Glomerulonephritis Flashcards
What are the features of nephritic syndrome?
Haematuria - This can be microscopic (not visible) or macroscopic (visible).
Oliguria - significantly reduced urine output.
Proteinuria is protein in the urine. In nephritic syndrome, there is less than 3g / 24 hours. Any more and it starts being classified as nephrotic syndrome.
Fluid retention
Hyaline casts in urine are pathonogmonic of?
consist of Tamm-Horsfall protein (secreted by distal convoluted tubule)
seen in normal urine, after exercise, during fever or with loop diuretics
brown granular casts in urine are pathonogmonic of?
Acute tubular necrosis
‘bland’ urinary sediment in urine are pathonogmonic of?
Prerenal uraemia
Red cell casts in urine are pathonogmonic of?
nephritic syndrome
What is the triad of nephrotic syndrome?
- Proteinuria (> 3g/24hr) causing
- Hypoalbuminaemia (< 30g/L) and
- Oedema
Why do you get an increased risk of thromboembolism in nephrotic syndrome?
Loss of antithrombin-III, proteins C and S and an associated rise in fibrinogen levels predispose to thrombosis.
Nephrotic syndrome results in a loss of total thyroxine levels
true
Loss of thyroxine-binding globulin lowers the total, but not free, thyroxine levels.
List conditions associated with nephritic syndrome
Rapidly progressive GN
IgA nephropathy
Alport Syndrome
List conditions associated with nephrotic syndrome
Minimal change disease Membranous GN Focal segmental glomerulosclerosis Amyloidosis Diabetic Nephropathy
List conditions associated with both nephritic and nephrotic syndromes
Diffuse proliferative GN
Membranoproliferative GN
Post-strep GN
List complications of nephrotic syndrome
increased risk of thromboembolism related to loss of antithrombin III and plasminogen in the urine- deep vein thrombosis, pulmonary embolism
renal vein thrombosis, resulting in a sudden deterioration in renal function
hyperlipidaemia
increasing risk of acute coronary syndrome, stroke etc
chronic kidney disease
increased risk of infection due to urinary immunoglobulin loss
hypocalcaemia (vitamin D and binding protein lost in urine)
Peak incidence of nephrotic syndrome in children?
between 2 and 5 years of age
Around 80% of cases of nephrotic syndrome in children are due to
minimal change glomerulonephritis
minimal change glomerulonephritis. generally carries a good prognosis
true
What % of cases respond to high-dose oral steroids in minimal change gn
90%
Rapidly progressive glomerulonephritis is a term used to describe
rapid loss of renal function associated with the formation of epithelial crescents in the majority of glomeruli.
Causes of Rapidly progressive glomerulonephritis?
Goodpasture’s syndrome
Wegener’s granulomatosis
others: SLE, microscopic polyarteritis
Features of Rapidly progressive glomerulonephritis?
nephritic syndrome: haematuria with red cell casts, proteinuria, oliguria
hypertension
features specific to underlying cause e.g.
haemoptysis with Goodpasture’s
vasculitic rash or sinusitis with Wegener’s
Commonest cause of GN worldwide?
IgA nephropathy
IgA nephropathy is also known as Berger’s disease
yes
IgA nephropathy classically presents as micro or macroscopic haemturia?
MACRO
How does IGA nephropathy classically present?
macroscopic haematuria in young male following an upper respiratory tract infection.
Associated condition with IGa nephropathy?
alcoholic cirrhosis
coeliac disease/dermatitis herpetiformis
Henoch-Schonlein purpura
Describe pathophysiology of iga nephropathy
thought to be caused by mesangial deposition of IgA immune complexes
there is considerable pathological overlap with Henoch-Schonlein purpura (HSP)
histology: mesangial hypercellularity, positive immunofluorescence for IgA & C3
Iga Nephropathy never presents with nephrotic range proteinuria
nephrotic range proteinuria is rare
Renal failure is common in iga nephropathy
renal failure is unusual and seen in a minority of patients
How would ou differentiate between IgA nephropathy and post-streptococcal glomerulonephritis?
post-streptococcal glomerulonephritis is associated with low complement levels
main symptom in post-streptococcal glomerulonephritis is proteinuria (although haematuria can occur)
there is typically an interval between URTI and the onset of renal problems in post-streptococcal glomerulonephritis
Mainstay of management for Iga nephropathy is steroids/immunosuppressants
false
steroids/immunosuppressants not be shown to be useful
Describe markers of good prognosis in Iga nephropathy
frank haematuria
Describe markers of poor prognosis in Iga nephropathy
male gender proteinuria (especially > 2 g/day) hypertension smoking hyperlipidaemia ACE genotype DD
% of patients develop ESRF in Iga nephropathy
25%
What do Iga nephropathy and post streptococcal glomerulonephritis have in common
recent urti
haematuria
How is Alport’s syndrome inherited?
