Glomerular disease Flashcards
What is glomerulonephritis
Inflammation of or around the glomerulus and nephron
What can all forms of glomerulonephritis lead to
Nephritic / nephrotic syndrome
Different forms have tendency to cause one or the other or mixed
What are the features of nephritic syndrome
Haematuria
Red cell casts in urine (microscopic bleeding)
Hypertension
Mild to moderate proteinuria
Oliguria
What are the features of nephrotic syndrome
Massive proteinuria >3.5g/day
Hypoalbuminaemia
Oedema
Hypercoagulability
Hyperlipidaemia
Low total thyroxine levels
How does nephrotic syndrome predispose patients to thrombosis
Due to loss of antithrombin-III proteins and rise in fibrinogen levels
Why may low total thyroxine levels be seen in nephrotic syndrome
Due to loss of thyroxine binding globulin proteins
What are the symptoms of nephritic syndrome
Haematuria
Oedema (to a lesser extent compared to nephrotic syndrome)
Oliguria
Uraemic symptoms - fatigue, reduced appetite, pruritus
What are the symptoms of nephrotic syndrome
Facial oedema
Peripheral oedema
Frothy urine (due to heavy proteinuria)
Fatigue
Recurrent infections
Hypercoagulability -> MI / DVT / renal vein thrombosis
Why are patients with nephrotic syndrome predisposed to recurrent infections
Due to loss of immunoglobulins
Why is oedema more severe in nephrotic syndrome
Due to heavy loss of protein in urine causing hypoalbuminaemia.
Hypoalbuminaemia causes oedema because of reduced oncotic pressure so water goes out of blood vessels and into tissues
Clinical signs of nephrotic syndrome
Periorbital oedema / lower limbs oedema / Ascites
SOB due to pleural effusion
Xanthelasma due to hyperlipidaemia
Differences between nephritic and nephrotic syndrome
Nephritic syndrome causes haematuria, oliguria, hypertension whereas nephrotic syndrome does not
Nephrotic syndrome causes HEAVY proteinuria > 3.5 whereas proteinuria in nephritic syndrome is mild to moderate
Nephrotic syndrome causes more severe oedema
Nephrotic syndrome causes hyperlipidaemia and hyper coagulability whereas nephritic syndrome does not
What are the different types of glomerulonephritis
Minimal change disease
Focal segmental glomerulosclerosis
Membranous GN
IgA nephropathy
Post-infectious GN
Membranoproliferative
Rapidly progressive GN
Goodpasture’s syndrome
Alport’s syndrome
Which form of GN is the most common
IgA nephropathy
What are the types of GN regarding to its pathophysiology
Proliferative
Non-proliferative
What is proliferative GN
Presence of proliferation of endothelial and mesangial cells
Proliferative GN typically presents with
Nephritic syndrome
What is non-proliferative GN
Non-proliferative process.
Due to damage to podocytes
Non-proliferative GN typically presents with
Nephrotic syndrome
Which types of GN are non-proliferative
Minimal change
Focal segmental
Membranous GN
Which types of GN are proliferative
IgA nephropathy
Rapidly progressive GN
Anti-glomerular basement membrane antibody disease
Vasculitic disorders - GPA, MPA
Which types of GN can cause mixed- nephritic and nephrotic syndrome
Membranoproliferative GN
Post-Strep (infectious) GN
Minimal change disease is the most common
Most common cause of nephrotic syndrome in children
Causes of minimal change disease
Mostly idiopathic
What are the typical investigation results for minimal change disease
Highly selective proteinuria
NORMAL renal biopsy under light microscopy
NORMAL BP
Electron microscopy shows fusion of foot processes
What does highly selective proteinuria mean in minimal change disease
Only intermediate sized proteins such as albumin can leak through
What is special about minimal change disease
Normal light microscopy results
Abnormality only seen on electron microscopy
Management of minimal change disease
Oral corticosteroids (80% are responsive)
Cyclophosphamide for steroid-resistant cases
Salt restriction and fluid management
Describe the prognosis of minimal change disease
Relapse is common
1/3 have only 1 episode
1/3 have infrequent relapses
1/3 have frequent relapses which stop before adulthood
Focal segmental glomerulosclerosis is the most common
Cause of nephrotic syndrome in adults - young adults
Causes of focal segmental glomerulosclerosis
Idiopathic
Secondary causes
- HIV
- SLE
- reflux nephropathy
- sickle cell disease
- heroin
Typical investigation results for focal segmental glomerulosclerosis
On light microscopy - mesangial collapse and sclerosis
On electron microscopy - fusion of foot processes
Management of focal segmental glomerulosclerosis
Salt restriction and fluid management
Prolonged Steroids
Cyclophosphamide
Describe the prognosis of focal segmental glomerulosclerosis
60% go into remission with prolonged steroids
40% process into end stage renal failure after 10 years
Membranous glomerulonephritis mostly causes
