It is classified into two distinct disorders: autosomal recessive PKD (ARPKD) and autosomal dominant PKD (ADPKD).
Epidemiology
ADPKD: The most common inherited cause of chronic kidney disease
Etiology
- ADPKD
- PKD1 on chromosome 16 (85% of cases)
- PKD2 on chromosome 4 (15% of cases)
- ARPKD
- Mutation in PKHD1 gene on chromosome 6
Mnemonic
Polycystic Kidney = 16 letters! = Chromosome 16
Pathophysiology
Formation and expansion of cysts in the renal cortex and medulla → compression of renal vessels with activation of the renin-angiotensin-aldosterone system (RAAS), ischemia, and destruction of the kidney parenchyma
Clinical features
- ADPKD (Adult-onset):
- Renal Manifestations:
- Bilateral flank/abdominal pain (due to cyst growth, hemorrhage, or infection).
- Gross or microscopic hematuria (due to cyst rupture).
- Bilateral, palpable flank masses. c
- Nephrolithiasis (typically uric acid or calcium oxalate).
- Extrarenal Manifestations:
- Cerebral berry aneurysms (in Circle of Willis; rupture causes subarachnoid hemorrhage).
- Hepatic cysts (most common extrarenal finding). c
- Pancreatic, splenic, and ovarian cysts.
- Mitral valve prolapse (MVP) (mid-systolic click, late systolic murmur) or aortic regurgitation.
- Colonic diverticulosis.
- Abdominal wall or inguinal hernias.
- Renal Manifestations:
- ARPKD (Infantile-onset):
- Prenatal: Oligohydramnios leading to Potter sequence (pulmonary hypoplasia, flat facies, clubfeet).
- Neonatal/Infant: Massive bilateral flank masses, severe respiratory distress (from pulm hypoplasia), severe HTN.
Diagnostics
| Feature | ADPKD (Adult) | ARPKD (Infantile) |
|---|---|---|
| Gene | PKD1/PKD2 | PKHD1 |
| Onset | Adulthood (30-40s) | In Utero / Infancy |
| Presentation | HTN, flank pain, hematuria | Potter sequence, neonatal respiratory distress |
| Liver Disease | Hepatic cysts | Congenital hepatic fibrosis, portal HTN |
| Key Association | Berry aneurysms | Pulmonary hypoplasia |
| Prognosis | ESRD ~age 60 | High neonatal mortality; ESRD in childhood |
- ADPKD:
- Initial/Confirmatory: Renal Ultrasound (US). Diagnostic criteria based on age + number of cysts (e.g., ≥3 cysts per kidney if age 15-39).
- Key Labs: UA (hematuria, proteinuria), CMP (progressive ↑ BUN/Cr).
- Advanced Imaging: CT/MRI abd/pelvis used if US is equivocal or to assess cyst complications (hemorrhage vs infection).
- Note: Routine screening for berry aneurysms (MRA/CTA brain) is ONLY indicated if high-risk (e.g., family hx of SAH, previous rupture, high-risk occupation).
- ARPKD:
- Prenatal: Fetal US (bilateral enlarged, echogenic kidneys + oligohydramnios).
- Postnatal Initial: Renal US (diffuse microcysts, loss of corticomedullary differentiation) + Hepatic US (fibrosis).
- Genetic Testing: Gold standard if US findings are ambiguous.