X-linked dominant pattern
what is alports syndrome due to
defect in the gene which codes for type IV collagen resulting in an abnormal glomerular-basement membrane (GBM)
Alports is more severe in which sex
males
Alports rarely results in renal failure
true
What is a favourite exam Q according to passmed
A favourite question is an Alport’s patient with a failing renal transplant. This may be caused by the presence of anti-GBM antibodies leading to a Goodpasture’s syndrome like picture.
Alport’s syndrome usually presents in childhood.
YEA
Describe features of alports?
microscopic haematuria progressive renal failure bilateral sensorineural deafness lenticonus: protrusion of the lens surface into the anterior chamber retinitis pigmentosa
Renal biopsy in alports
characteristic finding is of the longitudinal splitting of the lamina densa of the glomerular basement membrane, resulting in a ‘basket-weave’ appearance
on electron microscopy
Diagnosis of Alports
molecular genetic testing renal biopsy (electron biopsy)
buzzword for alports
‘basket-weave’ appearance
Alports can never beinherited in autosomal domiannt fashion
false
10-15% of cases are inherited in an autosomal recessive fashion with rare autosomal dominant variants existing
Minimal change disease nearly always presents as which syndrome
nephrotic
Minimal change disease nearly always presents as nephrotic syndrome, accounting for ?% of cases in children and ?% in adults.
75% of cases in children and 25% in adults.
Causes of minimal change?
The majority of cases are idiopathic
In around 10-20% a cause is found:
drugs: NSAIDs, rifampicin
Hodgkin’s lymphoma
thymoma
infectious mononucleosis
Pathophysiology of minimal change?
T-cell and cytokine-mediated damage to the glomerular basement membrane → polyanion loss
the resultant reduction of electrostatic charge → increased glomerular permeability to serum albumin
Minimal change presents with hypertension
false
normotension - hypertension is rare
Minimal change has a highly selective proteinuria - describe this
only intermediate-sized proteins such as albumin and transferrin leak through the glomerulus
How do diagnose minimal change?
Clinical test. Biopsy only indicated if steroid resistance
What is the test for minimal change? Findings?
biopsy electron microscopy shows fusion of podocytes and effacement of foot processes
normal glomeruli on light microscopy
Management of minimal change?
majority of cases (80%) are steroid-responsive
cyclophosphamide is the next step for steroid-resistant cases
Describe prognosis of minimal change?
1/3 have just one episode
1/3 have infrequent relapses
1/3 have frequent relapses which stop before adulthood
Commonest glomerulonephritis in adults?
Membranous glomerulonephritis
Membranous glomerulonephritis is the third most common cause of end-stage renal failure (ESRF).
true
How does Membranous glomerulonephritis usually present?
It usually presents with nephrotic syndrome or proteinuria.
Membranous glomerulonephritis - renal biopsy?
electron microscopy: the basement membrane is thickened with subepithelial electron dense deposits.
This creates a ‘spike and dome’ appearance
Causes of Membranous glomerulonephritis?
idiopathic: due to anti-phospholipase A2 antibodies
infections: hepatitis B, malaria, syphilis
malignancy (in 5-20%): prostate, lung, lymphoma, leukaemia
drugs: gold, penicillamine, NSAIDs
autoimmune diseases: systemic lupus erythematosus (class V disease), thyroiditis, rheumatoid
Management of membranous GN?
all patients should receive an ACE inhibitor or an angiotensin II receptor blocker (ARB)
immunosupression
as many patients spontaneously improve only patient with severe or progressive disease require immunosuppression
corticosteroids alone have not been shown to be effective. A combination of corticosteroid + another agent such as cyclophosphamide is often used
consider anticoagulation for high-risk patients
Why are ACEi / ARB used in membranous GN?
these have been shown to reduce proteinuria and improve prognosis
Prognosis of membranous GN?
one-third: spontaneous remission
one-third: remain proteinuric
one-third: develop ESRF
Good prognostic features for membranous GN?
female sex, young age at presentation and asymptomatic
proteinuria of a modest degree at the time of presentation.
