Developmental abnormalities and cystic diseases of the kidney

1. Developmental Abnormalities

A) Complete (bilateral) renal agenesis

• Both kidneys absent.
• Very uncommon; incompatible with life.
• Causes oligohydramnios (fetal urine is the main amniotic fluid source).
• Contributes to Potter sequence:
  • Flattened nose, low-set ears, recessed chin
  • Pulmonary hypoplasia → fatal (amniotic fluid needed for lung maturation)
  • Limb deformities (club feet)

B) Unilateral renal agenesis

• One kidney absent.
• More common; usually adequate renal function via compensatory hypertrophy of the remaining kidney.
• Higher risk of glomerulosclerosis, proteinuria, HTN with age.

C) Renal ectopia

• Abnormal kidney localization, frequently pelvic kidney.
• Function usually normal.

D) Horseshoe kidney (renal fusion)

• Congenital fusion of both kidneys, usually at lower poles.
• Caught beneath inferior mesenteric artery during ascent.
• ↑ Risk of:
  • Urinary obstruction (abnormal ureter course)
  • Infection (vesicoureteral reflux)
  • Kidney stones

2. Cystic Diseases of the Kidney

Heterogenous group — hereditary, developmental non-hereditary, acquired. Clinical importance: common; diagnostic challenge; some cause chronic renal failure; may mimic tumors.

A) Simple cysts

• Most common cystic lesion.
• No clinical significance — only matters for distinguishing from tumors.
• Single or multiple, 1–5 cm, smooth-walled, translucent fluid.
• Single layer of cuboidal epithelium.

B) Dialysis-associated acquired cystic disease

• Occurs in end-stage kidney patients on prolonged dialysis.
• Cause: chronic ischemia → interstitial fibrosis → tubular compression → dilation.
• Cysts in cortex + medulla.
• Risk of renal cell carcinoma from cyst lining.

C) Autosomal Dominant PKD (ADPKD, “adult type”)

• Inherited disorder — bilateral multiple fluid-filled cysts progressively destroy parenchyma.

Genetics

• PKD1 (85–90 %, chr 16) → polycystin 1 (cell-cell / cell-ECM adhesion).
• PKD2 (10–15 %, chr 4) → polycystin 2 (Ca²⁺ channel).
• Polycystin 1 + 2 form a complex; PKD2 mutation = slower progression.

Morphology

• Initially preserved nephrons between cysts.
• Cysts enlarge → compress → ischemic atrophy.
• Full-blown: kidneys 4–5 kg each, bilateral; cyst fluid clear / turbid / hemorrhagic.

Clinical course

• Usually asymptomatic until 4th decade → pain, hematuria, HTN, UTI.
• Slow progression; renal failure by 5th decade.
• Associations:
  • Berry aneurysms (circle of Willis) → subarachnoid hemorrhage
  • Liver cysts, mitral valve prolapse
• Tx end-stage: kidney transplantation.

D) Autosomal Recessive PKD (ARPKD, “childhood type”)

• AR inheritance; much more uncommon but more severe.
• Forms: neonatal, infantile, juvenile.

Genetics

• PKHD1 → fibrocystin (membrane receptor).
• Mutation → dysgenesis of collecting tubules → cyst formation.

Morphology

• Numerous small cysts in cortex + medulla from collecting tubules → sponge-like kidney.
• Liver cysts; congenital hepatic fibrosis.

Clinical course

• Often die from renal / liver failure in infancy.
• Survivors develop liver cirrhosis (congenital hepatic fibrosis).

E) Medullary cystic disease (nephronophthisis-medullary cystic complex)

• Rare; cysts at corticomedullary junction.
• AD or AR (≥ 7 genes).
• Kidneys small, contracted.
• Initial Sx: polyuria, polydipsia (tubular dysfunction).
• Progresses to chronic renal failure in 5–10 yr.

3. ADPKD vs ARPKD

Feature	ADPKD (adult)	ARPKD (childhood)
Inheritance	Autosomal dominant	Autosomal recessive
Gene / protein	PKD1/PKD2 → polycystin 1/2	PKHD1 → fibrocystin
Onset	4th–5th decade	Neonatal / infantile
Kidney	Huge bilateral, large cysts	Sponge-like, small cysts (collecting tubules)
Associations	Berry aneurysm, liver cysts, MVP	Congenital hepatic fibrosis → cirrhosis
Prognosis	Renal failure 5th decade → transplant	Often fatal in infancy

💡 High-yield: Bilateral renal agenesis → oligohydramnios → Potter sequence (pulmonary hypoplasia, flat nose, low-set ears). Horseshoe kidney = fusion at lower poles, caught under IMA; stones, infection, obstruction. ADPKD: PKD1/PKD2, adult onset, Berry aneurysm, HTN, hematuria. ARPKD: PKHD1/fibrocystin, infant onset, congenital hepatic fibrosis. Simple cysts = most common, no significance.