Glomerulonephritis Study Guide

📖 Core Concepts Glomerulonephritis (GN): A group of kidney diseases that damage the glomeruli (filtering units) of both kidneys; may be inflammatory or non‑inflammatory. Nephrotic vs. Nephritic syndrome Nephrotic: Massive protein loss → hypoalbuminemia → edema, hyperlipidemia, lipiduria. Nephritic: Hematuria with RBC casts, oliguria, hypertension, mild‑moderate proteinuria. Proliferative vs. Non‑proliferative GN Proliferative: ↑ cellularity, usually nephritic, rapid progression possible. Non‑proliferative: No cellularity rise, often nephrotic, slower course. Primary vs. Secondary GN Primary: Intrinsic kidney disease (e.g., Minimal Change, IgA). Secondary: Result of infection, drugs, systemic disease (e.g., lupus, diabetes). 📌 Must Remember Minimal Change Disease → podocyte foot‑process fusion; steroid‑responsive; common in children. Focal Segmental Glomerulosclerosis (FSGS) → segmental sclerosis; steroids help but 50% progress. Membranous GN → anti‑PLA₂R antibodies (≈2/3); “spike and dome” IgG granules; 1/3 remit, 1/3 stable, 1/3 progress. IgA Nephropathy → most common GN; mesangial IgA deposits; often follows URTI. Post‑infectious GN → 1–4 wk after Strep pyogenes throat infection; low complement; children recover spontaneously. MPGN Types Type 1: immune‑complex subendothelial deposits; low C3. Type 3: subepithelial deposits. Rapidly Progressive GN (RPGN) → crescents on biopsy; three types: Type 1 (Goodpasture): anti‑GBM antibodies, linear IgG, pulmonary hemorrhage. Type 2: immune‑complex (lupus, IgA). Type 3: pauci‑immune, ANCA‑associated vasculitis. Key labs: urinalysis (RBC casts, protein), complement C3/C4, ASO titre, anti‑GBM, ANCA, ANA. First‑line therapy: corticosteroids for most primary & many proliferative forms; add cyclophosphamide, plasmapheresis, or other immunosuppressants for RPGN. 🔄 Key Processes Pathogenesis of Nephritic Syndrome Immune complex deposition → complement activation → glomerular inflammation → reduced GFR → ↓ renal perfusion → renin‑angiotensin activation → hypertension. Nephrotic Edema Formation Proteinuria → hypoalbuminemia → ↓ plasma oncotic pressure → fluid shifts to interstitium → secondary sodium & water retention via RAAS → edema. Crescent Formation in RPGN Fibrin leakage → proliferation of parietal epithelial cells + monocyte influx → crescent encircles Bowman's capsule → rapid loss of filtration surface. 🔍 Key Comparisons Minimal Change vs. FSGS MCD: Light microscopy normal, EM foot‑process fusion, steroid‑responsive, excellent prognosis. FSGS: Segmental sclerosis on LM, variable EM changes, steroids partially effective, higher risk of CKD. IgA Nephropathy vs. Post‑Infectious GN IgA: Mesangial IgA deposits, often after URTI, chronic course. Post‑Infectious: Subepithelial “humps”, low C3, self‑limited in children. Type 1 MPGN vs. Type 3 MPGN Type 1: Subendothelial deposits → “tram‑track” on LM; associated with lupus, hepatitis. Type 3: Subepithelial deposits → more membranous‑like appearance. ⚠️ Common Misunderstandings “All GN causes hematuria” – Non‑proliferative forms (e.g., Minimal Change) often present with pure proteinuria, no hematuria. “Steroids cure all GN” – Effective for Minimal Change and many proliferative forms, but FSGS, MPGN, and RPGN often need additional agents. “Low complement = post‑infectious GN only” – Low C3 also seen in MPGN and lupus‑related GN. 🧠 Mental Models / Intuition “Inflammation → nephritic; permeability → nephrotic.” Think cellular infiltration = blood in urine; podocyte leak = protein in urine. “Crescent = rapid decline” – Any biopsy showing crescents flags an urgent need for aggressive immunosuppression. 🚩 Exceptions & Edge Cases Thin Basement Membrane Disease: Presents with microscopic hematuria but normal complement and no proteinuria; benign course. Membranous GN: A third of patients achieve remission spontaneously; not all need aggressive immunosuppression. ANCA‑negative pauci‑immune RPGN: May occur; diagnosis relies on histology and clinical picture rather than serology alone. 📍 When to Use Which Steroid monotherapy → Minimal Change, early IgA, early post‑infectious (children). Steroid + cyclophosphamide → RPGN types 1 & 2, severe FSGS, MPGN with rapid decline. Plasmapheresis → Goodpasture (anti‑GBM) and severe ANCA‑RPGN. Supportive care only → Thin basement membrane disease, mild post‑infectious GN in children. 👀 Patterns to Recognize Post‑infectious GN: 1–4 wk lag after streptococcal infection + low C3 + “hump” deposits. Goodpasture: GN + pulmonary hemorrhage + linear IgG on IF. ANCA‑associated RPGN: Rapid loss of function, pauci‑immune IF, systemic vasculitis signs (e.g., sinusitis, skin lesions). 🗂️ Exam Traps Choosing “IgA nephropathy” for a patient with low complement – IgA usually has normal complement; low C3 points to MPGN or post‑infectious. Assuming all nephrotic syndromes are immune‑mediated – Minimal Change is steroid‑responsive but not immune‑complex driven. Selecting “biopsy not needed” for adult post‑infectious GN – Adults often require biopsy because prognosis is poorer and alternative diagnoses are common. Confusing “spike and dome” with “tram‑track” – Spike‑dome = membranous (subepithelial immune deposits); tram‑track = MPGN (double contour of GBM). --- Quick Review Tip: Memorize the 4‑column table – Disease | Typical presentation (nephrotic vs nephritic) | Key pathology (LM/IF/EM) | First‑line therapy. This consolidates most exam questions in one glance.