Transcript Kidney-lect-06-09-3

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