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

• Crescent: Proliferation of cells inside Bowman’s capsule - obliterates urinary space

Glom

CRESCENT

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

• Necrosis and crescentN

Cr

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

KW

Art

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