Glomerulonephritis Flashcards
What are features of nephritic syndrome?
Haematuria Dysmorphic red cells Red cell casts Hypertension Renal failure Pyuria Proteinuria
What are the classes of lupus nephritis
1 - minimal mesangial 2 - mesangial proliferation 3 - focal nephritis 4 - diffuse nephritis 5 - membranous nephritis 6 - sclerotic nephritis
What is a RPGN
Nephritic syndrome with rapidly progressive renal failure
Pathological equivalent is crescents
What are the 3 groupings of causes of RPGN
Immune complex mediated
Pauci-immune
Anti-GBM
What infections typically cause a PIGN (post infectious)
Strep pyogenes (impetigo, pharyngitis) Staph aureus
What is the time frame from infection to developing PIGN
Impetigo 2-6 weeks
Pharyngitis 1-3 weeks
What is the age distribution of anti-gbm disease
Males 20-30 - worse prognosis
age greater then 50 - females greater then males, don’t often present with good pastures
Pathology of anti-GBM disease
Auto-antibodies against collagen 4 (alpha 3 chain) in the basement membrane, usually IgG
Tests in post infectious GN
Low C3, normal C4
Test for strep (culture, ASOT, anti-DNase)
Rarely requires biopsy for diagnosis
Biopsy findings in post-infectious GN
Hypercellularity of mesangial and endothelial cells with neutrophil infiltrates
Sub epithelial humps, sub endothelial immune deposits of IgG, IgM, C3
How many of those with anti-GBM have goodpastures
30-40%
Treatment of anti-GBM
Daily plasmapheresis for 2-3 weeks
Oral steroids and cyclophosphamide
What are features of a nephrotic syndrome
Proteinuria (greater then 3.5g per 24hours) Hypoalbuminaemia Hypertension High cholesterol and lipiduria Hypercoagulable Odema/anasarca
Immunofluorescence findings in anti-GBM disease
Linear IgG deposition along basement membrane
Treatment of post infectious GN
Supportive, minimal need for immunosuppressive even with crescents
May need dialysis
Treat HTN and odema (ACE-I, dieretics)
Treat infection
Who does IgA typically occur in
Males, 20-30 years
White/Asians
Most common GN worldwide
Clinical presentation of IgA disease
- Recurrent episodes of macroscopic haematuria during or immediately after URTI
- Persistent asymptomatic microscopic haematuria
- RPGN with ARF
Treatment of IgA GN
Mild - ACEI
RPGN - steroids, immunosuppression, plasmapheresis
Biopsy findings in IgA
Immune complex deposition with mesangial IgA deposits
What are the two types of ANCA and what do they stain against?
cANCA = cytoplasmic staining, typically against proteinase 3 (PR3) pANCA = peri nuclear staining, typically against myeloperoxidase (MPO)
What are clinical features of granulomatosis with polyangitis?
Fever, polyarthralgia
Sinusitis, rhinorrhoea, nasal ulcers, saddle nose deformity due to polychondritis
Cough, haemoptysis, SOB
Microscopic haematuria, proteinuria, RPGN
Pupura
Mono neuritis multiplex
What small vessel vasculitis is associated with c-anca
Granulomatosis with polyangiitis
What small vessel vasculitis is associated with p-anca
Microscopic polyangiitis
Churg-Strauss is also associated with p-anca
What are the 2 classifications of membranoproliferative GN
1) Immune complex deposition
- caused by chronic infections, monoclonal gammopathy, autoimmune diseases
2) complement mediated
- caused by either dense deposit disease or c3 glomerulopathy
What is the pathogenesis of dense deposit disease
C3 nephritic factors which are anti-bodies which stabilise C3 convertase leading to continuous MAC complex formation
What is cryoglobulinaemia
Immunoglobulins that precipitate in the cold causing deposition of antigen-antibody complexes in small arterioles
What are the 3 types of cryoglobulinaemia
Type 1
Monoclonal IgM or IgG often due to multiple myeloma or waldenstroms
Type 2
Polyclonal IgG and monoclonal IgM RF against IgG
Often due to Hep b or c and EBV
Type 3
Polyclonal IgG and IgM RF
Due to SLE, sjogrens, lymphoproliferative malignancies and hep c
What are some clinical features of cryglobulinaemia
Palpable purpura, renal disease (usually MPGN), arthralgias, peripheral neuropathy, low complement
What are some causes of minimal change
Most common primary
Secondary: NSAIDs, allergies, Hodgkin’s disease
What are the biopsy findings in minimal change?