Focal segmental glomerulosclerosis (FSGS) is a cause of
nephrotic syndrome and chronic kidney disease
FSGS generally presents in
young adults
Causes of FSGS?
idiopathic
secondary to other renal pathology e.g. IgA nephropathy, reflux nephropathy
Alport’s syndrome!
HIV
heroin
sickle-cell
Focal segmental glomerulosclerosis is noted for having a high recurrence rate in renal transplants.
true
Investigations in FSGS?
renal biopsy: focal and segmental sclerosis and hyalinosis on light microscopy
effacement of foot processes on electron microscopy
Management of FSGS?
steroids +/- immunosuppressants
Prognosis of FSGS?
untreated FSGS has a < 10% chance of spontaneous remission
amyloidosis is a term which describes
extracellular deposition of an insoluble fibrillar protein termed amyloid
the accumulation of amyloid fibrils leads to tissue/organ dysfunction
amyloid is derived from many different precursor proteins
true
in addition to the fibrillar component, amyloid also contains
non-fibrillary protein called amyloid-P component, derived from the acute phase protein serum amyloid P
other non-fibrillary components include apolipoprotein E and heparan sulphate proteoglycans
Classification of amyloidosis?
systemic or localized
further characterised by precursor protein (e.g. AL in myeloma - A for Amyloid, L for immunoglobulin Light chain fragments)
Diagnosis of amyloidosis?
Congo red staining: apple-green birefringence
serum amyloid precursor (SAP) scan
biopsy of rectal tissue
How often should diabetic patients be screened for renal problems? How is this done?
all patients should be screened annually
urinary albumin:creatinine ratio (ACR)
should be an early morning specimen
For diabetic nephropathy
ACR > ? = microalbuminuria
2.5
Management of diabetic nephropathy?
dietary protein restriction
tight glycaemic control
BP control
control dyslipidaemia e.g. Statins
Aim for BP control in diabetic nephropathy?
<130/80mmghg
in diabetic nephropathy benefits independent of blood pressure control have been demonstrated for ACE inhibitors (ACE-i) and angiotensin II receptor blockers (A2RB).
true
Combinations of ACE-i and A2RB are not commonly used anymore following the ON-TARGET trial which showed worse outcomes for patients on dual blockade in diabetic nephropathy
true
Membranoproliferative glomerulonephritis is also known as
mesangiocapillary glomerulonephritis
How does Membranoproliferative glomerulonephritis present?
nephrotic syndrome, haematuria or proteinuria
Prognosis of Membranoproliferative glomerulonephritis
poor
Which type of Membranoproliferative glomerulonephritis is most common?
Type 1
What is Type 1 Membranoproliferative glomerulonephritis caused by?
cryoglobulinaemia, hepatitis C
What is type 2 Membranoproliferative glomerulonephritis caused by?
causes: partial lipodystrophy (patients classically have a loss of subcutaneous tissue from their face)
factor H deficiency
caused by persistent activation of the alternative complement pathway
Type 1 Membranoproliferative glomerulonephritis will show what on renal biopsy?
electron microscopy: subendothelial and mesangium immune deposits of electron-dense material resulting in a ‘tram-track’ appearance
Type 2 Membranoproliferative glomerulonephritis will have low circulating levels of what? Why is this?
C3
C3b nephritic factor is found in 70%
an antibody to alternative-pathway C3 convertase (C3bBb)
stabilizes C3 convertase
What will Type 2 Membranoproliferative glomerulonephritis show on biopsy?
electron microscopy: intramembranous immune complex deposits with ‘dense deposits’
What is T3 Membranoproliferative glomerulonephritis caused by?
hepatitis B and C
How is Membranoproliferative glomerulonephritis managed?
steroids may be effective
Post-streptococcal glomerulonephritis typically occurs how long following a group A beta-haemolytic Streptococcus infection
7-14 days
What is the usual culprit for post strep GN?
Streptococcus pyogenes
Describe pathophysiology of post strep GN
immune complex (IgG, IgM and C3) deposition in the glomeruli
Who is most commonly affected by post strep GN
children
Signs & symptoms of post strep GN?
Headache, malaise
Visible haematuria, proteinuria which may result on edema, oliguria
Hypertension
What will bloods show in post strep GN?
low C3
raised ASO titre
Post strep GN has a good prognosis
yes
Renal biopsy features in Post strep GN
post-streptococcal glomerulonephritis causes acute, diffuse proliferative glomerulonephritis
endothelial proliferation with neutrophils
electron microscopy: subepithelial ‘humps’ caused by lumpy immune complex deposits
immunofluorescence: granular or ‘starry sky’ appearance
