrounding nephrogenic tissue.

Completion of Nephrogenesis

Nephron formation occurs during fetal development and is essentially completed before or around the time of birth.

After nephrogenesis ends, subsequent kidney growth occurs mainly through enlargement and maturation of existing nephrons rather than formation of large numbers of new nephrons.

Nephron Number

The final number of nephrons varies among individuals.

Normal nephron endowment depends on appropriate fetal growth, adequate developmental signaling, and successful completion of metanephric development.

Pronephros, Mesonephros and Metanephros

Feature	Pronephros	Mesonephros	Metanephros
Sequence	First	Second	Third
Human renal function	Nonfunctional	Temporary	Permanent
Persistence	Regresses	Mostly regresses	Forms definitive kidneys
Major significance	Early developmental system	Temporary kidney and reproductive derivatives	Permanent renal system

Relationship to the Mesonephric Duct

The metanephros has an important developmental connection with the mesonephric system because the ureteric bud arises from the mesonephric duct.

Thus, a structure associated with the temporary mesonephric kidney provides the epithelial precursor of the permanent collecting system.

Reciprocal Induction

Reciprocal signaling is central to metanephric development.

Without appropriate signaling from the metanephric mesenchyme, the ureteric bud may fail to grow or branch normally. Without signals from the ureteric bud, the metanephric mesenchyme does not undergo normal nephron differentiation.

Failure of Ureteric Bud Development

Failure of the ureteric bud to form, reach the metanephric mesenchyme, or induce it appropriately can prevent development of the definitive kidney.

This mechanism contributes to forms of renal agenesis.

Renal Agenesis

Renal agenesis is congenital absence of renal tissue resulting from failure of normal kidney development.

It may be unilateral or bilateral, with very different clinical consequences.

Unilateral Renal Agenesis

When one metanephric kidney fails to develop, the opposite kidney can undergo compensatory enlargement and may provide sufficient renal function.

The anomaly may therefore remain clinically silent for a prolonged period.

Bilateral Renal Agenesis

Failure of both permanent kidneys to develop causes severe reduction or absence of fetal urine production.

This profoundly affects amniotic fluid volume and fetal development.

Oligohydramnios

Because fetal urine contributes substantially to amniotic fluid during later pregnancy, severe impairment of fetal renal function can produce oligohydramnios.

Markedly reduced amniotic fluid can interfere with normal fetal development, particularly pulmonary development.

Ectopic Kidney

An ectopic kidney develops when the metanephric kidney does not reach its normal definitive position.

A pelvic kidney results when renal ascent is markedly limited.

Horseshoe Kidney

A horseshoe kidney forms when the developing kidneys become fused, usually at their lower poles.

The fused kidney generally remains lower than normal because its ascent is restricted.

Renal Malrotation

Abnormal rotation during ascent can leave the renal hilum facing anteriorly or in another atypical direction.

Malrotation frequently accompanies renal ectopia and fusion anomalies.

Duplicated Collecting System

Abnormal branching or duplication of the ureteric bud can produce duplicated ureters or duplex collecting systems.

The anatomy depends on whether a single bud divides prematurely or more than one ureteric bud develops.

Congenital Abnormalities and Developmental Mechanisms

Developmental Disturbance	Possible Result
Failure of ureteric bud induction	Renal agenesis or severe dysplasia
Abnormal renal ascent	Ectopic kidney
Fusion of developing kidneys	Horseshoe kidney
Abnormal rotation	Renal malrotation
Abnormal ureteric bud branching	Duplicated collecting system
Persistence of embryonic arteries	Accessory renal arteries

Developmental Sequence

1. Intermediate mesoderm forms nephrogenic tissue.
2. The pronephros develops and regresses.
3. The mesonephros develops and functions temporarily.
4. The ureteric bud arises from the caudal mesonephric duct.
5. The bud grows into the metanephric mesenchyme.
6. Reciprocal induction begins between the two tissues.
7. The ureteric bud undergoes repeated branching.
8. Metanephric mesenchyme forms renal vesicles.
9. Renal vesicles develop into comma-shaped and S-shaped bodies.
10. Capillaries invade developing renal corpuscles.
11. Nephrons connect with collecting tubules.
12. The kidneys begin producing urine during fetal development.
13. The kidneys ascend from the pelvis toward the lumbar region.
14. Renal rotation changes the orientation of the hila.
15. The renal vascular supply changes during ascent.

Key Embryological Features

• The metanephros is the third embryonic renal system.
• It forms the permanent kidneys.
• Development begins during approximately the fifth embryonic week.
• The permanent kidney has a dual embryological origin.
• The ureteric bud arises from the mesonephric duct.
• The ureteric bud forms the collecting system.
• The metanephric mesenchyme forms the nephrons.
• Reciprocal induction between the two tissues is essential.
• Renal vesicles develop into comma-shaped and S-shaped nephron precursors.
• Glomerular capillaries invade the developing renal corpuscles.
• Nephrons establish continuity with collecting tubules.
• The kidneys initially develop in the pelvic region.
• They subsequently ascend to the posterior abdominal wall.
• The kidneys rotate during ascent so that their hila become medially directed.
• The renal arterial supply changes repeatedly during ascent.
• Persistence of temporary vessels can produce accessory renal arteries.

Clinical Importance

The metanephros is fundamental to understanding congenital renal anatomy because virtually every major structural component of the permanent kidney develops through interaction between the ureteric bud and metanephric mesenchyme. Disturbance of either component can alter kidney formation, collecting-system anatomy, or nephron development.

Changes occurring after initial kidney formation are equally important. Abnormal ascent can produce an ectopic kidney, fusion can produce a horseshoe kidney, abnormal rotation can alter hilar orientation, and persistence of transient vascular channels can produce accessory renal arteries. Abnormal ureteric bud development can also result in duplicated collecting systems and ureteric anomalies.

Understanding the metanephros provides the embryological foundation for studying permanent kidney development, nephrogenesis, ureteric bud branching, metanephric mesenchyme, renal ascent and rotation, renal agenesis, ectopic kidney, horseshoe kidney, duplicated ureters, and congenital abnormalities of the urinary system.