342.2 𩺠åèç
342.2.1 é«é »èé»
342.2.1.1 ADPKD
- 1/400-1000 prevalence
- PKD1 (85%, chromosome 16) > PKD2 (15%, chromosome 4)
- PKD1 more severe; PKD2 slower
- Bilateral renal cysts + extrarenal
- HTN often early
- ESKD ~ 50% by 60 yo (PKD1); ~ 75 (PKD2)
342.2.1.2 Extrarenal Manifestations ADPKD
- Liver cysts (70-90%)
- Intracranial (Berry) aneurysm (5-15%)
- MV prolapse (25%)
- Diverticulosis
- Abdominal hernias
- Aortic aneurysm
342.2.1.3 Mayo Clinic Classification (1A-1E)
- Based on htTKV
- 1A slowest; 1E fastest
- Guides tolvaptan use
342.2.1.4 Tolvaptan
- V2 receptor antagonist
- TEMPO 3:4 (2012), REPRISE (2017)
- For rapid progressors
- LFT monitoring (hepatotoxicity)
- REMS program
342.2.1.5 Intracranial Aneurysm Screening
- Family history of aneurysm
- High-risk occupation
- MRA or CTA q 5-10 years
342.2.1.6 ARPKD
- PKHD1 (autosomal recessive)
- Pediatric, severe
- Hepatic fibrosis (Caroli)
- Pulmonary hypoplasia (severe neonatal)
342.2.1.7 Alport Syndrome
- COL4A5 (X-linked, most), COL4A3/4 (AR)
- Hematuria + sensorineural hearing loss + ocular (anterior lenticonus)
- ACE/ARB; SGLT2i emerging
- Post-transplant: anti-GBM disease risk
342.2.1.9 Fabry Disease
- X-linked, α-Gal-A deficiency
- Globotriaosylceramide accumulation
- Renal (FSGS-like) + cardiac (HCM) + neurologic (acroparesthesias, stroke) + skin (angiokeratomas) + ocular (cornea verticillata)
- ERT: agalsidase α/β
- Migalastat for amenable mutations
- Pegunigalsidase (FDA 2023, long-acting)
342.2.2 ææ··æ·æ¯èŒ
| Disease | Genetics | Key Features | Treatment |
|---|---|---|---|
| ADPKD | AD, PKD1/2 | Bilateral cysts + extrarenal | Tolvaptan + standard CKD |
| ARPKD | AR, PKHD1 | Pediatric, hepatic fibrosis | Supportive |
| Alport | XL (COL4A5) | Hematuria + hearing + ocular | ACE/ARB |
| Thin GBM | AD (COL4A3/4 heterozygous) | Benign familial hematuria | Monitor |
| Fabry | XL, GLA | Multi-organ + angiokeratomas | ERT, migalastat, pegunigalsidase |
| NPHP | Ciliopathy | Juvenile CKD + polyuria | Supportive |
| TSC | TSC1/2 | Angiomyolipomas + LAM | mTOR inhibitor |
| VHL | VHL gene | Cysts + RCC + hemangioblastoma | Surveillance + surgery |
342.2.3 Special Topics
342.2.3.1 ADPKD Diagnostic Criteria
- Family history + age-appropriate cysts:
- 15-39 yo: ⥠3 cysts (any location)
- 40+ yo: ⥠2 cysts each kidney
- Or genetic testing
342.2.3.2 Tolvaptan Side Effects
- Hepatotoxicity (LFT q 1 mo first 18 mo, then q 3 mo)
- Polyuria, polydipsia, thirst
- Hyperphosphatemia (some)
- Hyperuricemia
- REMS program enrollment