Clinical Aspects of Glomerular Disease (Glomerulonephritis) Flashcards
What is glomerulonephritis?
A group of inflammatory disorders of the kidney
How are the different sub-types of GN classfied?
Via their morphology
Describe nephrotic syndrome.
Massive loss of protein via urine = Hypoalbuminaemia - this is due to leaky glomeruli
Hypoalbuminaemia leads to oedema and hyperlipidaemia
Urine looks frothy
Why does Hypoalbuminaemia cause oedema and hyperlipidaemia?
Oedema - loss of albumin causes a reduced intravascular oncotic pressure which causes fluid to leak out of vessels and into surrounding tissue
Hyperlipidaemia - low albumin causes liver to increase albumin production in order to compensate BUT this also leads to increased production of lipids
Describe nephritic syndrome.
High levels of blood in urine
Increased levels of protein, but not as high as in nephrotic
Mild hypertension
Low urine volume due to reduced renal function
What type of glomerulonephritis causes nephrotic syndrome?
Non-proliferative glomerulonephritis - such as minimal change, membranous, focal segmental and Membranoproliferative (not sure about this one)
What type of glomerulonephritis causes nephritic syndrome?
Proliferative glomerulonephritis - such as:
IgA
Cresent/rapidly progressive
Post-streptococcal/post-infective
What do diffuse, focal, global and segmental mean in terms of glomerulonephritis?
Focal affects under 50% of the glomeruli
Diffuse affects over 50%
Global affects 100%
Segmental only affects specific parts of the glomerulus
Differentials for nephrotic syndrome?
Congestive heart failure
Hepatic disease
Name the proliferative subtypes again and name which ones are focal and which on is diffuse.
IgA - focal
Post Infectiive - diffuse
Crescentic/Focal necrotizing/rapidly progressive - focal
Membrano-proliferative
Describe the presentation of post-infective GN.
Follows 10-21 days after infection of throat or skin
Patient will be generally unwell and have dark urine
Might have puffy face
Might have higher BP
Most common type of bacteria causing post-infective GN?
Lancefield group A streptococci
Does post-infective GN have a genetic predisposition?
Yes
Treatment for post-infective GN?
Loop diuretics IF there is oedema - frusemide
Vasodilators for mild hypertension - amlodipine
Antibiotics are debatable
Most commonest cause of GN ?
IgA nephropathy
Pathogenesis of IgA GN?
IgA is depositied in mesangium causing mesangial proliferation (see Dr P Browns lecture for more)
How will IgA present?
As a nephritic syndrome but with microscopic blood in urine with maybe some protein present in urine also
IgA investigations?
Biopsy will show IgA deposits
IgA GN treatment?
Steroids or cyclophosphamide if reduced renal function - support for transplantation
Otherwise just support symptoms, like hypertension with hypertensive therapy (ACEIs)
What is the outcome for IgA?
20% ~ reach ESRD in 20 years
Outcomes for post infective?
95% of children make full recovery
The rest could go on to develop crescentic/ rapid progressing GN
Describe Cresentic GN.
Most aggressive type and can lead to ESRD in days
What does crescentic look like pathology wise?
A crescent shape of cells fills the bowmans space
What does crescentic GN do to creatinine levels?
Increases them greatly
What is anti-GBM?
Anti-glomerular basement membrane also known as goodpastures
A type of crescentic GN causes by anti-GBM (glomerular basement membrane)
What % of crescentic GN is anti-GBM?
10-20%
How does anti-GBM present?
Nephritis
Haematuria and haemoptysis
What causes the haemoptysis in anti-GBM?
A CxR will show infiltrates
How is anti-GBM diagnosed?
Anti-GBM antibodies in serum and kidney will be detected
Treatment for anti-GBM?
Agressive immunosuppression - steroids, plasma exchange, cyclophophamide
How is crescentic GN managed?
Same as anti-GBM
Immunosupression
Name some ways to immunosupress.
Steroids Cyclophosphamide Plasma exchange B-cell therapy Complement inhibitors
Crescentic prognosis?
Good if treated early
Summarise proliferative GN.
Presents with nephritic syndrome
Blood on dipstix with variable proteinuria
Can cause rapid decline in renal function –> dialysis
Early diagnosis and treatment = good prognosis
What actually is the main difference between proliferative and non-p?
P - Excessive numbers of cells in glomeruli. These include infiltrating leucocytes
Non-P = Glomeruli look normal or have some areas of scarring. Normal no. of cells
Name again the types on non-p GN?
Minimal change
Membranous
Focal and sentimental
Membranoproliferative (not sure again if this is P or NP)
How do we generally manage nephrotic syndrome?
Treat oedema via loop diuretics/salt and fluid restriction
Treat hypertension - RAAS blockade
Treat hyperlipidaemia - statins
Reduce risk of thrombosis - Heparin/Warfarin
Reduce risk of infection - pnumonococcal vaccines
What is the commonest cause of nephrotic syndrome in children?
Minimal change GN
Describe the onset of minimal change GN.
Sudden onset of oedema within days
Treatment for minimal change GN?
Steroids - prednisolone until remission is achieved then slowly taper off
2/3rds of patients relapse so treat this with a further steroid course
Any further relapses trat with cyclophosphamide
Minimal change prognosis?
Despite replases prognosis is good and risk of ESRD is low
Steroid toxicity risk is high depending on exposure
Describe focal and segmental GN.
Is not a single disease but a syndrome with multiple causes
Can be 1y - idiopathic - or have a 2y cause
Presents with nephrotic syndrome
High chance of progression to ESRD
What does the pathology show for focal segmental GN?
Reveals focal and segmental sclerosis with distinctive patterns
Is steroids a good treatment for FS GN?
No as it is generally resistant to steroids
Treatment for FSGN?
General measures to handle symptoms - hypertension, hyperlipidaemia, oedmea, and anti-coagulants
Trail steroid treatment - even if it partially works it still improves prognosis
Could try cyclophosphamide, cyclosporin etc
What is the commonest cause of nephrotic syndrome in adults?
Membranous nephropathy
What causes the majority of membranous GN cases?
Occur in isolation - idiopathic
What are the serological markers for membranous GN?
Anti-phospholipase A2 receptor antibody
Thrombospondin type 1 domain containing 7A
2y causes of membranous GN?
Malignancy
SLE
Rheumatoid arthritis
Drugs - NSAIDs, gold, penicillamine
Treatment for membranous GN?
General measures for ~6 months
Immunosuppression if symptomatic nephrotic syndrome - rising proteinuria/deteriorating renal function
Cyclophosphamide and steroids, alternate months for 6 months
Cyclosporin
Rituximab - b-cell therapy
Prognosis of membranous GN?
Resolves in 1/3 of patients
Prognosis good if treatment controls the proteinuria
BUT
~25% end up on dialysis in 10 years and it can reoccur even after transplantation
Summarize the key points for non-proliferative GN.
Presents as nephrotic syndrome
Renal biopsy is a key investigation
ID the cause and treat it if 2y
General measures to control symptoms are important in all cases
Specific treatment should be tailored to the type of GN
