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Development of the Kidney with Developmental Anomalies

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OVERVIEW

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THREE SUCCESSIVE KIDNEY SYSTEMS

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1. PRONEPHROS

Key point: Although the pronephros is vestigial, the pronephric duct persists and is taken over by the mesonephros to become the mesonephric (Wolffian) duct.

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2. MESONEPHROS

• In males: a few caudal tubules + the mesonephric duct persist to form the epididymis, vas deferens, ejaculatory duct, seminal vesicles.
• In females: the mesonephric duct disappears (vestigial remnants may remain as Gartner duct cysts).

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3. METANEPHROS (The Permanent/Definitive Kidney)

Two Sources of the Metanephros

• Outgrowth of the mesonephric duct close to its entrance into the cloaca
• Penetrates the metanephric mesoderm (metanephric blastema/cap)
• The bud dilates to form the primitive renal pelvis, then splits into cranial and caudal parts - the future major calyces
• Each calyx forms 2 new buds, continuing to subdivide (~12+ generations of tubules) forming:
  • Major calyces
  • Minor calyces
  • Collecting tubules
  • Collecting ducts

1. Tissue cap cells form small vesicles → renal vesicles
2. Renal vesicles form small S-shaped tubules
3. Capillaries grow into one end → differentiate into glomeruli
4. Proximal end of tubule forms Bowman capsule (deeply indented by glomerulus)
5. Distal end opens into a collecting tubule (establishing a passageway from Bowman capsule to collecting unit)
6. Continuous lengthening forms:
   • Proximal convoluted tubule (PCT)
   • Loop of Henle
   • Distal convoluted tubule (DCT)

Key summary: The kidney develops from two sources:

1. Metanephric mesoderm → provides excretory units (nephrons)
2. Ureteric bud → gives rise to the collecting system

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MOLECULAR REGULATION OF KIDNEY DEVELOPMENT

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ASCENT (POSITIONAL CHANGE) OF THE KIDNEY

• Metanephros initially lies in the pelvic region
• Ascends to the lumbar/abdominal position due to:
  • Diminution of body curvature
  • Growth of the body in lumbar and sacral regions
• As it ascends, vascular supply shifts from pelvic branches to progressively higher aortic branches
• The kidney also rotates medially ~90° so the hilum faces medially

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DEVELOPMENTAL ANOMALIES OF THE KIDNEY

1. Renal Agenesis

• Caused by bilateral renal agenesis → oligohydramnios → uterine compression
• Features: flattened face (Potter facies), club feet, pulmonary hypoplasia (life-threatening), limb deformities
• Associated defects: cardiac anomalies, tracheal/duodenal atresias, cleft lip/palate, brain abnormalities
• Severe associated reproductive tract defects: absent/abnormal vagina and uterus (females), absent vas deferens/seminal vesicles (males)

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2. Ectopic (Pelvic) Kidney

• During ascent through the arterial fork formed by the umbilical arteries, one kidney may fail to pass through
• Remains in the pelvis close to the common iliac artery = pelvic kidney
• The kidney retains its fetal (pelvic) blood supply
• Usually asymptomatic, but prone to:
  • Hydronephrosis (angulation of ureter)
  • Urinary tract infections
  • Renal calculi

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3. Horseshoe Kidney

• Most common fusion anomaly of the kidney (1 in 400-500 people)
• Mechanism: During passage through the arterial fork of the umbilical arteries, both kidneys are pushed together and their lower poles fuse
• The fused mass (horseshoe) is usually at the level of the lower lumbar vertebrae (specifically L3), trapped beneath the inferior mesenteric artery - which prevents complete ascent
• The isthmus connecting the two kidneys is typically parenchymal or fibrous
• Clinical implications:
  • Increased risk of ureteropelvic junction obstruction
  • Increased risk of renal calculi and UTI
  • Associated with Turner syndrome (45, XO)

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4. Polycystic Kidney Disease (PKD)

• Bardet-Biedl syndrome: renal cysts + obesity + intellectual disability + limb defects
• Meckel-Gruber syndrome: renal cysts + hydrocephalus + microphthalmia + cleft palate + absence of olfactory tract + polydactyly

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5. Duplex (Double) Ureter and Collecting System

• Results from early splitting of the ureteric bud before it contacts the metanephric blastema
• May be:
  • Partial duplication - ureters join before entering the bladder
  • Complete duplication - two separate ureters entering the bladder (or elsewhere)
• Metanephric tissue may be divided into two parts, each with its own renal pelvis and ureter
• Ectopic ureter: results from development of two ureteric buds; the abnormal bud moves down together with the mesonephric duct and opens into the vagina, urethra, or vestibule (females) or epididymal region (males)
  • In females: the ectopic ureteral opening below the external urethral sphincter causes continuous dribbling of urine despite normal micturition

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6. Multicystic Dysplastic Kidney (MCDK)

• Results from failure of the ureteric bud to contact the metanephric mesoderm or from atresia of the ureter early in development
• Kidney is non-functional and replaced by cysts
• Usually unilateral (bilateral = incompatible with life)

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Summary Table: Developmental Anomalies at a Glance

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QUICK EXAM REVISION MNEMONICS

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FREQUENTLY ASKED EXAM POINTS

1. Pronephros = vestigial, non-functional, disappears by end of week 4
2. Mesonephros = functional temporarily; mesonephric duct is key (becomes Wolffian duct; forms male genital ducts)
3. Metanephros = permanent kidney; appears week 5, functional week 12
4. The kidney develops from TWO sources (must state both for full marks)
5. Kidney ascent: pelvic → abdominal; rotation: hilum faces medially
6. ~1 million nephrons at birth; no new nephrons form after birth
7. WT1 mutation → associated with Wilms tumor (nephroblastoma) in children - one of the most common childhood abdominal tumors
8. Horseshoe kidney: most common fusion anomaly, halted by inferior mesenteric artery
9. Potter sequence: always explain the mechanism (bilateral agenesis → oligohydramnios → compression → features)
10. Polycystic kidney = ciliopathy (high-yield molecular fact)

• Langman's Medical Embryology, 14th Edition - Chapter 16: Urogenital System