Glomerulonephritis

Glomerulonephritis

1. Immune mediated disorders-- inflammation within the glomerulus and other compartments of the kidney

   • 3rd Commonest cause of renal failure in Europe Commonest cause worldwide

2. Classification

   • Sites of injury-
     • GBM- Goodpastures Podocytes-Membranous Nephropathy
   • Infective VS Non-Infective
   • Primary VS Secondary
     • Primary GN -no associated disease elsewhere Post-infectious GN, IgA nephropathy, Anti-glomerular basement membrane (anti-GBM) GN, Idiopathic crescentic GN.
       • Hereditary nephritis /Alport Syndrome: Family history of progressive nephropathy. Sensorineural deafness. Ocular abnormalities- Anterior lenticonus, Defective BM in the glomerulus, cochlea, and eye, X-linked inheritance, Mutation in COL4A5 gene encoding α5 type IV collagen
     • Secondary GN- part of a systemic disease: SLE ,Henoch-Schonlein purpura, ANCA vasculitis, Cryoglobulinaemic vasculitis, Thrombotic microangiopathies, Deposition diseases (amyloidosis, light chain deposition disease), Malignancies (Hodgkin's lymphoma, lung and colorectal cancer).
       • Lupus nephritis: Common in Blacks, Hispanics and Asians, ANA and Anti –dsDNA, low C3 and C4, , Anti Ro and Anti La, Immunostaining of kidney biopsy positive for IgG, IgM, IgA, C3, C1q, Treatment – immunosuppression (steroids, cyclophosphamide, Rituximab, hydroxychloroquine
   • Histological appearance
     • Focal Vs Diffuse
     • Global vs Segemental

3. Clinical Presentation

   • Nephritic Syndrome
     • Haematuria Hypertension
     • Rapidly progressive/crescentric
       • Rapid onset- presenting as AKI Causes: Goodpastures, ANCA positive vasculitis
         • Goodpastures: Presents as Rapidly progressive GN +/- Pulmonary haemorrhage, More common in Caucasians, Antibodies (IgG) against alpha 3 chain of type 4 collagen, Histology –focal and segmental necrotizing, crescentic GN, Immunostaining - IgG, C3, EM frequent breaks in the BM, Treatment- plasma exchange, steroid, Cyclophosphamide
     • IgA Nephropathy/Bergers disease
       • Young adult haematuria following an URTI
       • Commonest cause of Primary GN in the world, 2nd and 3rd decades, Abnormal IGA deposition in the glomerulus, Mesangial Proliferation, Haematuria and proteinuria, Synpharyngetic haematuria
         • HSP presents as a tetrad of skin rash, abdo pain, arthralgia and nephriis)
   • Nephrotic Syndrome
     • Proteinuria Oedema Hypoalbuminemia
     • Minimal Change Disease
       • Children Causes:Hodgkin's, NSAIDs Treatment:Steroids
         • Less common in adults: Commonest cause of NS in children, Symptoms- oedema, proteinuria, hypotension, frothy urine, lipiduria, infections, Histology- normal on LM, effacement of podocyte foot process on EM
     • Membranous
       • Causes: Infection, rheumatoid drugs, malignancy
         • 1/3 resolve, 1/3 respond to cytotoxics, 1/3 CKD
     • Focal segmental glomerulosclerosis
       • idiopathic or secondary to HIV, heroin
   • Mixed nephritic/nephrotic presentation
     • Diffuse proliferative glomerulonephritis
       • classical post streptococcal glomerulonephritis in children
         • SLE
     • Membranoproliferative glomerulonephritis
       • 2 Types- 1 HepC 2 Lipodystrophy
   • CLINICAL FEATURES
     • Features of renal failure: Haematuria, Proteinuria, Oliguria with salt and water retention, Hypertension
     • Features of underlying disease: Sore throat, Skin Rash, Arthralgia, Fever, Weight loss, Diarrhoea, Haemoptysis, Malignancy
     • Features of uraemia: Nausea and vomiting, Altered consciousness, Chest pain, Anorexia

4. INVESTIGATIONS: Dipstick urine for haematuria, proteinuria, Urine microscopy for red morphology ± casts, Assess degree of proteinuria, Scr, eGFR, U&E, FBC, Bone Profile, LFT, Acute phase markers CRP and ESR, Immunological and serological screen, USS Kidneys, Renal Biopsy

   • Treatment
     • Supportive: Life Style modification , Salt and water restriction, Control BP (ACEI, ARB, BB, CCB diuretics, Nutrition, Treat infections, Electrolyte and Acid base balance, Renal replacement therapy
     • Definitive: Treat underlying cause eg infection, cancer, Immunosuppression eg Steroids, alkylating Agents etc, Plasmapheresis, Renal transplant