No findings on light microscopy or IF
EM shows effacement of podocyte foot processes
Clinical features of minimal change
Abrupt onset severe odema (average protein excretion greater then 10g/24hours) Hypoalbuminaemia Hypertension Microscopic haematuria Lipiduria
Treatment of minimal change
Steroids
- if adults are resistant to steroids consider doing a biopsy to look for FSGS
Other options: cyclophosphamide, mycophenolate
Adults respond less well to treatment, freq relapses
Epidemiology of FSGS
Ages 20-40
More common in African Americans
1/3 of nephrotic syndrome in adults
Causes of FSGS
Primary
Secondary - HIV, hep b, parvovirus, HTN, reflux nephropathy, cholesterol emboli, analgesics, pamidronate, alports, sickle cell, lymphoma
Pathology of FSGS
Segmental areas of mesangial collapse and sclerosis
Negative IF
Effacement of foot processes on EM
Clinical presentation of FSGS
Primary presents with nephrotic syndrome
Secondary presents less floridly - non nephrotic proteinuria, renal insufficiency
Treatment of FSGS
ACE-I
Treat underlying cause
Can trial steroids in primary
- recurs in grafts after transplant in 25-40%
Epidemiology of membranous nephropathy
30% of nephrotic syndrome in adults
More common in males (2:1)
Peak incidence 30-50
Idiopathic MN more common in white males over 59
MN in young females should raise suspicion for SLE
Causes of membranouse nephropathy
70% idiopathic
Secondary
- malignancy (breast, lung, colon,prostate)
- infection (Hep b, malaria, schistomasis)
- rheumatologic (SLE)
Pathology of membranous nephropathy
LM - thickening of basement membrane
IF - granular deposits of IgG and C3
EM - sub epithelial deposits, spikes ( expansion of GBM between sub epithelial deposits)
Progression of membranous nephropathy
1/3 spontaneously improve
1/3 remain stable
1/3 progress to ESRF
Treatment of membranous nephropathy
Immunosuppression in primary (steroids plus cyclophosphamide or Cyclosporin)
Ace-I if persistent proteinuria
- membranous has the highest rate of renal vein thrombosis, PE, DVT of all nephrotic syndrome
What are the four stages of diabetic nephropathy?
1 - hyperfiltration (first 5 years) 2 - microalbuminuric (30-300mg/24h) 3 - overt proteinuria (>300mg/24h) 4 - nephrotic syndrome, decreasing GFR 5 - ESRF ( 20-30 years)
Pathology of diabetic nephropathy
Thickening of BM
Negatively charged filtration barrier allows filtration of negatively charged albumin
Expansion of mesangium
Mesangial sclerosis
Hypertensive and hyaline arteriosclerosis
What are 3 types of glomerular deposition diseases
Light chain deposition disease (myeloma)
Renal amyloidosis
Fibrillary immunotactoid glomerulopathy
What is alports syndrome
X-linked mutation of alpha-5 chain of collagen type 4
Presentation with deafness, mild proteinuria, haematuria, lenticonus
What is thin basement membrane disease
Persistent recurrent haematuria without proteinuria/HTN/renal impairment or systemic disease
Benign
Often familial
What are the thrombotic microangiopathies?
TTP
- reduced ADAMTS13 activity resulting in ultra-large Von willibrand multimers that promote thrombosis
HUS
- caused by enteropathogens that release shiga toxins, which bind causing activation of platelets and thrombosis
