Dr Ian Roberts Oxford Oxford Pathology Course 2010 for FRCPath
Present the basic diagnostic features of the commonest conditions causing renal failure Highlight diagnostic pitfalls.
Crescentic GN: renal vasculitis anti-gbm disease Acute tubular damage: ischaemic severe IgA, post-infectious, lupus, etc drugs crystal obstruction haemoglobinuria, myoglobinuria Acute tubulointerstitial nephritis Thrombotic microangiopathy: HUS accelerated hypertension scleroderma
pattern of disease IH Vasculitic focal segmental, necrosis-sclerosis pauci-immune Anti-GBM disease diffuse global, synchronous linear IgG &C3 Other GNs as for non-crescentic forms
Pauci-immune; focal segmental necrosis, proliferation and sclerosis
May be isolated renal vasculitis or associated with systemic vasculitis. Common association with pulmonary haemorrhage (Goodpasture s syndrome). 80% are ANCA-positive c-anca (anti-pr3): lesions are of similar age p-anca (anti-mpo): lesions typically at various stages from acute necrotising to fibrotic Histology of ANCA-negative cases is the same as the ANCA-positive
Arteritis (approx. 20%)
European vasculitis study group: Best histological predictors of long term renal function: % normal glomeruli, glomerulosclerosis, interstitial fibrosis, tubular atrophy. Best predictors of improvement of renal function from 0-18 months: % crescents, necrosis, interstitial inflammation. Hauer et al. Kidney Int 2002;62:1732-42
Autoantibodies to the Goodpasture antigen on the alpha 3 chain of type IV collagen Rapidly progressive GN +/- pulmonary haemorrhage Glomerular lesions typically diffuse, global & synchronous.
Autoantibodies to the Goodpasture antigen on the alpha 3 chain of type IV collagen Rapidly progressive GN +/- pulmonary haemorrhage Glomerular lesions typically diffuse, global & synchronous.
Linear IgG in glomerular basement membranes. Up to 32% of patients with anti- GBM antibodies also have positive ANCA (usually anti-mpo)
Interstitial oedema and an infiltrate of neutrophils. Neutrophilic tubulitis and neutrophil casts in tubules.
Syndromes of diffuse endothelial injury/activation resulting in: Glomeruli: Thrombosis leaky endothelium & widened sub-endothelial space splitting of basement membrane Arteries & arterioles: Thrombosis fibrin and red cell exudate within the intima proliferative intimal response
Haemolytic uraemic syndrome diarrhoeal, non-diarrhoeal Accelerated hypertension Scleroderma crisis Antiphospholipid antibody syndrome (+/- lupus) Drugs & irradiation HIV Thrombotic thrombocytopenic purpura Humoral rejection of allografts
Arterial - acute
Arterial - chronic
Glomerular - acute
Glomerular - chronic
Glomerular changes secondary to arterial
Role of the renal biopsy Di n n i n o sn i o g D D n D a o Do f o 1sasn n 1sasn D Di n n i D sd g1td g D 1 n n D s oi 1 g o Ta go Dn. T D sd g1td ns n D a gi Di no o i D D 1 agi Di n n i gg 1 o n f o 1i. gs1 n g ot i s o go g 1 1 n i Dn n. gi D 1 n i Dn M go g 1 gi n n os s1 g og
Role of the renal biopsy gi n 1 s n oi o o i 1i T i o n na i g n D 1 sn so o a oo D i 1. Do g n n1 o1t i g D oi sd i D o i D Dominant lesions in: Accelerated hypertension arteries Scleroderma crisis arteries HUS-D+ glomerular capillaries HUS-D- arteries TTP arterioles-glomerular hilum