Membranous nephropathy Secondary causes: Epithelial malignancies, SLE, drugs (penicillamine), infections (Hep B, syphilis, malaria), metabolic (diabetes, thyroiditis) etc. Outcome: Progress irreversible in 70-90% (period variable), with onset of sclerosis, chronic renal failure, hypertension. Renal vein thrombosis is a well known complication.

Acute Proliferative Glomerulonephritis Commonly occurs 1-2 weeks after streptococcal throat or skin infection, often in children. Abrupt onset of acute nephritis with fever, nausea, oliguria, hematuria (coca-cola urine). Proteinuria, edema (periorbital puffiness), hypertension. Urine shows RBC casts along with WBC casts.

Acute Proliferative Glomerulonephritis Nephritogenic strains of Gp A ß hemolytic streptococci types 12, 4 & 1 Immune mediated disease - Immune complex disease / planted antigens. Cytoplasmic antigen endostreptosin and other cationic streptococcal antigens are found in glomeruli. Majority of patients have elevated ASLO and low complement

Gross: Enlarged, edematous Cortical surface congested with petichiae

Microscopy Primarily glomerular pathology Glomeruli enlarged, hypercellular, bloodless. Diffuse proliferation of endothelial cells, mesangial cells and epithelial cells Infiltration by neutrophils and monocytes Capillary lumina are obliterated Interstitial edema and inflammation Red cell casts in tubules

Immunofluorescence Granular deposits of IgG and Complement along basement membrane (lumpy - bumpy) and in mesangium

Clinical course 95% cases resolve spontaneously or with conservative therapy. Histological abnormalities disappear in about 4-6 weeks. Small minority (1%) show worsening and development of RPGN Another 1-2% show slow progression to chronic renal disease Prognosis is less favorable in adults

Acute non-streptococcal GN Staphylococcal endocarditis Pneumococcal pneumonia Meningococcemia Viral diseases (hepatitis B, mumps, varicella, EBV) Parasitic (malaria, toxoplasma)

Rapidly Progressive Glomerulonephritis Clinicopathological syndrome with rapid deterioration of renal function resulting in renal failure in weeks or months Characterized histologically by presence of Crescents in glomeruli

Rapidly Progressive Glomerulonephritis Post-infectious Systemic diseases - SLE, Goodpasture, Vasculitis, Cryoglobulinemia Idiopathic

Goodpasture’s Syndrome Acute fulminant disorder Pulmonary hemorrhages Rapidly progressive glomerulonephritis Pulmonary involvement precedes renal, with acute focal necrosis of alveolar walls and intra-alveolar hemorrhages. Anti-glomerular basement antibody also cross reacts with alveolar basement membrane. Goodpasture antigen is in the non-collagenous part of Collagen IV

Goodpasture’s Syndrome Triggering factors Hydrocarbons - paints and dyes Drugs - rifampicin Gasoline vapors Cigarette smoking has permissive effect. High prevalence of HLA DRW2 haplotype

Goodpasture’s Syndrome Crescents are seen in well established cases Formed by proliferation of parietal epithelial cells and infiltration by inflammatory cells Compress and destroy capillaries Fibrin is universally present Progress from cellular to fibrous crescents EM shows characteristic disruptions of basement membrane