Glomerulonephritis Flashcards
What is glomerulonephritis
is a renal disease
characterised by inflammation and damage to the
glomeruli.
The ‘glomerulopathies’ are a constellation of diseases
characterised by injury to renal glomeruli.
This glomerular damage allows protein (with or
without blood) to leak into the urine (proteinuria
and haematuria respectively).
What layers make up the filtration barrier
Endothelium - capillary wall
Basement membrane - selective barrier to macromolecules
Foot processes podocytes (specialised epithelial cells)
Secondary causes glomerulonephritis
Vasculitis (ANCA-ass vasculitis)
Amyloidosis
Diabetes mellitus
Primary causes of glomerulonephritis
IgA nephropathy
Minimal change disease
Focal segmental glomerulosclerosis
Focal vs diffuse glomerulopathy
50% cut off - number of glomeruli affected
Global vs segmental glomerulopathy
50% of glomerulus itself is cut off
Immune mediated glomerulus damage
Immune complex deposition
activate pro inflam and complement response
Circulating anitbodies target key basement membrane proteins or endothelial cells -> inflammatory reaction
Non immune damage to glomeruli mechanism
Structure and/or function of podocytes affected disrupt filtration barrier -> larger macromolecules leak through
OR
accumulation of non immune material -> dysgunction
Histological patterns
Proliferative - increased cells + inflam response
Non proliferative - structural - sclerosis
Crescents - extracapillary lesions in bowmans capsule due to immune cell accumulartion = severe injury to capillary wall
What glomerulonephrotic diseases are proliferative
Glomerular inflammation with haematuria +/- nephritic syndrome
what glomerulopathies are non proliferative
Excess protein loss and nephrotic syndrome
Groups of glomerulopathies
Isolated haematuria
Isolated proteinuria
Nephrotic syndrome
Nephritic syndrome
Rapidly progressive glomerulonephritis
What is a crescent
extracapillary lesions in Bowan’s capsule
due to accumulation of immune cells, fibroblasts,
epithelial cels and fibrin. Crescents represent
severe injury to the capillary wall that results in
glomerular membrane rupture.
What is isolated haematuria
Persistent haematuria in absence of proteinuria and normal renal function
Reassess over 1-4 weeks to determine
Causes of isolated haematuria
IgA nephropathy
Alport syndrome
Thin basement membrane disease
Exclude non renal causes
What causes isolated proteinuria
Glomerular
Tubular
Overflow
Post renal
What is isolated proteinuria
Persistent proteinuria in absence of other urinary abnormality and normal renal functioon
Non nephrotic in range <3.5 g/day
Benigin causes of proteinuria
Transietn - young patients - absent on repeat testing and exercise precipitates
Orthostatic proteinuria - presence only in upright position
Renal screen
Complement
ANA
ANCA
GBM
Anti-dsDNA
Myeloma screen - serum free light chains, protein electrophoresis
Anti-PLA2R AA
Virology - Hep B, C + HIV
Cryoglobulins
CK
What is anti-PLA2R autoantibody raised in
Membranous nephropathy
What is complement typically low in
Vasculitis
Myeloma screen
serum free lights chains, protein
electrophoresis
What is anti-dsDNA riased in
SLE
CT KUB use in glomerulonephritis
Rule out obstructive pathology
Assess structure of kidneys
Managmenet principles for all glomerular conditions
Regular monitoring
Treat underlying cuase
Determine natural history eg supportive or involved treat needed
Treat complications
Consider RRT
What disease can be both nephritic and nephrotic
Membranous proliferative GN
What mostly causes nephrotic syndrome in young children?
