340.3 🏥 內科專科考前版

340.3.1 Mechanistic Deep Dive

340.3.1.1 Podocyte Biology

  • Foot processes + slit diaphragm (nephrin, podocin)
  • Maintain filtration barrier
  • Injury → foot process effacement → proteinuria
  • MCD, FSGS, MN all involve podocyte damage (different mechanisms)

340.3.1.2 Anti-PLA2R Discovery (2009)

  • Phospholipase A2 receptor
  • Target antigen on podocytes
  • 70-80% of primary MN
  • THSD7A + NELL-1 minor antibodies

340.3.1.3 Complement in GN

  • C3G: alternative pathway dysregulation
  • Eculizumab: terminal complement (C5)
  • Iptacopan: factor B (alternative pathway)

340.3.1.4 ANCA Pathophysiology

  • ANCA binds neutrophil antigens
  • TNF-primed neutrophils
  • Neutrophil degranulation → endothelial damage
  • Crescent formation

340.3.2 Recent Trials & Updates

340.3.2.1 MENTOR (2019) — Rituximab MN

  • Rituximab vs cyclosporine
  • Better remission + safer
  • First-line for primary MN

340.3.2.2 TESTING (2017, 2022) — Methylprednisolone IgA

  • Oral methylprednisolone in high-risk IgA
  • Reduced eGFR decline
  • Safety concerns

340.3.2.3 DUPLEX (2023) — Sparsentan FSGS

  • ↓ Proteinuria vs irbesartan
  • FDA approved 2023 (FSGS)

340.3.2.4 PROTECT (2023) — Sparsentan IgA

  • ↓ Proteinuria vs irbesartan
  • FDA approved for IgA 2023

340.3.2.5 NefigaRD (2021) — Nefecon IgA

  • Targeted-release budesonide
  • ↓ Proteinuria + eGFR preservation
  • FDA approved 2021

340.3.2.6 APPLAUSE-IgAN (Ongoing) — Iptacopan

  • Factor B inhibitor
  • Promising results

340.3.2.7 BLISS-LN (2020) — Belimumab Lupus

  • BAFF inhibitor
  • Added to standard
  • ↑ Renal response

340.3.2.8 AURORA (2020) — Voclosporin Lupus

  • New CNI
  • More potent
  • ↓ Proteinuria added to MMF

340.3.2.9 PEXIVAS (2020) — Plasmapheresis + Steroid Dose ANCA

  • Plasmapheresis benefit limited (subgroups)
  • Reduced steroid dose acceptable

340.3.2.10 ADVOCATE (2021) — Avacopan ANCA

  • C5a receptor antagonist
  • Steroid-sparing
  • FDA approval 2021

340.3.2.11 Inaxaplin (AMPLITUDE Ongoing) — APOL1

  • Targeted for APOL1 nephropathy
  • Phase 3 trial

340.3.2.12 ANDROMEDA (2021) — Dara-VCD AL Amyloid

  • Daratumumab + bortezomib + cyclophosphamide + dexamethasone
  • Front-line for AL amyloid

340.3.3 High-Yield Specialist Points

340.3.3.1 MCD Adult Specifics

  • Higher relapse + steroid resistance
  • More cytotoxic IS needed
  • Adult variants: think lithium, NSAIDs, Hodgkin
  • Rituximab effective for relapsers

340.3.3.2 FSGS Recurrence Post-Transplant

  • Primary FSGS: 20-30% recurrence
  • Within hours-days
  • Plasmapheresis pre/post-transplant
  • ICZ apheresis, rituximab for severe

340.3.3.3 MN Anti-PLA2R Monitoring

  • Levels correlate with disease activity
  • Decline predicts treatment response
  • Persistent positivity suggests need for further IS

340.3.3.4 IgA Nephropathy MEST-C Scoring

  • Oxford classification
  • Prognostic value
  • Guides treatment intensity

340.3.3.5 Lupus Nephritis Class V Pure

  • Mostly nephrotic
  • Treatment: supportive (RAAS) ± IS if severe

340.3.3.6 ANCA-Associated Renal-Limited Vasculitis

  • Some cases isolated renal
  • Same IS approach

340.3.3.7 Hereditary GN Considerations

  • Alport syndrome: type IV collagen
  • Thin GBM disease: COL4A3/4 heterozygous
  • Genetic testing
  • Family screening
  • Hearing loss + eye findings in Alport

340.3.3.8 Drug-Induced GN

  • NSAIDs: MCD, AIN
  • ICI: ATN, AIN, MCD, MN, lupus nephritis-like
  • Penicillamine: MN, ANCA
  • Hydralazine: lupus-like, ANCA
  • Pamidronate: collapsing FSGS

340.3.3.9 Cancer-Associated GN

  • MN: solid tumors (colon, lung, breast, prostate)
  • MCD: Hodgkin
  • AL amyloid: myeloma
  • Cryoglobulinemia: lymphoma, hep C
  • Membranoproliferative: monoclonal gammopathy

340.3.3.10 Pregnancy + GN

  • Lupus nephritis particularly important
  • IS adjustment (avoid MMF, cyclophosphamide; use AZA)
  • Plasma exchange OK for severe
  • Multidisciplinary

340.3.3.11 Renal Biopsy in Specific Conditions

  • Hep C + NS: MPGN, MN
  • HIV + NS: FSGS (collapsing), HIVAN
  • Older adult NS: rule out MN; consider amyloid + monoclonal
  • AKI on top of CKD: consider drug-induced AIN, RPGN

340.3.3.12 Avacopan Use

  • ANCA-associated vasculitis
  • Steroid-sparing
  • Long-term safety being assessed
  • Approved adjunct

340.3.3.13 Sparsentan Practical Use

  • Dual ETA + AT1R antagonist
  • Replace ACE/ARB
  • ↓ Proteinuria
  • Monitor: BP, K, Cr
  • BP may be lower than expected

340.3.3.14 Iptacopan Mechanism

  • Factor B inhibitor (alternative complement)
  • Oral
  • For C3G + IgA emerging
  • Phase 3 trials

340.3.4 Pearls

  • MCD: kids, steroids; foot process effacement
  • FSGS: adults US; APOL1; collapsing variant worst
  • MN: anti-PLA2R 70-80%; rituximab MENTOR; renal vein thrombosis
  • IgA: globally most; synpharyngitic; Nefecon FDA 2021
  • Lupus: ISN/RPS I-VI; MMF + steroids + voclosporin/belimumab
  • ANCA: pauci-immune; rituximab + steroids + avacopan FDA 2021
  • Anti-GBM: plasmapheresis + cyclophosphamide + steroids
  • MPGN/C3G: iptacopan emerging
  • DKD: 4 pillars
  • AL amyloid: daratumumab + CyBorD