Acute Renal Failure Terry Cook Imperial College London

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  • Slide 1
  • Acute Renal Failure Terry Cook Imperial College London
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  • Acute Renal Failure Rapid loss of glomerular filtration and tubular function leading to abnormal water, electrolyte and solute balance Occurs over hours to days Usually associated with oliguria. Some patients develop non-oliguric ARF eg. After radiocontrast media Acute-on chronic renal failure
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  • Aetiology of ARF Pre-renal Renal Glomerular Tubulointerstitial Vascular Post-renal
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  • Aetiology of ARF Glomerular RPGN Tubulointerstitial Acute tubular necrosis Acute tubulointerstitial nephritis Infection Cast nephropathy Vascular Thrombotic microangiopathy Cholesterol emboli Vasculitis
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  • Rapidly Progressive Glomerulonephritis (RPGN) RPGN is a clinical term for clinical manifestations that suggest severe crescentic glomerulonephritis Crescentic glomerulonephritis may be used for glomerulonephritis with any crescents but WHO suggests >50%
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  • Crescentic glomerulonephritis Crescents are an indication of severity of glomerulonephritis rather than its cause Complete pathological diagnosis requires analysis of immunofluorescence, electron microscopy and serology
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  • Natural history of crescents Breach in integrity of GBM ROS, proteases etc from inflammatory cells Cells and fibrin in Bowmans space Accumulation of macrophages and proliferating epithelial cells Apoptosis of cells and laying down of collagen Fibrocellular crescents and fibrous crescents
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  • Causes of crescentic glomerulonephritis Anti-GBM disease Immune complex disease Pauci-immune
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  • Frequency of types of crescentic GN Any Crescents >50% crescents Arteritis in Biopsy Anti-GBM5%11%3% Immune complex 49%29%14% Pauci- immune 47%61%84% After Jenette and Falk
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  • Frequency of types of crescentic GN Age (years) 10-1920-3940-64>65 Anti-GBM 15%24%2%11% Immune complex 50%48%30%8% Pauci- immune 35%28%69%82%
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  • Crescent formation in different glomerular diseases Patients with any crescents Patients with >50% crescents Anti-GBM disease9581 Pauci-immune (ANCA-associated)9048 Lupus GN (class III and IV)4011 Henoch-Schonlein purpura535 IgA nephropathy275 Postinfectious GN253 Fibrillary GN207 Type I membranoproliferative GN203
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  • Crescentic GN Differential diagnosis Light microscopy Immuno- fluorescence Other Anti-GBMSynchronous crescents Linear IgG and C3 Circulating anti-GBM antibody Pauci-immune Focal and segmental necrosis +/- vasculitis ScantyANCA Immune complex Focal and segmental or global hypercellularity Various e.g lupus serology, cryoglobulins etc
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  • Anti-GBM disease Presents with RPGN often accompanied by lung haemorrhage Rare disorder (1 pmp) predominantly in Caucasian populations Characterised by circulating and deposited anti-GBM antibodies
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  • Immune complex crescentic GN ImmunofluorescenceElectron microscopyClinical Lupus WHO Class III or IVFull HouseDeposits at all sites Tubulo-reticular bodies Serology, anti-C1q etc Henoch Schonlein purpuraIgA, C3Mesangial +/- capillary wall deposits Rash, arthralgia, abdominal pain IgA nephropathyIgA, C3Mesangial +/- capillary wall deposits History of sore throat Membranoproliferative GN Type I Capillary wall C3 +/- others Subendothelial deposits Double contours Infections eg. Hep C Cryoglobulins Post-infectious GNCapillary wall C3 +/- IgG humpsASOT Fibrillary GNMesangial IgG, C3Fibrils
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  • Pauci-immune crescentic GN Basic lesion is focal and segmental necrosis Often associated with vasculitis either in kidney or elsewhere
