Transcript SLE - ACR criteria 1982

Acute Renal Failure
Terry Cook
Imperial College London
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
Aetiology of ARF
• Pre-renal
• Renal
– Glomerular
– Tubulointerstitial
– Vascular
• Post-renal
Aetiology of ARF
• Glomerular
– RPGN
• Tubulointerstitial
–
–
–
–
Acute tubular necrosis
Acute tubulointerstitial nephritis
Infection
Cast nephropathy
• Vascular
– Thrombotic microangiopathy
– Cholesterol emboli
– Vasculitis
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%
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
Natural history of crescents
Breach in integrity of GBM
– ROS, proteases etc from inflammatory cells
Cells and fibrin in Bowman’s space
Accumulation of macrophages and proliferating epithelial cells
Apoptosis of cells and laying down of collagen
Fibrocellular crescents and fibrous crescents
Causes of crescentic
glomerulonephritis
• Anti-GBM disease
• Immune complex disease
• Pauci-immune
Frequency of types of crescentic GN
Any
Crescents
>50%
crescents
Arteritis in
Biopsy
Anti-GBM
5%
11%
3%
Immune
complex
49%
29%
14%
Pauciimmune
47%
61%
84%
After Jenette and Falk
Frequency of types of crescentic GN
Age (years)
10-19
20-39
40-64
>65
Anti-GBM
15%
24%
2%
11%
Immune
complex
50%
48%
30%
8%
Pauciimmune
35%
28%
69%
82%
Crescent formation in different glomerular diseases
Patients with
any crescents
Patients with
>50%
crescents
Anti-GBM disease
95
81
Pauci-immune (ANCA-associated)
90
48
Lupus GN (class III and IV)
40
11
Henoch-Schonlein purpura
53
5
IgA nephropathy
27
5
Postinfectious GN
25
3
Fibrillary GN
20
7
Type I membranoproliferative GN
20
3
Crescentic GN – Differential diagnosis
Light
microscopy
Immunofluorescence
Other
Anti-GBM
Synchronous
crescents
Linear IgG and
C3
Circulating
anti-GBM
antibody
Pauci-immune
Focal and
segmental necrosis
+/- vasculitis
Scanty
ANCA
Immune
complex
Focal and
segmental or
global
hypercellularity
Various
Various
e.g lupus serology,
cryoglobulins etc
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
Immune complex crescentic GN
Immunofluorescence
Electron microscopy
Clinical
Lupus WHO Class III or IV
“Full House”
Deposits at all sites
Tubulo-reticular bodies
Serology, anti-C1q etc
Henoch Schonlein purpura
IgA, C3
Mesangial +/- capillary
wall deposits
Rash, arthralgia,
abdominal pain
IgA nephropathy
IgA, C3
Mesangial +/- 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 GN
Capillary wall C3 +/IgG
“humps”
ASOT
Fibrillary GN
Mesangial IgG, C3
Fibrils
Pauci-immune crescentic GN
• Basic lesion is focal and segmental
necrosis
• Often associated with vasculitis either in
kidney or elsewhere
Pauci-immune crescentic GN syndromes
1.
2.
3.
4.
Limited to kidney
Microscopic polyangiitis – necrotizing vasculitis in other
systems including skin, mucous membranes, lungs, brain,
gastrointestinal tract and muscle
Wegener’s granulomatosis – similar lesions to microscopic
polyangiitis together with necrotizing granulomas of the upper
and lower respiratory tract
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
ANCA in small vessel vasculitis
IIF pattern:
Antigen:
Syndromes:
C-ANCA
Proteinase 3
WG,MP
P-ANCA
Myeloperoxidase
MP, renal-limited vasculitis
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
European Vasculitis Study Group biopsy
findings
• Biopsies from 96 patients with ANCAassociated vasculitis and creatinine
<500 mmol/l
• Studied
– GFR0 – GFR at presentation
– GFR18 – GFR at 18 months
– CORGFR18 – GFR at 18 months
corrected for GFR0
European Vasculitis Study Group
biopsy findings
• Predictors for GFR0
– %normal glomeruli
– %glomeruli with crescents
– Extent of tubular atrophy and interstitial
fibrosis
European Vasculitis Study Group
biopsy findings
• Predictors for CORGFR18
– % glomeruli with fibrinoid necrosis
– % glomeruli with cellular crescents
– Tubulointerstitial inflammation
• Tubular atrophy and interstitial fibrosis did
not predict CORGFR18 even though they
correlated with GFR18 implying that this
was dependent on GFR0
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
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
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
Acute tubulointerstitial nephritis
•
•
•
•
•
•
Infectious eg. HIV, BKV, fungi, TB
Drugs
Post infectious
SLE
ANCA associated
With uveitis (TINU)
Acute tubulointerstitial nephritis
• Interstitial infiltrate of mononuclear cells
– Mainly T cells and macrophages
• Tubulitis
• +/- eosinophils
• May rarely be anti-TBM antibodies
Granulomatous
tubulointerstitial nephritis
•
•
•
•
Infectious
Sarcoidosis
Drugs
Idiopathic
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
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
Thrombotic microangiopathy
• Glomeruli
–
–
–
–
Thrombosis
Trapped fragmented rbc
Thickened capillary walls with subendothelial fibrin
Ischaemic changes
• Arterioles – fibrinoid
• Interlobular arteries – loose intimal thickening
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