342.4 ð ç« æ«éèš Summary
342.4.1 ð äžå¥è©±çžœçµ
ADPKD (autosomal dominant polycystic kidney disease) = æåžžèŠ hereditary kidney disease (1/400-1000)ïŒPKD1 (chromosome 16, 85%, more severe, ESKD ~ 60 yo) > PKD2 (chromosome 4, 15%, slower, ESKD ~ 75 yo) mutationsïŒclinical featuresïŒbilateral renal cysts + HTN (70-80% often early) + hematuria + flank pain + recurrent UTI + stones + progressive CKD â ESKDïŒextrarenalïŒliver cysts (70-90%) + intracranial Berry aneurysm (5-15% â screen if family history of aneurysm) + mitral valve prolapse (25%) + colonic diverticulosis + abdominal hernias + aortic aneurysmïŒdiagnosisïŒUS (modified Ravine criteria + family history); CT/MRI; Mayo Clinic Classification 1A-1E based on htTKV for risk stratificationïŒtreatmentïŒstandard CKD management + tolvaptan (vasopressin V2 receptor antagonist) for rapid progressors (TEMPO 3:4 2012, REPRISE 2017) â LFT monitoring + REMS programïŒARPKD (PKHD1) = pediatric severe + hepatic fibrosis (Caroli) + pulmonary hypoplasia neonatalïŒAlport syndrome = type IV collagen defects (COL4A5 X-linked > COL4A3/4 AR)ïŒhematuria + sensorineural hearing loss + ocular (anterior lenticonus pathognomonic) â ACE/ARB + SGLT2i emergingïŒthin basement membrane nephropathy (TBMN) = COL4A3/4 heterozygous = benign familial hematuriaïŒFabry disease = X-linked α-Gal-A deficiency (GLA mutation) = multi-organ (renal FSGS-like + cardiac HCM + neurologic acroparesthesias + skin angiokeratomas + ocular cornea verticillata) â ERT (agalsidase α/β) + migalastat (chaperone for amenable mutations) + pegunigalsidase (PRX-102, FDA 2023, long-acting)ïŒnephronophthisis (NPHP) = ciliopathy juvenile CKD + polyuria + anemia + growth failureïŒTSC + VHL distinct multi-organ syndromes (angiomyolipomas/mTOR inhibitor vs cysts + RCC + hemangioblastoma + pheochromocytoma)ã
342.4.2 ð æ²»ç粟èŠ
- ADPKD standardïŒBP control (ACE/ARB) + standard CKD management (Ch335) + avoid nephrotoxins + cyst infection management
- ADPKD-specificïŒtolvaptan (TEMPO 3:4, REPRISE) for rapid progressors (Mayo class 1C-1E, eGFR 25-90); LFT monitoring + REMS; daily fluid 3-4 L
- ADPKD intracranial aneurysmïŒscreen with MRA/CTA q 5-10 yr if family hx of aneurysm; > 7 mm typically treat (coiling or clipping)
- ARPKDïŒsupportive + transplant for ESKD + hepatic management (Caroli, varices)
- Alport syndromeïŒACE/ARB (slow progression); SGLT2i emerging; hearing aids + ocular surveillance; transplant for ESKD (watch for anti-GBM in some)
- TBMNïŒobservation + ACE/ARB if proteinuria
- FabryïŒERT agalsidase α (Replagal) or β (Fabrazyme) IV q 2 weeks; migalastat (Galafold) oral for amenable mutations (~ 50% patients); pegunigalsidase (PRX-102, FDA 2023) monthly long-acting; supportive (ACE/ARB, cardiac, neuropathy)
- NPHPïŒsupportive + transplant for ESKD
- TSC + angiomyolipomas > 4 cmïŒeverolimus or sirolimus (mTOR inhibitors)
- VHLïŒsurveillance imaging + early surgery for RCC + hemangioblastoma
342.4.3 ð¯ ç§é«åž«çèåæé
- ADPKD genetic dichotomyïŒPKD1 (85%, chromosome 16, polycystin-1, ESKD ~ 60 yo) vs PKD2 (15%, chromosome 4, polycystin-2, ESKD ~ 75 yo) â PKD2 progresses more slowly
- ADPKD extrarenal manifestations criticalïŒliver cysts (most common 70-90%, F > M, estrogen) + intracranial Berry aneurysm (5-15%) + MV prolapse 25% + diverticulosis + abdominal hernias + aortic aneurysm
- Mayo Clinic Classification 1A-1E for ADPKDïŒbased on htTKV (height-adjusted total kidney volume); guides tolvaptan eligibility (1C-1E)
- tolvaptan TEMPO 3:4 (2012) + REPRISE (2017)ïŒslows cyst growth + GFR decline in ADPKD; hepatotoxicity major concern (REMS + LFT monitoring) + polyuria + polydipsia (daily fluid 3-4 L)
- intracranial aneurysm screening in ADPKDïŒfamily history of aneurysm OR high-risk occupation (pilot, military) â MRA/CTA q 5-10 yrïŒ> 7 mm typically treat
- Alport syndrome classical triadïŒhematuria + sensorineural hearing loss (high-frequency) + ocular anterior lenticonus (pathognomonic)ïŒEM shows basket-weave appearance of GBM
- Alport post-transplant complicationïŒdevelopment of anti-GBM disease against donor kidney (rare); plasmapheresis + IS
- Fabry disease multi-organ classic featuresïŒrenal (proteinuria + FSGS-like, foam cells) + cardiac (concentric HCM mimicking HCM) + neurologic (acroparesthesias, stroke, hypohidrosis) + skin (angiokeratomas in âbathing trunkâ distribution) + ocular (cornea verticillata)
- Fabry treatmentïŒERT (agalsidase α or β IV q 2 wk) + migalastat (Galafold oral for ~ 50% with amenable mutations) + pegunigalsidase (PRX-102 FDA 2023 monthly long-acting)
- thin basement membrane nephropathy (TBMN) vs AlportïŒTBMN = heterozygous COL4A3/4 = autosomal dominant; benign familial hematuria; carrier for AR Alport; observation