Glomerulonephritis Flashcards
Rapidly progressive glomerulonephritis: rapid loss of renal function associated with formation of ___ ___ in the majority of glomeruli.
epithelial crescents
causes of rapidly progressive glomerulonephritis?
Anti-GBM disease (Goodpastures)
GPA (Wegener’s)
SLE, microscopic polyarteritis
features of rapidly progressive glomerulonephritis?
nephritic syndrome: haematuria with red cell casts, proteinuria, hypertension, oliguria
features specific to underlying cause: haemoptysis in anti-GBM, vasculitis rash or sinusitis with Wegener’s
what is anti-glomerular basement membrane (GBM) disease?
previously known as Goodpasture’s syndrome
rare type of small-vessel vasculitis associated with both both pulmonary haemorrhage and rapidly progressive glomerulonephritis
anti-glomerular basement membrane (GBM) disease
1) cause
2) associated with what gene mutation
3) features?
1) anti-GBM antibodies against type IV collagen
2) HLA-DR2
3) pulmonary haemorrhage, rapidly progressIive GM: rapid onset AKI, nephritis (proteinuria + haematuria)
anti-glomerular basement membrane (GBM) disease
1) investigations?
2) management?
1) renal biopsy (linear IgG deposits along BM), raised transfer factor due to pulmonary haemorrhage
2) plasmapheresis, steroids, cyclophosphamide
what is the main complication of anti-glomerular basement membrane? what factors increase risk of this occurring?
pulmonary haemorrhage
- smoking, LRTI, pulmonary oedema, inhalation of hydrocarbons, young male
What is granulomatosis with polyangiitis (prev Wegener’s)
an autoimmune condition associated with necrotising granulomatous vasculitis, affecting both upper and lower respiratory tract + kidneys
features of granulomatosis with polyangiitis?
upper RT: epistaxis, nasal crusting
lower RT: haemoptysis, dyspnoea
rapidly progressive GM
Saddle shaped nose deformity
Ix in GPA?
cANCA +ve >90% (pANCA in 25%)
CXR: cavitating lesions
Renal biopsy: epithelial crescents in Bowman’s capsule
Management of GPA?
Steroids
Cyclophosphamide (90% response)
Plasma exchange
NB: median survival is 8-9 years
Membranoproliferative glomerulonephritis is aka ______ glomerulonephritis. It may present how? Prognosis?
mesangiocapillary
nephrotic syndrome, proteinuria, haematuria
poor prognosis
Membranoproliferative glomerulonephritis
1) type 1 or 2 more common?
2) cause of type 1?
3) renal biopsy of type 1?
1) type 1 (90%)
2) cryoglobulinaemia, hepatitis C
3) ‘tram-track appearance’
Membranoproliferative glomerulonephritis type 2
1) cause
2) patients wwill have low circulating levels of ___
3) ___ ___ factor is found in 70%
4) renal biopsy
1) partial lipodystrophy (classically loss of sc tissue in their face), factor H deficiency. Caused by persistent activation of complement pathway.
2) C3
3) C3b nephritic factor
4) ‘dense deposits’
tetrad of nephrotic syndrome?
proteinuria (>3g/ day)
hypoalbuminaemia (<30g/L)
hypercholesterolaemia
Oedema
what type of glomerulonephritis is
1) nephritic
2) nephrotic
syndrome associated with
1) rapidly progressive (anti-GBM, GPA), IgA nephropathy
2) membranous, focal segmental
causes of nephrotic syndrome?
membraneous GN minimal change disease focal segmental glomerulosclerosis amyloidosis diabetic nephropathy
why is there increased risk of thrombosis in nephrotic syndrome?
loss of anti-thrombin III, protein C and S plus associated rise in fibrinogen levels
why is there increased risk of thrombosis in nephrotic syndrome?
loss of anti-thrombin III, protein C and S plus associated rise in fibrinogen levels
commonest cause of gloumerulonephritis?
IgA nephropathy (Berger’s disease)
IgA nephropathy classic presentation?
macroscopic haematuria in young people following an URTI
conditions associated with IgA nephropathy?
alcoholic cirrhosis
coeliac/ dermatitis herpetiformis
Henoch schonlein purpura
IgA nephropathy
1) pathophysiology
2) histology
1) mesangial deposition of IgA immune complexes
2) mesangial hypercellularity, positive immunofluroscence for IgA and C3
IgA nephropathy
Typically presents in a young ___ with recurrent episodes of ___ ___
Typically associated with a recent ____
Nephrotic range proteinuria is COMMON/ RARE
Renal failure is COMMON/ RARE
males macroscopic haematuria (IgA - mAcroscopic)
URTI
rare
rare
Differentiating between IgA nephropathy and post-streptococcal glomerulonephritis
post-strep GN is associated with low ____ levels
main symptom in post-strep GN is ______
Interval from URTI to onset of renal problems is approximately __ __ in IgA nephropathy and __ __ in post-strep GN
complement
proteinuria (although haematuria can occur)
1-2d IgA
1-2w PSGN
T/F: steroids/ immunosuppression is first line in IgA nephropathy
false - not shown to be useful
IgA nephropathy
1) markers of good prognosis?