nephrotic syndrome in adults (2nd most common cause)
Causes of membranous glomerulonephritis
Mostly idiopathic
Infections - Hep B, malaria
Malignancy - Prostate, lung, lymphoma, leukaemia
Drugs
SLE
Thyroiditis
What infections are associated with membranous glomerulonephritis
Hep B
Malaria
What malignancies are associated with membranous glomerulonephritis
Prostate
Lungs
Lymphoma
Leukaemia
What drugs are associated with membranous glomerulonephritis
Gold
Penicillamine
NSAID
Typical investigation results for membranous glomerulonephritis
Light microscopy
- thickened glomerular basement membrane
Immunofluorescence
- diffuse uptake of IgG
EM
- thickened glomerular basement membrane with sub epithelial deposits of immune complexes
What is the classic sign of membranous glomerulonephritis in EM
Spike and dome appearance due to subepithelial deposits
Management of membranous glomerulonephritis
all patients should receive ACEi / ARB
Steroids + cyclophosphamide
Describe the prognosis of membranous glomerulonephritis
Rule of thirds
- 1/3 spontaneous remission
- 1/3 chronic MGN
- 1/3 develop end stage renal failure
Membranoproliferative GN causes nephritic / nephrotic/ mixed syndrome
Mixed
Causes of membranoproliferative GN
Mostly idiopathic
Hep C
SLE
Typical investigation results of membranoproliferative GN
Thickened basement membrane
Thickened mesangium
Subendothelial deposition of IgG
What is the classic appearance of membranoproliferative GN
Tram tracking appearance due to deposits and thickened mesangium (mesangial cells disperse themselves between the basement membrane and endothelium as well)
Management of membranoproliferative GN
Steroids for children
Dipyridamole and aspirin for adults
Kidney transplantation for ESRF
Cause of IgA nephropathy
Due to mesangial deposition of IgA immune complexes
IgA nephropathy is associated with
URTI
Henoch Schonlein purpura
Dermatitis herpetiformis
Coeliac
Cirrhosis
What is the classic presentation of IgA nephropathy
Macroscopic haematuria in young people after a URTI
IgA nephropathy causes nephritic / nephrotic / mixed syndrome
Nephritic syndrome
Typical investigation results for IgA nephropathy
LM
- mesangial cell proliferation
Immunofluorescence
- IgA deposits in mesangium
EM
- deposits in mesangium
How long does GN occur after URTI in IgA nephropathy
1-2 days
Management of IgA nephropathy
If only haematuria and no/mild proteinuria
= no treatment, regular checkups
If persistent proteinuria
= ACEi/ARB
If GFR is falling / failure to respond to ACEi
= corticosteroids
Prognosis of IgA nephropathy
25% develop into ESRF
What are the markers of poor prognosis of IgA nephropathy
Male
Proteinuria
Hypertension
Smoking
Hyperlipidaemia
Which pathogen causes post-streptococcal glomerulonephritis
Streptococcus pyogene (group A beta haemolytic)
Post-streptococcal glomerulonephritis most commonly affects which age group
Young children
Post-streptococcal GN causes which type of syndrome
Mixed
Investigations for post streptococcal GN
Bloods
Renal biopsy
What do blood tests show in post-streptococcal GN
Raised anti-streptolysin O titre - confirms recent strep infection
low C3
What are the Renal biopsy results suggesting post-streptococcal GN
LM - Endothelial proliferation
EM- Lumpy immune complex deposits
Immunofluorescence - granular / starry sky appearance
Difference between post-streptococcal GN and IgA nephropathy
Post strep GN occurs 7-14 days after infection whereas IgA nephropathy occurs 1-2 days after infection
Post-strep GN causes low complement level
Post strep GN main symptom is proteinuria whereas IgA nephropathy is haematuria
Causes of rapidly progressive GN
GPA
MPA
Goodpasture’s
SLE
Rapidly progressive GN causes which type of syndrome
nephritic syndrome
Investigation results for rapidly progressive GN
Crescent formation in glomeruli (proliferating epithelial cells)
Management of rapidly progressive GN caused by goodpasture’s
high dose immunosuppression- IV methylprednisolone / cyclophosphamide
Plasmapheresis
Management of rapidly progressive GN caused by vasculitis
High dose prednisolone + cyclophosphamide
What is the defect in Alport’s syndrome
Defect in gene that codes for type 4 collagen causing abnormal glomerular-basement membrane
Alport’s syndrome is more severe in
Males
Mode of inheritance for Alport’s syndrome
Mostly X linked dominant
Symptoms of Alpert’s syndrome
Microscopic haematuria
Bilateral sensorineural deafness
Lenticonus - protrusion of lens
Retinitis pigmentosa
What is lenticonus
Protrusion of lens into the anterior chamber
What is retinitis pigmentosa
Progressive loss of photoreceptors + retinal deposits
Investigations of Alport’s syndrome
Genetic testing
Renal biopsy
What does renal biopsy show in Alport’s syndrome
Longitudinal splitting of lamina dense of glomerular base membrane
Basket weave appearance
