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Lecture 3. Secondary glomerular diseases and diseases of large blood vessels Crescentic Glomerulonephritis and Vasculitis • • • • VASCULITIS: Inflammation and necrosis of blood vessels Large vessel vasculitis eg Giant cell (Temporal) arteritis Medium sized vessel arteritis eg Polyarteritis Nodosa Small vessel vasculitis* – *Capillaries, venules, arterioles +/- small arteries – Skin only e.g. drugs – Multiple organs, tissues, kidney: systemic vasculitis • Crescentic glomerulonephritis is typical of systemic vasculitis involving the kidney • (renal-limited crescentic GN also occurs) Vasculitis Vasculitis - artery in Polyarteritis Nodosa Lumen Crescentic Glomerulonephritis, vasculitis C R E S C E N T Glom • Crescent: Proliferation of cells inside Bowman’s capsule obliterates urinary space Systemic small vessel Vasculitis • Microscopic polyangiitis (micro PAN) – Vasculitis in small, med blood vsls; glomerulonephritis • Wegener’s granulomatosis – Necrosis and granulomas in upper/lr resp tract – Vasculitis in small, med blood vsls; glomerulonephritis • Henoch-Schlonlein purpura • Cryoglobulinemia • Goodpasture’s syndrome and anti-GBM nephritis – Anti-GBM, anti-alveolar BM antibodies – Pulmonary haemorrhage, glomerulonephritis Wegener’s granulomatosis • Multinucl Giant cell • Granulomas, necrosis, vasculitis in respiratory tract • Crescents, focal necrosis in glomeruli Vasculitis - clinical • Clinical signs vary: Fever, rash, arthralgias, pulmonary infiltrates or nodules, haemorrhage, ENT, GI, musculoskel or neurological symptoms, • Acute renal failure, oliguria over wks, months (dialysis); hypertension, haematuria, proteinuria • Investigations: Renal function, imaging, ESR, serology, ANCA Anti-neutrophil cytoplasmic antibodies (ANCA) • Serum antibodies to enzymes in neutrophil granules, monocyte lysosomes • Immunofluorescence: Cytoplasmic or Perinuclear • P-ANCA (anti-myeloperoxidase) in 80% of micro polyangiitis; more often indolent, renal limited • C-ANCA (anti-proteinase 3) in 90% of Wegener’s • Very useful in diagnosis; follow up of disease activity in Wegener’s with C-ANCA Crescentic GN, vasculitis • Crescent N Cr • Necrosis and crescent Crescentic GN, vasculitis: Immunofluorescence findings . .. ,. 65% “pauci-immune” – pauci = few or no IC • 20% immune complex • 15% anti-GBM Crescentic GN, vasculitis - pathology • LM: Glomerular crescents, inflammation and necrosis • Crescent: Proliferation of cells inside Bowman’s capsule obliterates urinary space (-> oliguria) • Focal glomerular inflammation, necrosis – Immune complex deposits FM & EM 20% e.g. SLE, cryoglob – anti-GBM 15% Goodpature’s syndrome, anti-GBM nephritis – pauci-immune 65% (in ANCA+ microscopic polyangiitis, Wegener’s) – Adverse prognosis: >80% crescents, anti-GBM • Summary: Crescentic GN typical of systemic small vessel vasculitis; sometimes limited to kidney Secondary glomerular diseases • Glomerular disease an important feature of multisystem diseases - vasculitis, diabetes, SLE, amyloidosis • DIABETES MELLITUS – Relative/absolute deficiency of insulin secretory response; leading cause of end-stage renal disease in US, Europe (40%) – Type 1: autoimmune destruction of insulin secreting beta cells – Type 2 (90%) decreased insulin secretion; insulin resistance • Gradual onset of proteinuria, glycosylation of proteins, microangiopathy thick leaky GBM, and increased mesangial matrix synthesis; also suscept to pyelonephritis Glomerular and vascular lesions in Diabetes Art Art Art KW SLE (Lupus) nephritis SLE (Lupus) nephritis • Chronic auto-immune disease; females 20-30 yrs • Rash, connective tissues, kidney etc • Antinuclear (e.g. anti-ds DNA), anticytoplasmic & antiphospholipid antibodies • Lupus nephritis in 90% - variable proteinuria, haematuria • Immune Complex Glomerulonephritis ranges from very mild to severe • Glomerulonephritis a major cause of morbidity, mortality Lupus nephritis Amyloidosis • Abnormal beta-fibrillar protein (15 classes) • (A-beta in Alzheimer’s) • AA amyloid (chronic infection, inflammation) or AL amyloid (Ig derived) deposited in glomeruli, renal vessels • Proteinuria • Poor prognosis Amyloidosis Clinical Presentations of glomerular disease Clinical Presentations of glomerular disease • CRESCENTIC GN and VASCULITIS (“Rapidly progressive GN”) • HAEMATURIA – IgA nephropathy • PROTEINURIA & NEPHROTIC SYNDROME – Minimal change disease – Membranous glomerulonephritis – SLE, diabetes, renal amyloidosis • ACUTE NEPHRITIS – Post-streptococcal glomerulonephritis • Haematuria, hypertension, raised serum creatinine, oedema • Immune complexes to streptococcal antigen • Most patients recover fully • CHRONIC RENAL FAILURE – Abnormal renal function tests. Raised se Cr, reducd Cr Cl & clinical signs – Develops slowly, chronically over years – Glomerular disease not the only cause (nephrosclerosis, APCKD) Lesions of large blood vessels Lesions of Renal Blood Vessels • Thrombi, emboli, infarcts – Renal artery thrombosis – Left heart, heart valves e.g. mitral vegetations – Atheroemboli from aorta -> interlobular arteries in kidneys Lesions of Renal Blood Vessels • Vasculitis (other than small vessel vasculitis) – – – – Large and medium sized blood vessels, small arteries. Temporal (Giant cell) arteritis - head and neck Takayasu’s - coronaries (Vasculitis a/w infection include fungal) • Polyarteritis Nodosa – aneurysms in coeliac, mesenteric, coronary and renal arteries; hepatitis B in 30%; ANCA negative Lesions of Renal Blood Vessels • Renal artery stenosis – Proximal renal artery atherosclerosis – Fibromuscular dysplasia – GFR afferent arteriole pressure -> Renin, BP • Nephrosclerosis – Age change worsened by hypertension – Thick arterioles (“hyaline” arteriolosclerosis) & thickened small, medium sized arteries – Small kidneys, granular suface +/- larger scars • Malign BP and thrombotic microangiopathies – Endothelial injury, necrosis of media, thrombi Nephrosclerosis • Granular renal cortical surface & scars • Thickened artery