2) markers of poor prognosis?
1) frank haematuria
2) male, proteinuria (esp>2g/ day), smoking, hypertension, hyperlipidaemia, ACE genotype DD
25% develop ESRF
membranous glomerulonephritis is the common type of GN in ___. It usually presents with ___ syndrome or ___
adults
nephrotic
proteinuria
what is seen on electron microscopy of a renal biopsy in membranous GN?
thickened BM with subepithelial electron dense deposits
> ‘spike and dome’ appearance
Management of membranous GN?
all patients given ACEI or ARB (reduces proteinuria and improves prognosis)
immunosuppression only if symptoms severe/ progressive (many improve spontaneously)
prognosis rule of thirds in membranous GN?
1/3 spontaneous remission
1/3 remain proteinuric
1/3 develop ESRF
T/F: if indicated, corticosteroids are the agent of choice in membranous GN
false- corticosteroids alone not useful
use corticosteroid + something else e.g. cyclophosphamide
Causes of membranous GN
idiopathic: due to ____ ____ antibodies
infections e.g. …
malignancy (in 5-20%): prostate, lung, lymphoma, leukaemia
drugs e.g. …
autoimmune disease e.g. …
anti-phospholipase A2
hepatitis B, malaria, syphilis
gold, penicillamine, NSAIDs
systemic lupus erythematosus (class V disease), thyroiditis, rheumatoid
in nephrotic syndrome, inflammation of the ___, causes damage to which cells?
what is the function of these cells?
glomerulus
podocytes- which normally function to prevent protein loss
T/F: haematuria is not seen in nephrotic syndrome
false- may be seen, depending on degree of damage to glomerulus
why are those with nephrotic syndrome at increased risk of infection?
loss of immunoglobulins (which are proteins)
why does hypercholesterolaemia occur in nephrotic syndrome?
loss of protein > liver works overtime to replace > increased production of albumin and cholesterol
why is GFR decreased in nephrotic syndrome?
water moves out of circulating volume to interstitium > decreased venous return to heart > decreased renal blood flow
signs and symptoms in nephrotic syndrome?
hypercholesterolaemia> xanthelasma, xanthomata
hypoalbuminaemia > tired, leukonychia, oedema (periorbital, ascites, peripheral, pulmonary)
proteinuria > frothy urine
Focal segmental glomerulosclerosis (FSGS) is a cause of _____ syndrome and chronic kidney disease.
It generally presents in what age group?
T/F: renal transplant is generally curative
Renal biopsy
- on light miscoscopy?
- on electron microscopy?
management?
nephrotic
young adults
false- high rate of recurrence in renal transplants
light: focal and segmental sclerosis and hyalinosis
electron: effacement of foot processes
steroids +/- immunosuppressants
Alport’s syndrome is usually inherited in what pattern?
It is due to a defect in the gene which codes for type IV ___ resulting in an abnormal ___ ___ ___
The disease is more severe in MALES/ FEMALES
x-linked dominant
collagen
glomerular BM
males
presentation of Alport’s syndrome?
microscopic haematuria
progressive RF
bilateral SN deafness
lenticonus
retinitis pigmentosa
electron micoscopy of renal biopsy in Alport’s syndrome?
splitting of lamina densa (‘basket weave’ appearance)
Post-streptococcal glomerulonephritis typically occurs ___ ___ following what?
It is caused by ___ ___ deposition in the glomeruli.
Young children are most commonly affected.
1-2 weeks
a group A beta-haemolytic Streptococcus infection (usually S.pyogenes)
immune complex (IgG, IgM and C3)
what type of GN produces a ‘starry sky’ appearance on immunofluorescence?
post-strep GN
Nephrotic syndrome
1) classic triad
2) other features: hyper____, a hyper___ state (due to loss of __ __) and a predisposition to ____ (due to loss of ____)
3) there is also an assocation with HYPER/ HYPO calcaemia- why?
1) proteinuria, hypoalbuminaemia, oedema
2) hyperlipidaemia, hypercoagulable state (loss of antithrombin III), predisposition to infection (loss of IGs)
3) hypocalcaemia (vit D lost in urine)
what is seen on urinalysis in nephritic syndrome?
red cell casts
minimal change disease nearly always presents as ___ syndrome
T/F: most causes are idiopathic
Potential causes?
nephrotic
true
10-20% of cases have causes: drugs (NSAIDS, rifampicin), Hodgkin’s lymphoma, thymoma
Infectious mono
features of minimal change disease?
nephrotic syndrome
normotension
highly selective proteinuria (intermediate sized proteins e.g. albumin and transferrin leak through)
what is seen on renal biopsy in minimal change disease?
light: glomerulus normal (hence ‘MINIMAL CHANGE’)
electron: fusion of podocytes, effacement of foot processes
minimal change disease management?
80% corticosteroid responsive
cyclophosphamide 2nd line
most common nephrotic syndrome in children?
minimal change disease
this is the pathophysiology of which cause of nephrotic syndrome
‘T-cells release cytokines that damage foot processes of podocytes. Leads to selective proteinuria’
minimal change disease
