glomerulonephritis Flashcards
definition of glomerulonephritis
immunologically mediated inflammation of renal glomeruli.
what does glomerulonephritis encompass
are caused by pathology in the glomerulus
present with proteinuria, haematuria, or both
are diagnosed on a renal biopsy
cause CKD
can progress to kidney failure - except minimal change disease
spectrum of glomerulonephritis
glomerulonephritides present on a spectrum from nephrosis (proteinuria due to podocyte pathology) to nephritis (haematuria due to inflamm damage)
if glomerulonephritis causes scarring, proteinuria can happen - therefore proteinuria can complete the longer term clinical picture of any glomerulonephritis - even those that are classically nephritic
aetiology of glomerulonephritis
deposition of antigen–antibody immune complexes in the glomeruli that lead to inflammation and activation of complement and coagulation cascades.
immune complexes either form within glomerulus or are deposited in there by circ
ag unknown - occaisionally associated with:
infection
bacterial - Streptococcus viridans, group Ab-haemolytic streptococci, staphylococci, gonococci, Salmonella, syphilis.
viral - Hepatitis B/C, HIV, measles, mumps, EBV, VZV, coxsackie.
protazoal - plasmodium malariae, schistosomiasis, filariasis
inflammatory/systemic disease
- SLE
- systemic vasculitis
- cyroglobinaemia (Hepatitis B/C, HIV, measles, mumps, EBV, VZV, coxsackie.)
drugs - gold, penicillamine
tumours - Classified based on the site of nephron pathology and its distribution.
post-streptococcal glomerulonephritis
after a throat (2wk) or skin (3-6wk) infection
Streptococcal antigen deposits in the glomerulus leading to immune complex formation and infl ammation
minimal change glomerulonephritis
25% of adult nephrotic syndrome
idiopathic/drugs - NSAIDS, Lithium
paraneoplastic - haematological malignancy - usually hodgkin’s lymphoma
doesnt cause renal failure
normal appearance on light microscopy
electron microscopy = loss of epi foot processes
membranous glomerulonephritis
25% of adult nephrotic syndrome
Thickening of GBM from immune complex deposition. Associated with Goodpasture’s syndrome
primary - idiopathic
secondary
- malignancy - lung, breast, GI, prostate, haematological
- infection - hep B/C, strep, malaria, schistosomiasis
- immunological disease - SLE, RA, sarcoidosis, Sjogren’s
- drugs - gold, penicillamine
membraneoproliferative glomerulonephritis (MPGN)
10% of adult nephrotic syndrome (higher in low- and middle-income countries due to infection).
thickening of GBM, mesangial cell proliferation and interposition
Type 1: Subendothelial immune complex deposits and reduplication of GBM.
- immune complexes deposit in skin and activate complement
- underlying cause - infection, cryoglobulinaemia, monoclonal gammopathy, autoimmunity
Type 2: Dense intramembranous deposits (stain only for C3).
- genetic or acquired defect in alternative complement pathway eg C3 nephritic factor
- progressive kidney dysfunction is uncommon
focal segmental glomerulonephrosis
commonest GN seen on biopsy
primary - idiopathic
secondary - HIV, heroin, lithium, lymphoma, any cause of reduced kidney mass/nephrons, kidney scarring
all pts at risk of CKD and kidney failure
focal segmental proliferative glomerulonephritis
Mesangial and endothelial cell proliferation.
Focal refers to involvement of some of the glomeruli,
segmental refers to involvement of parts of individual glomeruli.
Diffuse proliferative glomerulonephritis
Mesangial and endothelial cell proliferation.
affects all glomeruli.
IgA nephropathy
Mesangial cell proliferation and mesangial IgA and C3 deposits.
Henoch–Schönlein purpura (HSP)
small vessel vasculitis and systemic variant of IgA nephropathy with IgA deposition in skin/joints/gut in addition to kidney
Crescentric glomerulonephritis:
Crescent formation by macrophages and epithelial cells,
which fills up Bowman’s space.
Focal segmental necrotizing glomerulonephritis:
Peripheral capillary loop necrosis (e.g. inWegener’s granulomatosis, microscopic polyarteritis and other vasculitides).
