Development of the Kidney

Origin

Three Successive Kidneys

1. Pronephros (Week 3-4)

• Appears at the end of the 3rd week in the cervical region
• Represented by 7-10 solid cell groups (nephrotomes) - vestigial and non-functional in humans
• Completely degenerates by the end of the 4th week
• Its duct - the pronephric duct - persists and is taken over as the mesonephric (Wolffian) duct

2. Mesonephros (Week 4 - Month 2)

• Derived from intermediate mesoderm of the upper thoracic to upper lumbar (L3) segments
• First excretory tubules appear early in the 4th week as the pronephros regresses
• Tubules form S-shaped loops, acquire glomeruli, and develop Bowman's capsule - forming renal corpuscles
• Laterally, each tubule drains into the mesonephric (Wolffian) duct, which extends caudally to join the cloaca
• By the middle of the 2nd month, the mesonephros forms a large paired ovoid organ
• Cranial tubules degenerate first; by the 4th month most have disappeared
• Remnants in males: efferent ductules of testis, epididymis, vas deferens
• Remnants in females: epoophoron and paroophoron (within the broad ligament)

3. Metanephros (Week 5 onwards) - The Permanent Kidney

• Begins developing around week 5 in the sacral region
• Has two components that interact by reciprocal induction:

a) Ureteric Bud (Metanephric Diverticulum)

• An outgrowth from the mesonephric duct near its entrance into the cloaca
• Elongates cranially and penetrates the metanephric mesenchyme (blastema)
• Undergoes dichotomous branching - first into cranial and caudal divisions (future major calyces)
• Each calyx buds further; 12 or more generations of tubules form by end of 5th month
• 2nd-order branches absorbed → minor calyces; 5th and subsequent generations elongate → renal pyramids
• Gives rise to: ureter, renal pelvis, major and minor calyces, collecting ducts (~1-3 million)

b) Metanephric Mesenchyme (Blastema)

• Caps the ureteric bud distally
• Induced by the ureteric bud to undergo mesenchymal-to-epithelial transition (MET)
• Forms vesicles → S-shaped bodies → nephrons
• Each nephron: glomerulus + Bowman's capsule + proximal tubule + loop of Henle + distal tubule
• Distal tubule opens into the collecting duct system derived from the ureteric bud

Key Diagram

Relationship of intermediate mesoderm of pronephric, mesonephric, and metanephric systems. Note the ureteric bud sprouting from the mesonephric duct (Langman's Medical Embryology)

Ureteric bud penetrating the metanephric blastema at the end of the 5th week (Langman's Medical Embryology)

Ascent of the Kidney

• The metanephros initially lies in the sacral region
• As the embryo grows, the kidneys appear to ascend to their final lumbar position (actually due to differential growth of the lumbar and sacral regions)
• Blood supply is acquired at progressively higher levels from the aorta
• The hilum, initially facing anteriorly, rotates medially ~90° during ascent
• Failure of rotation = malrotated kidney; failure of ascent = pelvic kidney

Nephron Endowment

• Full complement of nephrons reached by 36 weeks of gestation (no new nephrons form postnatally)
• Humans average ~1 million nephrons per kidney (range variable)
• Reduced nephron number at birth raises risk for hypertension and chronic kidney disease in adult life

Summary Table