Glomerulonephritis Flashcards
Goodpasture’s
a) Typical history
b) CXR features
c) Renal biopsy features
d) Antibodies and target
e) Management
f) Chances of recovery
a) Usually males 20-30, start with respiratory tract infection (cough, SOB), followed by haemoptysis, then proteinuria/haematuria (often become anuric)
b) Patchy infiltrates (alveolar haemorrhage), often have bilateral creps o/e
c) Crescentic glomerulonephritis, and characteristic linear IgG staining on immunofluorescence
- If active crescents with minimal scarring this indicates better chance of recovery with treatment (steroids, cyclophosphamide, PLEX)
d) 90% have anti-GBM antibodies directed towards alpha-3 chain of type IV collagen
e) High dose steroids, cyclophosphamide (+ PLEX if pulmonary-renal syndrome)
f) - 20% mortality
- Most with Cr >600 or anuria will not regain renal function
Nephrotic syndrome
a) Triad and other biochemistry
b) Normal, abnormal + nephrotic range ACR/PCR/24h collection
c) A1-A3 in CKD
d) Complications
e) Who to biopsy?
f) Management
a) - Triad (HOP): hypoalbuminaemia, oedema, proteinuria
- Deficiency in anti-clotting factors - antithrombin III, protein S and C
- Raised fibrinogen
- Low thyroxine
- Raised lipids
b) Proteinuria defined as:
- ACR >30 mg/mmol (nephrotic range: >220), or
- Urine PCR >45 mg/mmol (nephrotic range: >300)
- Urine protein >150 mg per day
(nephrotic range: >3 g/day)
c) A1 <3
A2 3-30*
A3 >30**
d) - VTE due to antithrombin III deficiency. Renal vein thrombosis occurs in 40%
e) - All adults
- Children if recurrent/resistant cases
f) - Low salt and fluid intake
- Diuretics
- BP control
- Steroids in most cases (if more chronic and adult - may be ineffective)
- LMWH if albumin <20
- May require HAS/NaCl infusion
SLE
a) Lupus nephritis histology (note there are 6 types)
b) Immunology - bloods, antibodies, renal biopsy (vs. vasculitis)
a) Mild - mesangial hypercellularity
Severe - fulminant focal necrotising proliferative disease with crescent formation
Subendothelial immune complex deposits will be present
Most common is type IV - diffuse proliferative GN
b) Bloods - pancytopenia, raised CRP/ESR
Abs - IgG ANA (95%), anti-dsDNA, anti-Smith, APLS
C3 and C4 low
Biopsy - mesangial deposition of IgA, IgG, IgM, C3 and C4 (full house). Compared with pauci-immune (no immunoglobulin) deposition in vasculitic GN.
Complement - values interpretation
C3 alone is often decreased in infectious disease (sepsis, endocarditis, measles)
- Causes type 2 mesangiocapillary GN
C3 and C4 are often both decreased in immune complex disease (SLE, rheumatoid vasculitis, but not uncomplicated RA) and in chronic infection with Hep C.
- Causes type 1 mesangiocapillary GN (tramline appearance on biopsy)
C4 alone is characteristically decreased in angioedema and immune complex diseases (SLE, vasculitis, cryoglobulinaemia and cold agglutinin disease)
Post-strep GN
a) Biopsy findings
a) Subepithelial humps on electron microscopy
IgM, IgG and complement granular deposits
Membranous nephropathy
a) Biopsy findings
b) Causes
c) Presentation
d) Management
e) If sudden worsening of renal function, consider what cause?
a) - Subepithelial IgG (immune complex) and C3 deposits across entire GBM
- Causing thickened GBM with GBM ‘spikes’ (as opposed to subepithelial ‘humps’ in post-strep)
b) - Primary: PLA2R antibodies
- Secondary: cancer (20-30%), Hep B (e.g. IVDU), SLE, drugs (NSAIDs, gold, penicillamine), malaria
c) Nephrotic syndrome (proteinuria, oedema, etc.)
- Features of underlying disease
- 30% progress to ESRD
d) - Dietary sodium restriction
- Diuretics
- Prophylactic anticoagulation
- ACE inhibition
- If persistent proteinuria, rise in serum Cr <30% in 6-12 months or severe symptoms, consider immunosuppression (cyclophosphamide, ciclosporin)
e) Renal vein thrombosis (particularly if intercurrent infection)
HIV-associated nephropathy (HIVAN)
a) US findings
b) Biopsy findings
a) Large echogenic kidneys
b) FSGS - collapsed glomerular tuft, tubuloreticular strictures, ribonucleoprotein deposits
Focal necrotising crescentic nephritis
a) What are the 3 types and causes
b) What is a crescent?
c) What is classed as focal?
