What is glomerulonephritis?
A group of mostly autoimmune inflammatory disorders affecting the glomeruli.
Classified by morphology they are responsible for 30% of End stage Kidney Disease cases
Other than autoimmune what can cause glomerulonephritis?
What are the two major syndromes associated with glomerulonephritis?
Nephritic Syndrome - Proliferative glomerulonephritis
Nephrotic Syndrome - Non-proliferative Glomerulonephritis
What are the major types of Glomerulonephritis?
- Post-infective nephritis
- IgA Nephropathy
- Focal Necrotising Crescentic Nephritis
- MEmbrano-proliferative nephritis
- Minimal change disease
- Focal & Segmental GN
- Membranous Nephropathy
How do we distinguish nephrotic from nephritic syndrome?
Nephritic syndrome involves Haematuria, proteinuria, hypertension and a low urine volume due to renal impairment.
Nephrotic syndrome involves hypoalbuminaemia, proteinuria, oedema and hyperlipidaemia. (basically glomeruli let albumin through)
What is the distinguishing feature of Nephritic syndrome?
Red cell casts in the urine.
These are made by nephrons and so only appear in glomerular damage
explain the presentation of nephrotic syndrome?
Hypoalbuminaemia due to leaky glomeruli
Directly causes proteinuria as albumin gets into urine
Oedema occurs because theres not enough albumin in blood to osmotically keep water from moving into the Extra-vascular compartment
Hyperlipidaemia because liver over produces albumin to compensate and produces more lipids as a side effect
Also raises risk of thrombosis and infection
What do diffuse, focal, global and segmental mean in terms of glomerulonephritis?
Focal affects <50% of the glomeruli
Global affects 100%
Diffuse affects >50%
Segmental only affects specific parts of the glomerulus
What are the types of proliferative glomerulonephritis?
Post-infective Nephritis (diffuse)
IgA nephropathy (Focal)
Focal Necrotising Crescentic Nephritis (FNCN)
What causes post-infective nephritis?
Mostly group A streptococci, it occurs 10-20 days post- skin/throat infection
Associated with genetic predisposition (HLA-DR or HLA-DP)
How do treat nephritic syndrome?
Amlodipine vasodilator for hypertension
Loop diuretics if theres oedema
What is the commenest cause of glomerulonephritis worldwide?
Its most common in teens/20s & men
Describe the pathogenesis of IgA nephropathy
IgA deposited in mesangium along with mesangial proliferation
How severe is IgA nephropathy?
Can be very minor with just microscopic haematuria
Or very severe with IgA crescentic GN leading to kidney failure within weeks
How does Focal Necrotising Crescentic Nephritis (FNCN) look?
A crescent of cells & Debris fills the bowman’s Space on biopsy.
It causes crazy high creatinine (~1200)
What are the classes of FNCN?
1) ANCA associated including wegener’s & microscopic polyangiitis
2) Anti-GBM (Glomerular Basement Membrane) incl anti-GBM nephritis and goodpasture’s syndrome
3) Others e.g. IgA vasculitis, post infective or SLE
How do you tell apart Anti-GBM FNCN
Anti-GBM antibodies can be found in the serum & kidney
May feature lung haemorrhage
How do you treat Focal Necrotising Nephritis?
With aggresive immunosuppression:
- High dose steroids
- Plasma Exchange
B Cell Therapy - Rituximab
What are hte types of non-proliferative glomerulonephritis?
1) Minimal change disease
2) Focal & Segmental GN
3) MEmbranous nephropathy
Who is most affected by minimal change disease?
Its the most common form in children
What characterises Minimal change disease?
Sudden onset oedema
How do we treat minimal change disease?
If they relapse use steroids again, concurrent relapses use other treatments like cyclophosphamide, tacrolimus or rituximab
How do you differentiate focal & segmental GN from other non-proliferative Glomerulonephritis’?
Well for starters its focal so <50% of glomeruli and segmental so only affects certain parts of the glomerulus.
How do you treat Focal &Segmental GN?
Trial steroids (often resistant) Cyclosporin, cyclophosphamide & Rituximab
Whats the commenest cause of nephrotic syndrome?
Membranous nephropathy in adults or Minimal change disease in kids
What causes Membranous nephropathy?
Secondary to Malignancy, SLE, rheumatoid arthritis or drugs (NSAIDs/gold/penicillin)
How do you tell membranous nephropathy apart?
Also primary membranous nephropathy shows serological markers (PLA2R antibodies & THSD7A)
How do you treat membranous nephropathy?
Just use general anti-nephrotic syndrome treatments for the 1st 6 months as 1/3rd of cases resolve on their own.
Immunosuppression (Monthly alternation of cyclophosphamide & Steroids for 6 months)
What general measures do you use to treat nephrotic syndrome?
Na/fluid restriction + loop diuretic for oedema Statin for hyperlipidaemia Pneumococcal vaccine for infection risk Heparin/warfarin for thrombosis risk RAAS blockage for hypertension
Cases in powerpoint
There are two categories of glomerulonephritis:
Proliferative & Non-proliferative
They are associated with nephritic (haematuria, hypertension & renal impairment) and nephrotic syndrome (proteinuria, oedema, hypoalbuminae & hyperlipidaemia) respectively.
There are a number of causes within each category but mostly they are autoimmune in origin (barring post-infective and membranous which can be secondary to malignant, drugs, R arthritis & SLE).
Treatment revolves around solving the problems/risks associated with nephritic/nephrotic syndrome and steroids/immunosuppression with mainly cyclophosphamide.