SEARCH RESULTS FOR: Membranous-Nephropathy

Membranous Nephropathy

Authors: Jessica Krahn Membranous Nephropathy: Pathogenesis and clinical findings Reviewers: Brooke Fallis, Yan Yu*, Juliya Hemmet* * MD at time of publication Primary (Idiopathic) Membranous Nephropathy Secondary Membranous Nephropathy Drugs, infections, auto-immune diseases, and malignancies make antigens Blood tests for Anti- PLA2R antibodies are positive in ~70% of cases Autoantibodies are made to antigens expressed near or on podocyte surfaces or planted in the glomerular capillary wall (ie. PLA2R; THSD7A; NELL-1) IgG antibodies filter through the glomerulus Autoimmune: (e.g. Systemic Lupus Erythematous, thyroiditis) Drugs: (e.g. NSAIDs, gold, penicillamine, captopril) Malignancies: (ie. Prostate, Colon) Infections: (e.g. Hepatitis B, Syphilis) Circulating antigens filter through the glomerulus and between the GBM and podocytes Antibodies & antigens form immunocomplexes, which lodge Immunofluorescence shows diffuse “granular” between the glomerular basement membrane & podocytes deposits of immunocomplexes throughout GBM Basement membrane is formed between and around immunocomplex deposits Immunocomplexes activate complement and the assembly of the Membrane attack complex (MAC) MAC creates holes in podocyte plasma membranes Stimulates the release/activation of proteases and oxidases from glomerular podocytes and mesangial cells GBM appears thick on light microscopy “Spike and dome” pattern appears with silver stain Podocyte effacement Damage to negatively charged foot processes damages the charge barrier of the glomerulus that repels negatively charged molecules Increased filtration of large negatively charged molecules, especially albumin Induces ↑ hepatic lipoprotein synthesis and ↓ lipoprotein catabolism Hyperlipidemia (↑ serum LDL, VLDL, and triglycerides) ↑ lipid filtration through glomerulus Lipiduria (fatty casts) *Hypo-albuminemia ↓ oncotic pressure in capillaries Fluid leaks into interstitial space ↑ Filtration of Proteins C and S and antithrombin Hypercoagulable state Thrombosis *Edema (especially *Proteinuria ↑ Filtration of immunoglobulins Immunosuppression Infections ↑ Filtration of Plasminogen Plasminogen converted to plasmin in the cortical collecting duct via urokinase- type plasminogen activator Plasmin activates the epithelial sodium channel ↓ intravascular volume Hypotension Pre-Renal Acute Kidney Injury Underfill edema (see slide) peri-orbital, scrotal, labial, and extremities) Overfill edema (see slide) ↑ Na+ and water reabsorption Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published MONTH, DAY, YEAR on www.thecalgaryguide.com