Typical of RPGN. 3 types:
- Type 1 = anti-GBM
- Type 2 = immune complex mediated (IgA, SLE, HSP, post-strep)
- Type 3 = pauci-immune (ANCA vasculitis, or idiopathic)
b) Crescent - two or more cell layers partially or totally filling the Bowman’s capsule
c) Focal = at least 50% normal glomeruli
Diabetic nephropathy
a) Pattern
b) Pathognomonic lesions
a) Nephrotic syndrome
- nodular sclerosis of glomeruli (different to FSGS)
b) Kimmelsteil-Wilson lesions - nodular nephropathy
IgA nephropathy (Berger’s disease)
a) Classical presentation (vs post-strep)
b) Risk factors
c) Biopsy findings (vs post-strep)
d) Management
a) - GN (haematoproteinuria) + very recent respiratory tract infection (post-strep has longer lead time e.g. few weeks)
- Young males (children more commonly post-strep)
- 10% progression to ESRD
b) Coeliac, HIV, cirrhosis, familial
c) Mesangioproliferative GN:
- Diffuse mesangial proliferation (mesangioproliferative*) and matrix expansion, with IgA deposits (IgA deposits much more numerous in IgA nephropathy vs post-strep GN)
- indistinguishable from HSP (lie on same spectrum of disease)
*also known as mesangiocapillary GN. Other cause includes Hep C
d) - Often just conservative management
- ACE inhibitors if high BP/ proteinuria/ renal dysfunction to slow progression to CKD/ESRF
- If progressive CKD, prednisolone
Alport syndrome
a) Clinical features
b) Inheritance
c) Management
d) Biopsy findings
a) - Progressive nephropathy (presents in childhood - haemato-proteinuria), 80% males have ESRF by age 40 (females affected less and more slowly)
- Sensorineural deafness (presents in late childhood)
- Ocular abnormalities (anterior lenticonus, dot and fleck retinopathy, corneal dystrophy)
b) - Mutation of type IV collagen (80%), causing defective basement membrane in the glomerulus, cochlea and eye
- X-linked recessive in 80% (so more common in males)
- 20% have AD or AR inherited mutation
- COL4A5 gene affected
c) ACE, diuretics
d) Basket weave appearance of the basement membrane
Minimal change disease
a) Cause in adults to be aware of
b) Findings on microscopy
c) Treatment
a) - Hodgkin lymphoma - usually improves with chemotherapy, if not give prednisolone
- NSAIDs can also cause it
b) Light microscopy - NAD
Electron microscopy - fused podocyte foot processes
c) High dose steroids
- As for other nephrotic - VTE prophylaxis
- As for other GN - BP control, monitor renal function
ANCA-associated vasculitis
a) c-ANCA - associated antibody and diseases
b) p-ANCA - associated antibody and diseases
c) Where there is GN, characteristic finding?
c-ANCA:
- Anti-PR3
- 90% of Wegener’s, 30% of MPA and Churg-Strauss
- Very rare in non-vasculitis
p-ANCA:
- Anti-MPO (sounds like MPA)
- 90% of MPA, 70% of Churg-Strauss, 20% of PAN, 10% of Wegener’s
- 30% Goodpasture’s have anti-MPO as well as anti-GBM
- Also associated with chronic infection, colitis and liver disease
c) Crescentic pauci-immune GN
GN quickfire
a) Hep B causes…
b) Hep C causes…
c) Hodgkin lymphoma causes…
d) IgA nephropathy causes…
e) SLE causes…
f) ANCA/GBM disease cause…
g) Diabetes causes…
h) HIV causes…
i) Most common histological appearances in adults
a) Membranous nephropathy (nephrotic)
b) Mesangioproliferative GN
c) Minimal change (nephrotic)
d) Mesangioproliferative GN
e) Diffuse or focal necrotising GN, or mesangioproliferative (with “full house” immune complex deposition)
f) Crescentic focal necrotising GN:
- anti-GBM with linear IgG deposition = type 1;
- ANCA-associated = pauci-immune type 3
g) Diabetic nephropathy - nephrotic
h) FSGS
g) FSGS (especially if older, hypertensive, and obese patients), then membranous. Most common in younger patients in minimal change
Holiday in Brazil, itchy skin rash and develops GN
a) Cause?
a) Schistosoma mansoni GN
