What is glomerulonephritis?
Autoimmune disease of the glomeruli
What is the commonest cause of renal failure after diabetes?
Glomerulonephritis
What immune components mediate glomerulonephritis?
Antibodies
T cells
Inflammatory cells, cytokines, complement
What are the three layers of the glomerular membrane?
Endothelium of glomerular capillary
Glomerular basement membrane
Podocytes
Glomerulonephritis causes disruption of which structure?
What symptoms are seen?
Glomerular membrane
Proteinuria
Haematuria
What signs are produced if glomerulonephritis damages
a) endothelial or mesangial cells
b) podocytes?
a) Haematuria
b) Proteinuria
What happens to podocytes when they are damaged by glomerulonephritis?
Atrophy
No inflammation, but allows leakage of protein
What happens to mesangial cells if they are damaged by glomerulonephritis?
Proliferation
Vasoconstriction (by angiotensin II)
Inflammatory response
Haematuria
What happens to endothelial cells if they are damaged by glomerulonephritis?
Vasculitis
Haematuria
Endothelial damage causes (slow / rapid) decline in renal function.
rapid decline in renal function
Does mesangial damage cause rapid decline in renal function?
No
Haematuria and proteinuria
What urine tests can be done for someone with glomerulonephritis?
Urinalysis
Urine microscopy - for cell casts, culture
P/C ratio - to quantify proteinuria
What investigation can you do if you’re struggling to classify glomerulonephritis after urine analysis?
Kidney biopsy
Is haematuria painful?
No
may be in UTI
On urine microscopy, what do red blood cells look like if they’ve come from the
a) kidneys
b) bladder?
a) Dysmorphic
b) Intact
What type of casts are seen in glomerulonephritis?
Red cell casts
pathognomic of GN, usually endothelial damage
What can acutely or chronically deteriorate due to glomerulonephritis?
Renal function
What are the presentations of
a) NEPHRITIC SYNDROME
b) NEPHROTIC SYNDROME?
a) Acute renal failure, oliguria, oedema, hypertension, urinary sediment
caused by inflammation
b) Proteinuria, hypoalbuminaemia, oedema, hypercholesterolaemia
due to inability of kidneys to retain albumin
What type of glomerulonephritis causes nephritic syndrome?
Endothelial
Mesangial
because they proliferate and cause inflammation
What type of glomerulonephritis causes nephrotic syndrome?
Podocyte damage
What is renal function like in
a) nephrotic syndrome
b) nephritic syndrome?
a) Normal
b) Gammied
What are people with nephrotic syndrome at increased risk of?
Cardiovascular disease
Infection
How does the presentation of GN differ from that of interstitial nephritis?
Shouldn’t see proteinuria, haematuria on dipstick
As glomerulus isn’t involved
What is the cause of primary GN?
Idiopathic autoimmune disease
What are some causes of secondary GN?
Infections
Drugs
Malignancy
Vasculitis
Connective tissue diseases
What cells tend to proliferate when damaged in GN?
Mesangial cells
Endothelial cells
What is the difference between focal and diffuse GN?
Focal - < 50% affected
Diffuse - > 50% affected
How is glomerulonephritis treated with drugs?
Antihypertensive drugs - ACE inhibitors, ARBs, diuretics (also help with fluid overload)
Statins
then
Immunosuppression - IV steroids, azathioprine, antibody injections, biologic agents
How are people with nephrotic syndrome managed?
Oedema, so:
fluid restriction
salt restriction
diuretics
ACE inhibitors / ARBs
People with glomerulonephritis usually need ___ after symptomatic relief.
immunosuppression
Why are people with nephrotic syndrome at risk of infection?
Fluid overloaded, salty blood, oedematous
So adding immunosuppressants further increases infection risk
What is the commonest cause of nephrotic syndrome in children?
Primary GN - MINIMAL CHANGE GLOMERULONEPHRITIS
Does minimal change GN cause renal failure?
NO
What change is seen in minimal change glomerulonephritis?
Podocyte atrophy
What syndrome is caused by minimal change glomerulonephritis?
Nephrotic syndrome
How is minimal change glomerulonephritis treated?
Oral steroids
What is the commonest cause of nephrotic syndrome in adults?
Primary GN - FOCAL SEGMENTAL GLOMERULOSCLEROSIS
50% of people with focal segmental glomerulosclerosis develop ___ ___.
renal failure
Why can focal segmental glomerulosclerosis cause renal failure?
Widespread sclerosis which doesn’t resolve
What type of glomerulonephritis is caused by immune complex deposition in the basement membrane?
Membranous nephropathy
What are some causes of membranous nepropathy?
Infection
SLE
Malignancy
Drugs (remember gold and penicillamine used to treat CTD and are nephrotoxic)
Which antibody is associated with membranous nephropathy?
Anti-PLA2r antibody
What is the commonest form of glomerulonephritis?
IgA nephropathy
What is the common presentation of IgA nephropathy?
Haematuria after a viral infection
What type of vasculitis is IgA nephropathy associated with?
Henoch Schonlein purpura
purple, non-blanching rash on posterior thighs, abdominal pain, arthritis
What is seen on renal biopsy of IgA nephropathy?
IgA
Proliferation of mesangial cells
Which cells proliferate in IgA nephropathy?
What symptoms are produced?
Mesangial cells
Haematuria
What type of glomerulonephritis causes very rapid renal failure?
What diseases is it associated with?
Rapidly progressive glomerulonephritis (RPGN)
Small vessel vasculitis (ANCA positive)
Goodpasture’s syndrome
SLE
Henoch Schonlein purpura
(all ANCA negative)
How do ANCA positive vasculitidies cause RPGN?
ANCA activates neutrophils, causing inflammation
What derm presentation of vasculitis may be seen in RPGN?
Non-blanching purpuric rash
What is Goodpasture’s syndrome?
Type II hypersensitivity disease caused by production of autoantibodies for Type IV collagen
Where is Type IV collagen found?
Kidneys (glomerular basement membrane)
Lungs
Untreated Goodpasture’s syndrome causes which type of GN?
Rapidly progressing glomerulonephritis
How is RPGN treated?
Immunosuppression
In smokers / hypoxic presentation, renal failure and a vasculitic rash, suspect ___.
Goodpasture’s syndrome
causing RPGN
IgA nephropathy causes (nephrotic / nephritic) syndrome.
NEPHRITIC syndrome
The most common primary GNs tend to cause a nephrotic syndrome