Minimal change disease (90% cases under 10)
Causes of minimal change disease
majority are idiopathic
drugs - NSAIDs
Malignancy - lymphoproliferative disorders
Infections eg syphilis
What is seen on electromicroscopy in minimal change disease
Fusion of podocyte foot processes
What is pulmonary renal syndrome
Diffuse alveolar haemorrhage + glomerulonephritis caused by an AI disorder - serologic tests and lung/renal biopsy
Treatment of pulmonary renal syndorme
Immunosupress - corticosteroids, cytotoxic drugs
Groups of causes of glomerular disease
Nephrotic
Nephritis
Chronic renal failure
Rapidly progressive GN
Asymptomatic haematuria/proteinura
What causes asymtpomatiic haemturia/proteinura
alport syndreom - hereditary nephritis
What is RPGN
Immune complex mediated crescenteric GN
Causes of RPGN
Pauci immune - ANCA +
Anti- GBM (goodpasteurs)
Antibody mediated crescenteric GN
What systemic diseases can cause nephritic syndrome
Diabetic nephropathy
Amyloidosis
#SLE
Causes of nephrotic syndrome
Systemic
FSGS
Membranous glomerulopathy
Minimal change disease
MPGN
Causes of nephritic syndrome
Acute post infectious GN
IgA nephropathy - Bergers
CTDs causing glomerulonephritis
Dermatomysositis
Polymyositis
Progressive systemic sclerosis
RA
SLE
Systemic vasculitis causing GN
Cryoglobuniamia
GPA (weheners0
Microscopic polyangitis
Eosinophilic granulomatosis w polyangitis
IgA ass vasculitis
What drug can cause GN
Propylthuouracil (for hyperthyroidis)
Crescenteric GN on histology
Darker purple area on R side of lomerulus
Cardinal feature of GN
Haematuria + red cell casts in urine
Aetiological factors for GN
bacteria:
Staphylococcus spp.
Lancefiled group A B-haemolytic streptococci
Streptococcus viridans
Treponema pallidum
viruses:
Coxsackie virus
Epstein Barr virus
hepatitis B virus
measles
mumps
parasites:
Plasmodium malariae
Schistosoma spp.
drugs:
penicillamine
host antigens:
cryoglobulin
DNA
tumour antigens
What disease does complement mediated glomerular damage occur in
Proliferative GNs
How long after infection does post strep GN occur
7-14 dyas after group A beta haemolytic strep - usually strep pyogene. Often URTI
What causes post strep GN
Immune complex - IgG, IgM, C3 dpeosition in glomeruli. Most common in young childrne
Features of post strep GN
general
headache
malaise
visible haematuria
proteinuria
this may result in oedema
hypertension
oliguria
Bloods in post strep GN
Raised anti streptolysin O titre - confirm recent strep infetion
Low C 3
Features of post strepGN on biopsy
acute, diffuse proliferative glomerulonephritis
endothelial proliferation with neutrophils
electron microscopy: subepithelial ‘humps’ caused by lumpy immune complex deposits
immunofluorescence: granular or ‘starry sky’ appearance
What are anti-GBM antibodies
Atibodies against Type IV cl=ollagen
What gene is anti-GBM ass with
HLA-DR2
What is goodpasteurs and who common in
Rare small-vessel vasculitis associated with both pulmonary haemorrhage and rapidly progressive glomerulonephritis
Men 2;1, bimodal age- 20-30 and 60-70.
Features of goodpasteurs syndrome
pulmonary haemorrhage
rapidly progressive glomerulonephritis
this typically results in a rapid onset acute kidney injury
nephritis → proteinuria + haematuria
Investigations for glomeruloneprhtitis
Renal biopsy - linear IgG deposite basement membrane
Raised transfer factor - pulm haemorrahge
Management of goodpasteurs
Plasma exchagne #Steroids
Cyclophosphamide
How does membranous GN present
Nephrotic syndrome + proeinuria
Rena biopsy in membranous GN
electron microscopy: the basement membrane is thickened with subepithelial electron dense deposits. ‘spike and dome’ appearance
Causes of mebranous GN
Idiopathic 0 anti-phospholipase A2 antibodies
Infection - hep B, malaria, syphilis
Malignancy - prosteate, kung, lymohoma, leukaemia
Drugs - gold, penicillamine, NSAIds
AI - SLE (class V) , thryoiditis, rheumatoid
Managemnet of membranous GN
ACEi or ARB - reduce proteinuria
Immunosupression = only if severe or progressive
Corticosteroids + cyclophosphamide
Anticoag if high risk
Prognsosis of membranous GN
1/3 - spontaneous remission
1/3 - reamin proeinuric
1/3 - end stage renal failure
Female, young and asymptomatic modest proteinuria are good prongoses
Causes of focal segmental glomuerulosclerosis
Idiopathic
Renal pathology eg IgA or reflux nephropathy
HIV
heroin
Alports syndrome
Sickle cell
High recurrence in renal transplants
Renal biopsy of FSGS
focal and segmental sclerosis and hyalinosis on light microscopy
effacement of foot processes on electron microscopy
Treatmet and prognosis FSGS
Steroids + immunosupressants if needed
Untreated <10% chance remission
