340.1 🎓 醫孞生版

340.1.0.1 📌 䞀頁重點

340.1.1 Minimal Change Disease (MCD)

Epidemiology: - Most common cause of NS in children (80%) - Less common in adults (~ 10-20%) - Idiopathic mostly

Pathology: - Light microscopy: normal (or near-normal) - Immunofluorescence: negative - Electron microscopy: podocyte foot process effacement

Clinical: - Sudden onset edema, anasarca - Heavy proteinuria - Hypoalbuminemia - Hyperlipidemia - Selective proteinuria (mostly albumin) - Excellent response to steroids

Treatment: - Corticosteroids (prednisone 1 mg/kg/d in adults, 60 mg/m² in children) - 80-90% remit within 4-8 weeks - Frequent relapsers: cyclophosphamide, MMF, rituximab, calcineurin inhibitors

Adult MCD Differential: - Hodgkin lymphoma - Lithium - NSAIDs - Idiopathic

340.1.2 Focal Segmental Glomerulosclerosis (FSGS)

Epidemiology: - Most common cause of NS in adults in US - African ancestry overrepresented (APOL1 G1/G2) - All ages

Pathology: - Light microscopy: focal (some glomeruli) + segmental (part of glomerulus) sclerosis - Immunofluorescence: variable (segmental IgM, C3) - Electron microscopy: podocyte foot process effacement

Variants (Columbia Classification): - NOS (not otherwise specified) — most common - Perihilar — secondary - Tip — better prognosis - Cellular — intermediate - Collapsing — worst prognosis (HIV, viral, APOL1)

Etiology: - Primary (idiopathic): circulating permeability factor; suPAR investigated - Genetic: NPHS1, NPHS2 (podocin), TRPC6, ACTN4, INF2, APOL1 - Secondary: - HIVAN (collapsing): high viral load - Reflux nephropathy - Obesity - Heroin abuse - CMV, parvovirus B19 - Pamidronate - Anabolic steroid abuse - Post-AKI - Solitary kidney / reduced nephron mass - Sickle cell disease

Clinical: - NS (heavy proteinuria, edema) - Often HTN - Variable AKI - Hematuria (less than nephritic)

Treatment: - Primary: - Glucocorticoids (prednisone 1 mg/kg × 4 mo) - Steroid-dependent / resistant: cyclophosphamide, MMF, rituximab, CNIs (tacrolimus, cyclosporine) - Sparsentan (DUPLEX trial 2023) — emerging - Genetic: less responsive to IS; supportive - Secondary: treat underlying (HIV ART, weight loss, control reflux) - Recurrent post-transplant: aggressive (plasmapheresis, rituximab, ICZ apheresis)

340.1.3 Membranous Nephropathy (MN)

Epidemiology: - Most common cause of NS in older adults (60+) - Male > female

Pathology: - Light microscopy: diffuse thickening of GBM (silver stain “spikes”) - Immunofluorescence: granular IgG + C3 along GBM - Electron microscopy: subepithelial dense deposits

Antibodies: - Anti-PLA2R (phospholipase A2 receptor): 70-80% of primary MN - Anti-THSD7A (thrombospondin type-1 domain containing 7A): 3-5% - Anti-NELL-1: may be associated with cancer - Other newer antibodies discovered

Etiology: - Primary (idiopathic): anti-PLA2R or anti-THSD7A - Secondary: - Hepatitis B (chronic) - SLE (Class V lupus nephritis) - Malignancy (10-20% of older MN — colon, lung, breast, prostate) - Drugs: penicillamine, gold, NSAIDs, captopril - Autoimmune: RA, sjögren

Clinical: - Slow-onset NS - Massive proteinuria - Significant hypoalbuminemia - Renal vein thrombosis risk (especially when albumin < 2.5) - Pulmonary embolism, DVT

Treatment: - Spontaneous remission in 30% - Anti-PLA2R titer: monitor (decline correlates with response) - Primary MN with active disease: - Rituximab (MENTOR 2019) — first-line for most - Cyclophosphamide + steroids (Ponticelli regimen) — older option - Calcineurin inhibitors (tacrolimus or cyclosporine) — alternative - Secondary MN: treat underlying - Prophylactic anticoagulation: if albumin < 2.0-2.5

340.1.4 IgA Nephropathy (Berger Disease)

Epidemiology: - Most common GN globally - Variable presentation - Especially Asia (Japan), Europe - Family clustering

Pathology: - Light microscopy: mesangial hypercellularity - Immunofluorescence: mesangial IgA deposits (predominantly IgA1) - Electron microscopy: mesangial deposits

Clinical: - Synpharyngitic gross hematuria (within 1-2 days of URI — classic) - Microscopic hematuria + variable proteinuria (asymptomatic) - Slow progression - HTN - AKI in some

Risk Score: MEST-C (Oxford Classification) - M: mesangial hypercellularity - E: endocapillary hypercellularity - S: segmental sclerosis - T: tubular atrophy / interstitial fibrosis - C: crescents

Treatment: - ACE/ARB + BP control + ↓ proteinuria - SGLT2i (DAPA-CKD subgroup) - High-risk (proteinuria > 1 g/d on RAAS + ↓ eGFR): - Targeted-release budesonide (Nefecon) — FDA 2021 approved - Systemic steroids (TESTING trial) - Tonsillectomy + steroid pulses (Japanese standard) - Sparsentan (PROTECT 2023) — emerging - Iptacopan (APPLAUSE-IgAN) — complement inhibitor

340.1.5 Lupus Nephritis

Epidemiology: - 50-60% of SLE patients develop nephritis - F > M (esp younger)