Often evolves into crescentric glomerulonephritis.
anti-glomerular basement membrane disease
previously known as goodpasture’s disease
rare
auto-ab to type IV collagen in glomerular and alveolar BM
rapidly progressive glomerulonephritis
any aggressive GN - rapidly progressing to renal failure over days or weeks
Causes include small vessel/ANCA vasculitis, lupus nephritis, anti-GBM disease. Other GNs may ‘transform’ to become rapidly progressive including IgA, membranous.
epidemiology of glomerulonephritis
Makes up to 25% of cases of chronic renal failure.
IgA nephropathy - commonest primary GN in high-income countries
sx of glomerulonephritis
haematuria
subcutaneous oedema
polyuria or oliguria
proteinuria
history of recurrent infection
Symptoms of uraemia or renal failure (acute and chronic).
sx of IgA nephropathy
asymptomatic
non-visible haematuria
episodic visible haematuria - may be ‘synpharyngitic’: within 12–72h of infection
high BP
proteinuria <1g
slow, indolent disease - 20-50% progress to renal failure over 30yrs
sx of HSP
purpuric rash on extensor surfaces - typically on legs
flitting polyarthritis
abdo pain - GI bleeding
nephritis
sx of post-streptococcal glomerulonephritis
varies from haematuria to acute nephritis (haematuria, oedema, HTN, oliguria)
sx of anti-glomerular basement membrane disease
renal disease - oliguria/anuria, haematuria, AKI, renal failure
lung disease - pul haemorrhage in 50-90% = SOB, haemoptysis
sx of glomerulonephritis
HTN
proteinuria <3g/24hr
haematuria (microscopic or macroscopic, especially IgA nephropathy);
nephrotic syndrome
nephritic syndrome - haematuria, proteinuria, subcutaneous oedema, oliguria, hypertension, uraemia);
renal failure - acute/chronic
partial lipodystrophy (loss of subcutaneous fat in MPGN type II).
Ix for glomerulonephritis
blood
urine
imaging - renal tract US and CXR
renal biopsy
hep B, C, HIV serology
bloods for glomerulonephritis
FBC
UE
CRP
creatinine
LFT - albumin
lipid profile
electrophoresis
complement studies -C3, C4, C3 nephritic factor in MPGN
ANA
anti-double stranded DNA
ANCA
anti-GBM Ab
cyroglobins if appropriate
culture
urine for glomerulonephritis
microscopy - dysmorphic RBC, red cell casts
24hr collection - creatinine clearance, protein
MC&S,
Bence Jones protein
imaging for glomerulonephritis
renal tract US - exclude other path. Size and anatomy for biopsy
CXR - pul haemorrhage
renal biopsy for glomerulonephritis
light microscopy, electron light microscopy, immunofluorescence microscopy
needed for diagnosis
Ix for IgA nephropathy
biopsy - IgA deposition in mesangium
Ix for HSP
diagnosis clinical
positive IF for IgA and C3 in skin
renal biospy same as IgA nephropathy
Ix for post-strep glomerulonephritis
evidence of strep infection
- high ASOT
- high anti-DNAse B
- low C3
Ix for anti-GBM glomerulonephritis
anti-GBM in circ/kidney
Ix for rapidly progressive glomerulonephritis
breaks in GBM allow influx of inflamm cells so that cresents are seen on renal biopsy - may be referred to as cresentic GN
Ix for minimal change disease
light microscopy normal
electron microscopy - effacement of podocyte foot processes
Ix for FSGS
glomeruli have scarring of certain segments (ie focal sclerosis)
may miss early disease if <10 glomeruli in biopsy sample
Ix for membranous nephropathy
Anti-phospholipase A2 receptor antibody in 70–80% of idiopathic disease.
Diffusely thickened GBM due to subepithelial deposits (IgG4 dominant in idi-opathic, other IgGs in secondary disease).
‘Spikes’ on silver stain
Ix for membranoproliferative glomerulonephritis
a proliferative glomerulonephritis with electron dense deposits
immunoglobin deposition distinguishes immune-complex-associated disease from C3 glomerulopathy