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  • Pauci-immune crescentic GN - syndromes 1.Limited to kidney 2.Microscopic polyangiitis necrotizing vasculitis in other systems including skin, mucous membranes, lungs, brain, gastrointestinal tract and muscle 3.Wegeners granulomatosis similar lesions to microscopic polyangiitis together with necrotizing granulomas of the upper and lower respiratory tract 4.Churg-Strauss syndrome history of asthma or allergic rhinitis and blood eosinophilia N.B. These syndromes cannot be distinguished on the basis of renal histology
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  • ANCA in small vessel vasculitis IIF pattern:C-ANCAP-ANCA Antigen:Proteinase 3Myeloperoxidase Syndromes:WG,MPMP, renal-limited vasculitis
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  • Clinical studies of ANCA Specific and sensitive marker for systemic vasculitis ANCA pattern and specificity correlate with clinical features Levels correlate with disease activity and extent Rising levels predict relapse
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  • European Vasculitis Study Group biopsy findings Biopsies from 96 patients with ANCA- associated vasculitis and creatinine
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  • European Vasculitis Study Group biopsy findings Predictors for GFR 0 %normal glomeruli %glomeruli with crescents Extent of tubular atrophy and interstitial fibrosis
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  • European Vasculitis Study Group biopsy findings Predictors for CORGFR 18 % glomeruli with fibrinoid necrosis % glomeruli with cellular crescents Tubulointerstitial inflammation Tubular atrophy and interstitial fibrosis did not predict CORGFR 18 even though they correlated with GFR 18 implying that this was dependent on GFR 0
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  • European Vasculitis Study Group biopsy findings In ANCA GN the best histological predictors of long-term renal function are Normal glomeruli, glomerulosclerosis, interstitial fibrosis and tubular atrophy The best predictors of the improvement in renal function from 0 to 18 months are Crescents, fibrinoid necrosis and interstitial inflammation
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  • Acute tubular necrosis Prolonged hypoperfusion Drugs NSAIDs, ACE inhibitors Direct toxicity Drugs eg. Aminoglycosides, cisplatin Radiocontrast agents Haem pigments Snake venom Heavy metals lead, mercury Associated with nephrotic syndrome
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  • Acute tubular necrosis Tubular dilatation Loss of brush border Epithelial cell vacuolation Detachment of epithelial cells Granular casts Hyperchromasia of tubular nuclei Mitoses Calcification Interstitial oedema Interstitial inflammation Nucleated rbcs in vasa recta
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  • Acute tubulointerstitial nephritis Infectious eg. HIV, BKV, fungi, TB Drugs Post infectious SLE ANCA associated With uveitis (TINU)
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  • Acute tubulointerstitial nephritis Interstitial infiltrate of mononuclear cells Mainly T cells and macrophages Tubulitis +/- eosinophils May rarely be anti-TBM antibodies
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  • Granulomatous tubulointerstitial nephritis Infectious Sarcoidosis Drugs Idiopathic
  • Slide 30
  • Myeloma Cast Nephropathy Light chains precipitate in tubules Casts are large and eosinophilic may be fractured or fragemented Multinucleate giant cells my be found adjacent to casts In some cases the casts may stain for amyloid Interstitium typically shows an infiltrate of lymphocytes and macrophages
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  • Thrombotic microangiopathy Haemolytic-uraemic syndrome Infection particularly verotoxin-producing E. coli Drugs CNIs, mitomycin Transplant rejection Antiphospholipid antibodies Post-partum Factor H deficiency Bone marrow transplantation Thrombotic thrombocytopenic pupura Malignant Hypertension Scleroderma
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  • Thrombotic microangiopathy Glomeruli Thrombosis Trapped fragmented rbc Thickened capillary walls with subendothelial fibrin Ischaemic changes Arterioles fibrinoid Interlobular arteries loose intimal thickening
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  • Cholesterol emboli Common cause of unexplained renal failure in elderly Predisposing factors Trauma eg catheterisation, surgery Anticoagulation Spontaneous May be slowly progressive May involve glomeruli