ISN/RPS Classification 2003 (Class I-VI): - I: minimal mesangial — no treatment usually - II: mesangial proliferative — supportive - III: focal proliferative (< 50% glomeruli) — IS - IV: diffuse proliferative (≥ 50% glomeruli) — IS aggressive - V: membranous — IS or supportive - VI: advanced sclerotic — supportive, no IS - III/V or IV/V combinations common

Treatment (Class III/IV ± V):

Induction (3-6 months): - Cyclophosphamide IV (Eurolupus low-dose or NIH high-dose) — historically - MMF (mycophenolate mofetil) — increasingly preferred - Voclosporin (AURORA 2020) — CNI; ↓ proteinuria added to MMF - Belimumab (BLISS-LN 2020) — BAFF inhibitor; added to standard - Rituximab — alternative for refractory

Maintenance (years): - MMF (preferred) - Azathioprine - Low-dose prednisone - Hydroxychloroquine (all lupus)

Class V (Pure): - ACE/ARB + statin - IS if persistent NS

340.1.6 ANCA-Associated Vasculitis (AAV) — GPA, MPA, EGPA

Diseases: - GPA (granulomatosis with polyangiitis): PR3-ANCA (c-ANCA) - MPA (microscopic polyangiitis): MPO-ANCA (p-ANCA) - EGPA (eosinophilic granulomatosis with polyangiitis): MPO-ANCA (rare PR3)

Renal Involvement: - Pauci-immune crescentic GN (Type III RPGN) - Variable proteinuria - Hematuria + RBC casts - AKI

Systemic Features: - GPA: ENT (sinusitis, otitis), lung (granulomas), skin - MPA: lung (capillaritis), kidney predominant - EGPA: asthma + eosinophilia + neuropathy + cardiac

Treatment:

Induction: - Rituximab + steroids (PEXIVAS, RAVE, RITUXVAS) — preferred - Cyclophosphamide + steroids — alternative - Plasmapheresis for severe (alveolar hemorrhage, RPGN; PEXIVAS controversial — some benefit in subgroups) - Avacopan (C5a receptor antagonist) — adjunct, FDA 2021

Maintenance: - Rituximab (every 6 months) - Azathioprine or MMF

340.1.7 Anti-GBM Disease (Goodpasture)

Pathology: - Linear IgG along GBM - Crescents

Clinical: - Pulmonary-renal syndrome - Hemoptysis + RPGN - More common in young men + smokers

Antibodies: - Anti-GBM (against type IV collagen α3 chain) - Some ANCA dual-positive

Treatment: - Plasmapheresis (daily 14-21 days) — remove antibodies - Cyclophosphamide + steroids — IS - Rituximab — alternative - Emergent treatment

340.1.8 MPGN / C3 Glomerulopathy (C3G)

Pathology: - MPGN: mesangial + endothelial cells proliferation, “tram-track” on silver stain - C3G: predominant C3 on IF (DDD or C3GN)

Classification (Updated): - Immune complex-mediated: lupus, hep C, monoclonal Ig - Complement-mediated (C3G): DDD, C3GN; primary or secondary - Other: monoclonal gammopathy of renal significance (MGRS)

Treatment: - Treat underlying (lupus, hep C antiviral, monoclonal IS) - IS for primary: rituximab, MMF - Complement inhibitors emerging: iptacopan (factor B), eculizumab (terminal complement) for select

340.1.9 Diabetic Kidney Disease (DKD)

Epidemiology: - Globally most common cause of CKD + ESKD

Pathology: - Glomerular: GBM thickening, mesangial expansion, nodular sclerosis (Kimmelstiel-Wilson nodules), arteriolar hyalinosis - Tubular: thickened basement membranes - Interstitial: fibrosis

Clinical: - Microalbuminuria → macroalbuminuria → nephrotic-range proteinuria - Slow progression over years - HTN - Other DM complications (retinopathy, neuropathy)

Treatment (4 Pillars): - ACE/ARB (proteinuria) - SGLT2i (CREDENCE, DAPA-CKD) - Finerenone (FIDELIO/FIGARO) - GLP-1 RA (FLOW 2024) - BP < 130/80 - HbA1c < 7%

340.1.10 Amyloidosis

Types: - AL (light chain — myeloma-associated): plasma cell dyscrasia - AA (chronic inflammation — RA, IBD, FMF) - Hereditary (transthyretin, fibrinogen, lysozyme, others)

Pathology: - Congo red staining → apple-green birefringence - Mass spectrometry to type

Treatment: - AL: daratumumab + bortezomib + cyclophosphamide + dexamethasone (Dara-VCD, ANDROMEDA) - AA: treat underlying inflammation - ATTR-hereditary: tafamidis (cardiac), patisiran, vutrisiran (gene silencers)

340.1.11 Light Chain Deposition Disease (LCDD)

Clinical: - Myeloma-associated - Tubular + glomerular deposits (non-amyloid)

Pathology: - Light chain restricted - Linear (continuous) or granular - No fibrils

Treatment: hematologic therapy (similar to MM)

340.1.11.1 🩺 床邊速查

  • MCD: kids; foot process effacement; steroids
  • FSGS: adults US; APOL1; primary IS; secondary treat underlying
  • MN: older adults; anti-PLA2R; rituximab MENTOR
  • IgA: globally most; synpharyngitic hematuria; budesonide Nefecon
  • Lupus: ISN/RPS I-VI; MMF + steroids + voclosporin + belimumab
  • ANCA: pauci-immune; rituximab + steroids + avacopan
  • Anti-GBM: plasmapheresis + cyclophosphamide + steroids
  • MPGN/C3G: complement-mediated; iptacopan
  • DKD: 4 pillars (ACE/ARB + SGLT2i + finerenone + GLP-1)
  • AL amyloid: daratumumab + CyBorD (ANDROMEDA)